1

Copyright © 2016 and Beyond.

All rights Reserved No portion of this book may be used, reproduced, or transmitted in any

form or by any means, electronic or mechanical, including fax,

photocopy, recording, or any information storage and retrieval system by

anyone but the purchaser for their own personal use. This manual may

not be reproduced in any form without the express written permission of

Brad Pilon, except in the case of a reviewer who wishes to quote brief

passages for the sake of a review written for inclusion in a magazine,

newspaper, or journal, and all of these situations require the written

approval of Brad Pilon prior to publication.

The information in this book is for educational purposes only. The

information in this book is based on my own personal experiences and

my own interpretation of available research. It is not medical advice

and I am not a medical doctor.

The information within this book is meant for healthy adult individuals.

You should consult with your physician to make sure it is appropriate for

your individual circumstances. Keep in mind that nutritional needs vary

from person to person, depending on age, sex, health status and total

diet.

If you have any health issues or concerns please consult with your

physician. Always consult your physician before beginning or making any

2

changes in your diet or exercise program, for diagnosis and treatment of

illness and injuries, and for advice regarding medications.

3

Introduction

Bacteria. The very word makes me think of runny nosed little

children and sneezing and coughing. Bacteria make us sick - plain and

simple.

Yet, the beer I drink would not exist without bacteria, neither would the

bread or butter on the table in front of me.

My background is in nutrition – I’ve been studying nutrition for over two

decades; first as a student, then as a graduate student, then finally as an

author. I know if we are going to help people live longer lives, it is going to

take radical changes in lifestyle, giant advancements in medical science,

and by broadening our understanding of human nutrition.

After listening to visionaries like Aubrey Degray talk passionately about

using the power of bacteria to create optimal health and extend human

life, I have begun to realize that the microcosm – the trillions upon trillions

of microorganisms that inhabit this earth, are a lot more important to

optimizing human health than I had previously realized.

Interestingly - lifestyle, environment, medicine and nutrition all can affect

the microscopic life forms that live in our guts, and these life forms can

influence our metabolism and change the very way our bodies work.

4

Surprisingly, the bacteria in our guts are very responsive to the food we

eat, and these responses happen extremely quickly. A recent study

published in Nature has shown that changes in our diet can cause

changes in the bacteria that live in our gut, changes that are easily

measureable within three or four days1.

With this connection in mind I began to research on the possible

connection between nutrition, our gut bacteria and our health. However,

‘health’ is an incredibly broad topic, so I decided to concentrate on one

of the largest health epidemics in human history - obesity. Specifically, I

was exploring the idea that our gut bacteria are somehow connected to

our ability to gain, and lose weight.

My goal was to answer two seemingly simple questions:

1) Could bacteria be helping to make us fat?

2) Could bacteria help make us thin?

Over four years of research later, it is now apparent to me that the

microorganisms in and around our bodies are not only the building blocks

of all life on earth, but also occupy an indispensable role in human health.

In fact, I’m now convinced improving the interaction between what we

eat, the environment we live in and the microorganisms in our body will

one day play a role in curing obesity. The major flaw in weight loss

research is that it largely ignores this single fact – We do not ‘feed the

machine’ as people like to say; we ‘feed the machines that then feed us’.

These ‘machines’ are actually a highly complex network of trillions of

5

microorganisms that live in our guts. If you keep these microorganisms

happy and healthy then there is a greater chance that you will be happy

and healthy, but if they become even a little unhealthy, it paves the way

for obesity and a whole host of life-ruining diseases.

There are dozens of books written about how to eat to keep your gut

bacteria healthy, but of the books I reviewed they all omitted large areas

of research, including the effect that our environment has on our gut

bacteria.

Many also glossed over what I feel is the most immediate danger of an

unhealthy gut, and that is the toxins that can be formed by our gut

bacteria and released into your body, toxins that are associated with the

development of many diseases, including obesity.

In the following pages you will discover the connection between what

you eat and the bacteria living in your gut, and how they influence your

health and your ability to lose weight.

6

Gut Bacteria

Your ‘gut’ includes trillions of living microorganisms working in

harmony with your immune system, nervous system and hormonal system

to regulate your metabolism, physiology and health.

Most microorganisms that live in your gut play a beneficial role in

maintaining your health. As a group these microogragaisms consist of

bacteria, fungus and even spores. Collectively they are called your

microbiotia, microbiome or microflora; however, it’s much more common

to simply refer to them as your ‘gut bacteria’.

Our gut bacteria protect us against dangerous pathogens2,3, they also

help extract nutrients and energy from the food we eat4,5, and they are

essential for a healthy immune system.6 They can also produce toxins that

push us towards atherosclerosis7, diabetes8 and obesity9.

Our gut bacteria vary depending on our age, gender, diet, exercise

choices, geography, hygiene, stress (both physical and mental)

medication use, birthing method (whether you were born via a c-section

or vaginal delivery) and the foods choices you were first given as an infant

(breast milk vs formula). You inherited most of the initial microbes from

7

your mother, but other bacteria are picked up from your environment.

The science behind gut bacteria is very complex. Sure, some people may

make it sound like we have it all figured out, but we’ve only truly begun to

scratch the surface of understanding how our gut bacteria interact with

our bodies.

As an example, to date, we have not discovered all of the bacteria that

live in your gut. Of the bacteria we have discovered, we’re still not sure of

their exact role in our health. We know there are families of bacteria like

Bacterioidetes and Firmicutes, and that they are generally associated with

health and disease, and different types of diets, but to say we know their

exact role would be extremely premature. The best we can do is

summarize what we do know:

A gut that is unhealthy tends to have a ‘low richness’ of gut

bacteria. This is called ‘dysbiosis’. Having an unhealthy gut can lead

to inflammation, insulin resistance, obesity and a whole host of

diseases.

A gut that is healthy is said to have ‘high richness’ of gut bacteria

and is associated with health and protection against weight gain.

The overall richness of your gut bacteria can be influenced by many

different factors: Overeating and the typical western diet high in

processed foods, fats and sugars, can cause a dysbiotic gut, or a gut with

low richness. This lack of richness can also be caused by many different

environmental factors that we will touch on later in this book.

8

The evidence suggests that while our gut bacteria is highly influenced by

what we inherited from our mothers and from the foods we customarily

eat, it also suggests that our gut bacteria is under attack daily, and that

the accumulating damage from these attacks can led to a low gut

richness which can leave you prone to weight gain. Luckily, this problem

can be combated through diet and is directly associated with weight loss.

9

Gut Bacteria and Your Health

At least 70 million people in the U.S. suffer from some sort of

digestive illness, and stomach and digestive problems are said to account

for nearly 10% of all healthcare spending.10

In medicine and nutrition, the word ‘gut’ usually refers to our stomachs

and intestines. Up until recently, ‘digestion’ was simply the combination of

chewing your food, then having the acids and enzymes in your stomach

break down your food.

This overly simplistic view of how we handled our food was accepted

because initially the belief was that the digestion process really did not

require bacteria at all, and that any bacteria detected were simply

transient – introduced to your gut when you ate improperly washed foods.

In fact, bacteria were viewed as the enemy, an enemy that needed to

be eliminated in order to prevent illnesses and restore health. Increasingly

powerful weapons in the form of disinfectants, antibiotics and food

preservatives were created to fight the imagined health-robbing bacteria

that plagued our foods and our kitchens.

We washed countertops, hands, utensils and even our foods with

10

disinfectants and anti-bacterial agents, then added preservatives to

prevent any future bacterial growth and to keep the food from going

bad. We did everything in our power to make sure we were ‘bacteria

free’.

However, this was an error in judgment and the war on bacteria led to an

attack not only on truly ‘bad’ bacteria (such as salmonella and other

bacteria that cause food poisoning), but also on the good bacteria – the

bacteria that are absolutely essential to human health. This is the bacteria

you literally cannot live without.

A healthy gut is a gut that is full of good microorganisms acting like a

fermentation tank inside of your body. It is constantly orchestrating

complicated chemical reactions with the foods you eat that your body

simply cannot do on its own.

They survive on food that passes through our bodies, creating energy from

the parts that we cannot digest ourselves. They occupy space along our

intestinal walls where disease-causing pathogens might otherwise attach

themselves; they also produce substances that protect against invading

pathogens and behave as low-level antigens, inducing intestinal

lymphatic tissues to churn out natural antibodies that prevent ‘bad’

bacteria from invading.

The bacteria in your gut are continually reading the environment and

responding – they can communicate with one another and adapt very

quickly. Bacteria can trade DNA almost in the same way we trade text

messages, picking the pieces of information they need and sharing it with

their friends to improve the outcome of their community, doing their

11

absolute best to not only change and adapt to the new environment at a

speed far greater than we could ever accomplish on our own, but to also

directly cause changes in the rest of your body too.

These microorganisms aren’t only responsible for helping you absorb the

nutrients in your food, they can also influence many of your brain

neurotransmitters affecting your learning abilities, memory, sense of

hunger, and stress responses.11 They may not be in control, but they are

definitely silent co-pilots.

They are also integral in managing inflammation levels within your body,

and chronic low-grade inflammation has been identified as a link

between many diseases associated with obesity.12

They can alter hormone levels and how your body reacts to these

hormones, including many of the hormones that are responsible for

bodyweight regulation, such as insulin13, ghrelin14 and leptin15. It has even

recently been discovered that your gut bacteria may hold an influence

over your metabolic rate.16

In other words, when working properly your gut bacteria do everything in

their power to keep you healthy and free of disease. In this sense, our

relationship with our gut bacteria could be considered highly

cooperative. When functioning properly, our gut bacteria keeps our

bodies and metabolisms healthy as long as we keep feeding them the

foods they like to eat.

The human/microorganism interaction is so important to the future of

health and nutrition that there are multiple long-term large-scale studies

12

going on right now to try and decode our microbial blueprint.

The Human Microbiome Project and the European Metagenomics of the

Human Intestinal tract are multi-million dollar research initiatives that have

made substantial progress in helping us understand the symbiotic

relationships between our gut microbes and our health.17,18

It is the recent advancements in these studies and others like them that

have finally shed light on the other important role that your gut bacteria

plays in your health, the prevention of weight gain, and conversely how

having sick or dysfunctional gut bacteria (dysbiosis) could very well be a

silent factor of obesity that until now has largely been ignored.

13

When Bacteria Go Bad

I mentioned earlier that Aubrey De Gray was the first person I ever

heard who suggested that optimal human health could be derived from

bacteria, but he certainly wasn’t the first to make this suggestion.

Nobel Prize winner Ilya Mechnikov was the first to propose the use of live

bacteria to maintain bowel health and prolong life, and he did so before

the end of the 19th century. Surprisingly, even though the idea has been

around for over a century, it has only been in the last decade that

research has really begun to unravel the startling connection between

the bacteria in your gut and your health, and now your ability to gain and

lose weight.

Culture-based studies suggest that all healthy adults share most of the

same gut bacterial species — a core set of gut bacteria essential to

proper human digestion and overall health.19

Humans and animals who have been stripped of their gut bacteria quickly

get sick and see a whole host of growth and health problems, so this base

set of gut bacteria is essential to our health.

14

Yet, despite the consistency of this core group of bacteria, the relative

proportions and the different types of species present can vary between

individuals, and within the same individuals at different points in their lives.

In other words, while the basic make up of our bacteria is very similar,

there can be striking differences in proportions of bacteria species, and

even differences in the species themselves from person to person.20

In fact, entire populations of people can be separated by the differences

in their gut bacteria. For example, Italian children have different bacteria

than children from rural Africa, and both children and adults from the

United States have very different bacteria from populations in Malawi and

the Amazonas state of Venezuela.21,22

Your gut bacteria can vary not only because of where you live and what

you typically eat, but also as a consequence of changing environmental

factors, such as stress, exercise, or even travel. Sometimes these variations

protect you against gaining weight and from falling victim to several

different diseases, but other times the variations hurt you and cause

dysbiosis.

Dysbiosis usually begins when your gut bacteria begins to disproportionally

favor one type of bacteria over another. Instead of being a healthy blend

of bacteria, one particular group starts to take over. This is what it means

to have a ‘low richness’ of gut bacteria.

Low richness of gut bacteria has been reported in patients with

inflammatory bowel disorder (IBD)23,24,25, people suffering from chronic

fatigue syndrome26, and has also been reported in the elderly with

inflammation27 and people who are overweight28 and has even been

15

linked to diseases like Multiple Sclerosis29 and Autism30.

It’s often said that ‘before obesity comes inflammation and before

inflammation comes gut dysfunction’ and in this case I couldn’t agree

more.

It seems that the bacteria in your gut are central in helping to regulate

inflammation in your body, and when inflammation goes unchecked

because of dysbiosis, your entire immune system begins to crack under

the immense pressure of trying to maintain your health.

This is not to say that obesity happens in a vacuum, or that gut bacteria is

solely the cause of obesity. Rather, the alterations in gut bacteria, the

toxins they release, and the effects they have in your body are all part of

the cascade of events that lead to obesity, and they are tied to the

effects of overeating.

One of the jobs of your gut is to allow the essential building blocks for your

body to enter into your body by passing through the lining of your gut and

entering into your circulation, while at the same time making sure that

nothing dangerous gets into your body.

Basically, it is constantly picking out the good pieces from a sea of bad

pieces. But when dysbiosis and inflammation begin to set in then

Hyperpermeability follows – Hyperpermeability (Often called leaky gut) - is

the beginning of many illnesses.

16

Hyperpermeability and Endotoxins

Hyperpermeability is now suspected to be a crucial element linking

obesity to obesity-related diseases such as type 2 diabetes and even

some forms of cancer.

Hyperpermeability, also known as a leaky gut, is exactly what it sounds like

– the walls of your gut are compromised and things that would otherwise

never make it into your circulation now begin to ‘leak’ in.

The idea of a ‘leaky gut’ used to be very controversial, once only

believed to be an actual phenomenon by alternative health practitioners.

These days it is a widely accepted physiological condition.

This ‘leaking’ and altered bacteria have been found in cases of

irreversible diabetes due to its ability to cause disruptions in the immune

system that converge to promote something called ‘autoimmune islet cell

destruction’ which is the beginning of irreversible diabetes.31,32

A leaky gut has also long been linked to ulcers, inflammatory bowel

disease33, chronic liver disease and the promotion of certain types of

cancer34. And while a leaky gut is definitely not something you would ever

want, it’s not the only way gut dysbiosis can negatively affect your health.

Lipopolysaccharide (LPS), is what scientists call an endotoxin - a toxin that

17

in certain cases is released by bacteria into your gut. When these

endotoxins are able to enter your body through your leaky gut they can

cause chronic low-grade inflammation, and ultimately insulin

resistance.35,36

Endotoxins secreted or created by dysbiosis have also been linked to the

development of atherogenesis37, rheumatoid arthritis38, and even

depression39.

When endotoxins from your gut are able to enter your blood stream it

creates a condition called endotoxemia. At its worst, endotoxemia can

lead to septic shock if the immune response is severe enough.40 However,

even at low levels endotoxemia is dangerous as it is now being associated

with insulin resistance and the development of obesity.41

Basically, when your gut bacteria are unhealthy and dysbiosis occurs, your

bacteria can produce toxins. Then because of the hyperpermeability of

your gut, these toxins can enter your body and push you towards insulin

resistance and weight gain42, especially after a meal that is high in both

sugars and fats43. In fact, endotoxemia is directly related to calorie intake

- the more you eat, the higher the risk.44

Studies now demonstrate that even low levels of metabolic endotoxemia

may initiate an inflammation response which predisposes people towards

weight gain and may also eventually cause insulin resistance and even

full onset diabetes.45

To summarize, your gut can compromise your health through a cascade

of events. A dysbiotic gut can create a leaky gut, which can then lead to

the movement of endotoxins into your body after a high-carbohydrate,

18

high-fat meal, resulting in endotoxemia and low-grade inflammation.

However, not all of these events have to happen for your gut to affect

your metabolism, your hormones or your health.

Each of these scenarios has the ability to lead to an altered metabolism,

and contribute to the deleterious effects that create the ‘perfect storm’

for the development of unwanted weight gain and obesity46, a perfect

storm to which many of us have fallen victim.

We’re quick to blame our diet, or our genetics, yet research has very

clearly illustrated that a dysbiotic gut, and all the negative health effects it

is associated with, are not necessarily caused by poor diet choices,

genetics or even a lack of exercise.

19

It Might Not be Your Diet’s Fault

There is no doubt that obesity has become a worldwide health

concern. Since the early 1950s we have been attempting to solve obesity

as a national priority. However, our attempts have been met with very

limited success.

Despite decades of education, diets, exercise programs, and the rise of

billion dollar industries like the supplement industry and weight loss

industry, we still have not cracked the obesity code.

It is very evident that something about the modern western lifestyle is at

the heart of the problem. In addition, it is also evident that there is some

genetic control over how susceptible a person is to gaining weight over

their lifetime.47

Yes, food is to blame. Food is what our fat is made of, and it’s easy to see

that as a population we eat more than we need to. But blaming food

outright is a lot like blaming an abundance of bricks for a house being too

large.

When you force groups of people to overeat in scientific studies, it’s no

surprise that they all gain weight, but what is surprising is the large

variability in how much weight is gained.

20

Some people may gain 3 or 4 pounds, while some gain over 10 pounds in

the same time period.48

In fact, even in studies where identical twins are forced to overeat there is

a difference in how much weight and fat is gained between each

identical twin.49

The basics of gaining and losing weight are well understood. We know

that people are capable of gaining weight, and we know that there is a

large degree of variability between people when it comes to how much

weight they gain.

We also know that everyone is capable of losing weight, but again there

is a large degree of variability between people when it comes to how

much weight they can lose in a given period of time and how easily they

lose that weight.

However, beyond these rather basic premises, weight loss and weight

gain become much more complex.

Surprisingly, much of what we thought to be true about weight gain is

actually false. As an example, obesity researchers have discovered that

people who are overweight are not ‘lazy’ like many people believe.

In studies comparing obese areas of North America with non-obese

hunter-gatherer tribes, they found that the amount of energy expended

between the two populations was very similar.50 In other studies

comparing the energy expenditure of people of different body weights

and body fatness from all around the world it was found that there wasn’t

21

much difference in the amount of energy an obese person expends in a

day versus that of a lean person.51

The point is that people don’t become overweight simply because they

are lazy and don’t take enough steps in a day.

We’ve also discovered that while it is true that people who are overweight

do typically overeat, it’s not nearly to the extent that many people think

they do. From our best guesses the amount of food people eat per day

has increased by over 400 calories since the 1970s.52

To be clear, 400 extra calories a day is enough to cause weight gain in

anyone, but it does not explain the large variability in the amount of

weight people gain over a similar period of time while eating similar

amounts of food. And this is what we are truly concerned with – the

possibility that the variability of weight gain is influenced by factors other

that overall calorie intake. Or, why some people seem to be protected

against gaining weight while others are extremely susceptible to it.

Everyone gains weight, and everyone loses weight. The puzzling question

is why is there such a wide range in how much weight some people can

gain or lose? The easy answer is that it’s a lack of self-control or that

people are simply lying about how much they eat. Yet, this same

variability happens in well-controlled scientific studies – Studies that not

only control how much people eat, but also how much exercise they do.

The truth is, if weight gain was simply a mathematical equation of calories

in and calories out, we would be able to estimate weight gain with

amazing accuracy – but we can’t. We can estimate, but our precision is

severely lacking. This fact begs the question - if weight maintenance is

22

truly calories in and calories out then this raises the question – Calories in

and calories out…of what?

Calories don’t count just because they’ve entered your mouth; they only

count once they’ve entered your body. This is where the bacteria in your

gut bacteria can exert an influence over how much weight you will gain

and how quickly you gain it or lose it. They are the middle, the black hole

between the point food enters your mouth and when the nutrients (and

energy) from these foods enter your body.

After all, when you eat food, it is your gut bacteria that you are feeding

first. Once they have taken the energy they need to survive they then

feed you.53 But even this is an overly simplistic statement. Your gut

bacteria also creates unique nutrients that are essential for proper human

health54 and make vitamins that you require but cannot make on your

own55.

It has even recently been discovered that gut bacteria is capable of

creating essential amino acids, amino acids previously thought to ONLY

be available through diet.56 Yet, our bacteria can make these amino

acids and then allow them to enter into your circulation.57

If weight gain is calories in and calories out of your system, the answer we

require becomes ‘What role does your gut bacteria play in this process?’

We know that there is a difference between the bacteria in a lean

person’s gut and the bacteria in an overweight person’s gut.58 We also

know that when an overweight person loses weight the diversity of their

bacteria improves.59

23

From animal studies we know that diets that promote weight loss also

promote improved gut bacteria richness, and that this improvement isn’t

solely due to the weight loss caused by these diets, as mice fasted for as

little as 24 hours show a improved bacteria richness.60 Finally, we also

know from animal studies that when you take the bacteria from an obese

animal’s stomach and put it in a lean animal’s stomach the lean animal

starts to become obese (and vice versa).61

This research clearly shows there is a link between your ability to maintain

your weight and the type of bacteria that is in your gut. When you

improve the health of your gut bacteria weight loss occurs; when you gain

weight the health of your gut bacteria worsens. In fact, it’s more than just

a link. There is a direct correlation between the health of your gut

bacteria and your weight.

An abundance of calories is part of the cascade that leads to obesity,

and so is the health of your gut bacteria. They are connected. However,

the connection is more than just calories. As we will see in later chapters

the quality of food also matters.

Knowing this connection, our next step is to investigate the major factors

that are able to change your gut bacteria, and they are as follows:

• Your diet,

• Your exposure to antibiotics, and

• Your exposure to environmental pollutants.

24

The Antibiotic Weight Gain Connection

Antibiotics are medicines used to treat infections or diseases caused

by bad bacteria. Probably one of the most well known antibiotics is

penicillin, but any product or compound that is able to kill bacteria is an

antibacterial agent.

Now, it is important to keep in mind that antibiotics can be lifesavers. If

you're sick with a bacterial infection, taking an antibiotic may be the

appropriate - and life-saving- course of action. However, the unfortunate

side effect of antibiotics is that they may be playing a much bigger role in

our obesity epidemic then we ever could have imagined.

As we discussed earlier, the composition of the bacterial communities in

your gut are generally considered to be stable, but this stability can be

altered by antibiotic therapy7,62. For example, a one-week treatment with

antibiotics has been shown to alter gut bacteria for up to 4 years.63

Further studies support this finding showing one-week of antibiotic use

changing gut bacteria for 2 years after treatment.64 Antibiotics use, and

their profound affect on our gut bacteria richness could very well be a

missing link that helps explains why obesity is known as a disease of the

‘western industrialized world.’

25

Antibiotic use is ubiquitous in industrialized countries - at some point in their

lives people who live in industrialized countries have been on antibiotics,

and what is less obvious, they are probably being exposed to antibiotics

right now.

Children in North America receive, on average, between 10 and 20

courses of antibiotics before they turn 18. And antibiotic use in early

childhood may be able to affect the richness of your gut bacteria,

leading to an increased risk of becoming overweight later in life.65

Interestingly, much of this anti-biotic use may be in error, as research now

suggests that up to half of all antibiotic prescriptions may be

unnecessary.66

Within the United States of America, the States that have the highest use

of antibiotics also have the highest rates of obesity67. This could be

explained by suggesting that obese people need more antibiotics than

lean people; however, it also could be that the antibiotic use is directly

adding to the development of obesity.

This suggestion is supported by the research showing that when adults are

given antibiotics it rapidly alters their gut bacteria, and that their gut

bacteria STAYS altered for long periods of time.68 So even though anti-

biotic use may not immediately lead to weight gain, it may do so over the

years following their use.

A 2013 New York University study found that antibiotic use in the first six

months of life was linked with obesity later on. In this study, scientists

looked at statistical data collected from nearly 11,000 children in Avon,

26

England. The researchers found that children who were given antibiotics

in their first six months had a higher incidence of obesity later in life,

supporting the idea that while the effects may not be immediate, they

could still be contributing to weight gain years, even decades later.69

Finally, we have a research study that showed when 48 subjects were

given antibiotics, there was a definite increase in their weight during their

treatment, suggesting that, at times, the results can be much more

immediate.70

The bottom line is that antibiotic use alters your gut bacteria, and your gut

bacteria can either protect you from, or lead you towards obesity. In the

future, we may actually use targeted antibiotics in a positive way to

influence your gut bacteria, but we are years away from the possibility of

using antibiotics as an obesity treatment.

Interestingly, even if you have never taken any antibiotic treatments in

your entire life, they could still have dramatic and long lasting affects on

your ability to lose weight.

27

Antibiotics are Everywhere

It is estimated that Americans take more than two times the amount

of antibiotics than necessary. And while this fact alone is concerning,

medical prescriptions are not the only way we are exposed to antibiotics.

Scientists have found antibiotic residues in meat, milk, chicken, shrimp71,

ready-to-eat salads72 and even some herbal supplements.73

Surprisingly, even organic foods are not immune to the reach of

antibiotics. Until recently, antibiotics were even used on some organic

fruits and vegetables.74

The reason antibiotics are found in so many of the foods we eat is that

they act to kill any bacteria or funguses in foods that would otherwise

shorten a product's shelf life.

The food industry often calls them preservatives, but make no mistake -

they are antibiotics, preventing bacteria and molds from making a food

go ‘bad’.

While it may not surprise you that there are antibiotic residues in many of

the food we eat, it may surprise you to know that there are also

antibacterial components in many household products you are exposed

to on a daily basis (sometimes multiple times per day) like the antibiotic

28

Triclosan that is found in toothpaste and soaps.

In fact, Triclosan is an antibiotic added not just to toothpaste and soaps

but also to your clothing, kitchenware, furniture, highchairs for children,

and even toys. It also may be added to some cosmetics—products

regulated by the U.S. Food and Drug Administration (FDA).75

Many cleaning compounds contain hidden antibiotics – these

compounds have very long chemical names and they are often not

easily recognized as antibacterial agents on packaging labels.

A recent survey published in 2000 reported that 76% of liquid soaps from

10 states in the US contained Triclosan and approximately 30% of bar

soaps contained another type of antibiotic called triclocarban.76

Unbelievably, the safety of triclosan was never proven in a way that was

satisfactory to the medical community. Because of this, in September of

2016 the United States Food and Drug Administration (FDA) announced

that 19 antibacterial ingredients, including both triclosan and

triclocarban, must be removed from hand and body washes within one

year because manufacturers have failed to prove they are either safe or

effective.

Overuse and chronic exposure of Antibacterials can cause health

complications including cancer, antimicrobial resistance and endocrine

disruption. There are also studies linking chronic exposure of antibacterials

to obesity. Worst of all, they don’t even help clean anymore than

traditional soap and water. For these reasons my advice is to avoid

antibacterials whenever possible, and unless necessary.

29

Unfortunately, even if somehow you have managed to never take

antiobiotics AND you have avoided all of these products, the truth is

recent study results suggest that Triclosan is a previously unrecognized

contaminant of U.S. water nationwide, likely ranking in the top 10 in

occurrence rate and in the top 20 in maximum concentration of organic

pollutants.77

The bottom line is that we are surrounded by antibiotics and are exposed

to their residues on a daily basis. Even if you’ve never taken an antibiotic

medicine in your life, you (and your gut bacteria) are being exposed to

subclinical doses of antibiotics multiple times on a daily basis.

Most importantly this research shows that exposure may be affecting your

ability to lose weight. In a perfect world our gut bacteria would work

exactly the way it is supposed to, in perfect cooperation with the rest of

our body. Unfortunately for some of us, our bacteria have been

compromised due to the reasons explained above.

This is what I meant when I said that your gut bacteria is under attack on a

daily basis. Not only does the common western diet support a bacteria

that is low in richness, but constant exposure to antibiotics and

antibacterial chemicals through medicines, food, toothpaste, cosmetics,

and the water you drink may also affect your guts ability to return to a

healthy richness, instead maintaining it in a constantly compromised state.

As it turns out, our gut bacteria are highly responsive to our environment.

This responsiveness even includes airborne pollution, which is able to travel

from our lungs to our gut bacteria via mucosal transport.78

30

From Air to Gut

The world is seeing a dramatic rise in population growth in urban

areas. Our cities are getting denser, and with more people comes more

pollution.

We know about pollution, we talk about pollution and we have a general

idea that pollution is ‘bad for us’. What we don’t talk about - don’t even

want to think about - is that the air we breathe may be contributing to our

obesity problem.

Though research on airborne pollutants has mostly focused on

cardiovascular and respiratory effects, emerging evidence suggests air

quality and air pollutants are also having adverse effects in our guts.

Epidemiological studies have revealed an association between exposure

to air pollution and different gastrointestinal diseases including

inflammatory bowel disease and irritable bowel syndrome.79,80,81

If you are like me you are probably wondering how the heck can air

pollution affect our gut bacteria? After all, it’s not as if we swallow air all

day long!

To explain how pollution can influence the health of our gut bacteria we

31

first have to examine the make up of air pollution. Air pollution is a mixture

of a number of substances like carbon dioxide, carbon monoxide, nitric

oxide, and sulfur dioxide, ozone, benzene, polycyclic aromatic, and

biological components which include microbial particles,

lipopolysaccharide, and spores.

These pollutants reach our gut bacteria through two main pathways.

Firstly, they can be inhaled into your lungs, where they are quickly cleared

from our lungs to our gut by mucosal pathways.82 Secondly, these

airborne pollutants can contaminate our food and drink, and use them as

vehicles to reach our gut.83

As an extreme example, cigarette smoking is something ‘airborne’ that is

well known to alter your gut bacteria and increase your susceptibility of

developing irritable bowl disease by alerting your gut and gut bacteria.84

We are now finding associations between cities and communities that

have high airborne pollution and incidence of diabetes,85,86 as well as

associations between air pollution levels and blood pressure, inflammation

and other metabolic disorders.87

Recent animal research suggests that ingested pollutants are able to

influence gut bacteria richness88 and gut permeability89.

In human experiments, gut bacteria were also shown to transform a type

of pollutant called polycyclic aromatic hydrocarbons into compounds

that act like the female hormone estrogen in the body, showing that

pollution can even alter your hormonal profiles.90

32

Polycyclic aromatic hydrocarbons are a type of air pollution created

through combustion. They are commonly found in vehicle exhaust (traffic

pollution) and through the combustion of oils and other materials through

cooking (quick tip – always make sure your kitchen is well ventilated while

cooking).91

The bottom line is your daily exposure to airborne pollution is another way

that your gut bacteria are attacked and influenced in a way that is often

completely out of your control.

While you can take steps to reduce the pollution in your home (change

your air filters regularly, monitor your CO2 levels and have house plants),

there is little you can do to change the pollution in your outside

environment. This is another reason why supporting the health of your gut

bacteria through your diet is important to your overall health.

33

Mending a broken gut

It is now obvious that an unhealthy gut contributes to obesity, and

my theory is that it also contributes to the large variability in how much

weight people are capable of gaining and losing, as people with more

richness in their gut bacteria have a better resilience against weight gain.

We also know that our gut bacteria can be altered by many

environmental factors, including antibiotics and pollution. Thankfully they

can also be influenced by the food you choose to eat.92

Quite simply, our gut bacteria are constantly under attack. Attacked by

the antibiotics in our toothpaste and hand sanitizers, attacked by the

foods we eat, and attacked by the pollution in the air we breathe.

Luckily we have the ability to mend a broken gut by doing our best to

avoid overexposure to antibiotics whenever possible, lowering our

exposure to air pollution and by altering our foods choices to include

foods that are able to protect our gut bacteria from these attacks.

We can protect ourselves from negative health effects of endotoxins by

eating in a way that lowers our endotoxin levels, and that prevents the rise

in endotoxin levels that is typically associated with overeating.

34

By following some simple and straightforward guidelines we can not only

attempt to improve the richness of our gut bacteria, but also take steps to

protect our bodies from the Endotoxins that we are being exposed to.

In a recent scientific study published in Nature, researchers looked at the

gut bacteria of 123 non-obese and 169 obese individuals. Many of the

obese people had lower bacterial richness, insulin resistance, and

elevated markers of inflammation compared to the non-obese people,

and they were also prone to more weight gain.

When the obese individuals with low gut bacteria richness reduced their

calorie intake for 6 weeks, the researchers observed a dramatic

improvement in their gut bacteria richness, and this improvement

remained even after these people went back to eating a normal

‘maintenance’ amount of calories. They also saw improvements in insulin

sensitivity and markers of inflammation.93

The diet these subjects followed was not extreme by any means. It was

slightly higher in protein than average (roughly 120 grams per day), with

slightly lower than average fat intake (under 25% of total calories) and an

average carbohydrate intake. Truly a diet that could be endorsed by

most weight loss experts and easily maintained by most people.

This research outlines the first step in mending a broken gut – a simple

calorie reduced diet with moderate amounts of protein – aiming for

roughly 100 to 120 grams of protein per day with total fat intake under 25%

of total calories per day.

35

However, while a higher-protein, moderate fat, calorie-restricted diet can

improve gut bacteria richness, it is only a partial improvement. Since we

now know that food choices can have a dramatic effect on your gut

bacteria, this opens the door to the suggestion that calorie restriction plus

altered diet choices could result in further improvements.

The evidence has also shown that the health of your gut bacteria can be

influenced by exposure to antibiotic residues and antibiotic resistant

bacteria, so whenever possible choose antibiotic free foods, and an

antibiotic free lifestyle. Unless prescribed by your health care practitioner,

avoid antibiotic toothpaste, mouthwash, hand sanitizers, body soaps and

cosmetics (Look for the names ‘Triclosan’ or ‘Triclocarbon’). Whenever

possible choose antibiotic-free foods.

Next, we need to address Endotoxins. Specifically the toxin

Lipopolysaccharide (or LPS) that is produced by the ‘bad’ bacteria in your

gut, and that is associated with a whole host of diseases.

We may never be able to completely fix our gut bacteria, and to be

honest with you, I don’t think we know what an ideal gut bacteria richness

even looks like (We’re still years away from ‘mapping’ our ideal gut).

However, we do know that with the right food choices, Endotoxins can be

prevented from entering our bodies, even after we’ve consumed a high

calorie meal.

36

Reducing Endotoxins

Endotoxins are toxins produced by your gut bacteria. There will

always be some amount of endotoxins in your gut; however, the key to

staying healthy is keeping those toxins in your gut and not letting them

leak into your body. While fixing our gut bacteria richness is a long-term

project, combating endotoxins is something you can do right now.

At its core, endotoxemia is when the endotoxins like LPS from your gut find

their way into your blood stream, and is associated with chronic low-

grade inflammation.

Chronic, low-grade inflammation has long been recognized as a feature

of the ‘metabolic syndrome’ - a cluster of dysfunctions that tends to

precede full-blown diabetes and that also increases the risk of heart

disease, stroke, certain cancers, and even dementia—the top killers of the

developed world.94,95,96 It has also been shown to precede weight gain –

meaning people who have difficulty keeping their weight down are often

the same people who suffer from increased levels of chronic low-grade

inflammation.97,98

Interestingly, some antibiotics actually increase the release of endotoxins

into your body99, creating an interesting link between anti-biotic use,

endotoxins and weight gain.

37

For these reasons easy ways to reduce our endotoxin load are also part of

the approach to mending a broken gut.

Many studies show that people who follow a high-calorie and high-fat

diet also typically have high levels of endotoxins in their blood103. In other

words, the typical Western diet that most Americans eat is the prime

culprit in increasing levels of endotoxins levels and inflammation100,

whereas a healthy diet has been found to decrease the amount of

endotoxin activity.

Basically, the higher the calorie intake, the higher the risk of endotoxins

making their way into your blood stream. And, it’s not just your endotoxin

levels, inflammation is also tied to calorie intake.

The more you eat, the more risk you have of increasing inflammation and

endotoxin levels (The two tend to go hand-in-hand)101. And if you

remember from the first chapter the combination of endotoxemia and

inflammation can lead to insulin resistance and weight gain.102

There’s just no way around this, despite how we try to glorify big meals,

and times of overeating, the fact is, overeating is simply not good for you.

Even a single meal can raise endotoxin levels, especially when that meal

is high in sugars and fats.103

However there is huge caveat to this statement. It seems as though the

foods you choose to eat matter. Refined sugars and fats drive endotoxins

into your body, while fruits and vegetable seem to contain natural

protective mechanisms that help prevent endotoxins from entering our

bodies.

38

There is an abundance of research on the potent effects of a class of

nutrients called ‘polyphenols’ – special health promoting chemicals found

predominantly in fruits, vegetables, coffee, tea, chocolate and wine, and

their ability to reduce endotoxin load, even when combined with a high

fat, high sugar meal104.

Research on flavonoids and other polyphenols, their antioxidant

properties, and their effects in disease prevention is young by scientific

standards, as the research only truly began after 1995. Current evidence

strongly supports a contribution of polyphenols to the prevention of

cardiovascular diseases, cancers, and osteoporosis and suggests a role in

the prevention of neurodegenerative diseases and diabetes mellitus.105

Polyphenols tend to be very poorly absorbed and need to be altered in

order to enter your body. Many of these alterations occur in your gut

where healthy gut bacteria act on polyphenols from your food, creating

new compounds that can enter your blood stream and cause a whole

host of beneficial effects106.

Regardless of how polyphenols work, the fact remains that polyphenol

foods are effective at preventing fats and sugars from driving endotoxins

into your body. A perfect example of this comes from Orange Juice.

In a recently conducted study, a group of healthy people were divided

into three different groups. Each group received a typical fast-food high-

fat breakfast containing roughly 900 Calories. However, each group had

a different drink with their meal.

39

Group 1: Drank Water

Group 2: Drank a sugar and water drink

Group 3: Drank orange juice that contained the same amount of sugar as

the sugar and water drink.

The ingestion of the high calorie breakfast with either the sugar drink or the

water quickly induced oxidative stress and inflammation, as well as

increased endotoxemia.

On the other hand, the consumption of orange juice plus the high-fat

meal prevented an increase in endotoxin load and prevented an

increase in inflammation.107

Even though people typically think of orange juice and other fruit juices as

being ‘loaded with sugar’, and that water would have been the far

healthier option, the truth is there are compounds within fruit juices that

prevent the development of endotoxemia, even after a 900 Calorie fast-

food style breakfast.

Obviously, the endotoxin-lowering effect of orange juice most likely did

not come from the sugars, but rather the naturally occurring polyphenols

and even fiber that was ingested with the sugar.108 Whatever the

mechanism, we now know that a simple dose of flavanoids can prevent a

rise in endotoxemia and benefit your overall health.

Tea, chocolate and wine are possibly the most researched out of all the

high-polyphenol foods, however there are many different foods that

40

contain polyphenols and flavanoids. Basically, any fruit or vegetable

considered a ‘super food’ usually is also high in many different types of

polyphenols.109 As an example, a wild blueberry drink (notably high in

polyphenols called Anthocyanins) was able to significantly increase

healthy bacteria (Lactobacillus) in humans.110

Polyphenols can even protect from the downstream negative effects of

endotoxins. When people were fed a high dose of sugar for 6 straight

days with or without grape polyphenols, the grape polyphenols were able

to prevent a negative change in insulin sensitivity, whereas the 6 day of

eating high sugar without the polyphenols caused a 19% decrease in

fasting insulin sensitivity111.

Not only do polyphenols increase counts of beneficial bacteria, protect

against endotoxins and their negatie affects, they also inhibit growth of

potentially pathogenic bacteria. Catechin, a polyphenol found in tea,

chocolate, apples, and blackberries, has been shown to significantly

inhibit the growth of a type of bad bacteria called Clostridium

histolyticum.

Other polyphenol compounds contained in various berries have also

been studied, showing antimicrobial effects on bad bacteria like

Staphylococcus and Salmonella.112

Interestingly in a 24 year long study that followed people from1986 to 2010

it was found that the intake of fruits and vegetables that were high in

polyphenolic compounds like berries, apples and pear was inversely

associated with weight gain.

41

This means people who reported eating more of these types of foods

gained less weight than those who did not. These findings took into

account differences in lifestyle factors like exercise, calorie intake, and

whether or not the people in the study were smokers.113

By now you understand that eating a responsible amount of calories

combined with a slightly elevated protein intake (100-120 grams per day)

and slightly reduced fat intake (under 25% of total calories) while

choosing foods that are rich in as many types of polyphenols as possible,

will help you maintain the richness of your gut bacteria, while decreasing

the risk of endotoxins entering your body. Whenever you are having a big

meal full of carbohydrates and fats, make sure to include fruits and

vegetables with your meal to prevent the rise in endotoxins and

inflammation typically associated with large meals.

It is not only fruits and vegetables that contain polyphenols. Common

flavoring agents such as oregano, cloves, celery seeds, rosemary, sage,

thyme, peppermint and spearmint are also high in polyphenols114.

All of these steps will keep you on the right track of improved health and

maintaining a healthy, leaner you.

You will of course want to exclude any polyphenol-rich foods that you are

sensitive to (a lot of people have difficulty with Tea and Red wines), but

otherwise include as many as you’d like!

Next, I’d like to discuss practical ways to combat the chronic low-grade

inflammation that is associated with endotoxemia.

42

Combating Inflammation

An unhealthy gut is associated with endotoxemia and endotoxemia

is associated with chronic low-grade inflammation. This type of

inflammation (especially in combination with endotoxemia) is associated

with many disease states including: Rheumatoid arthritis, hypertension,

atherosclerosis, fatty liver and asthma as well as insulin resistance,

cardiovascular disease and diabetes, and even the aging process

itself.115116

For this reason, chronic inflammation is believed to be one of the major

links between gut bacteria, obesity and many of the life threatening

diseases that are associated with being overweight.117

The combination of endotoxemia and chronic inflammation is widely

observed in obesity and overeating.118 In people who are obese we

commonly see many elevated markers of inflammation including:

Interleukin-6, Tumor Necrosis Factor Alpha, C-reactive protein, Insulin,

blood glucose, Leptin and Interleukin-18.119 Luckily, there is an easy to

implement a strategy to help deal with chronic-low grade inflammation.

Short-term fasting, and the calorie restriction and weight loss it causes, is

able to greatly reduce markers of chronic inflammation.120,121,122 Combine

this with the health promoting effects of fasting123, its ability to lower

endotoxin levels124, and the fact that recently short-term fasting has shown

43

to increase gut bacteria richness in animal models60, and we have good

evidence to suggest a weekly, 20-24 hour fast as part of our overall

strategy.

Eating less and exercising also have direct effects on reducing

inflammation, so by doing all three you create a synergistic ‘attack’ on

inflammation.

Keeping inflammation under control is important for a number of reasons,

including overall health, your ability to lose weight and even your ability to

build muscle. Even a small increase in chronic inflammation can increase

the risk of muscle strength loss and cause a decrease in your ability to

build muscle. In fact, endotoxemia and chronic inflammation have been

implicated as part of the cause of the muscle loss that occurs with aging

(sarcopenia).

Our plan to help mend a broken gut and to lower endotoxins and

inflammation now includes a slightly lower calorie intake with roughly 100

to 120 grams of protein per day and a fat intake of under 25% of total

calories. This approach is to be combined with a diet full of fruits and

vegetables and a 24 hour fast once or twice per week.

Finally I’d like to touch on something called Resistant Starches.

44

Resistant Starches

Most of the carbohydrates in your diet are either simple sugars or

starches. Starches are long chains of glucose that are found in grains,

potatoes and various other foods. Interestingly, not all of the starch we eat

gets digested. Sometimes a small portion of it passes through the digestive

tract unchanged. In other words, it is resistant to digestion.

This type of starch is called resistant starch. Many studies in humans show

that resistant starch can have powerful health benefits, such as improved

insulin sensitivity125, lower blood sugar levels, reduced appetite and various

benefits for digestion. Currently it’s estimated that Americans eat between

3 and 8 grams of resistant starches per day126, while the recommendation

is to consume between 20 and 40 grams per day127.

Resistant starches are similar to soluble fibers – they are able to travel

through the stomach and small intestine undigested, allowing them to

reach the colon where it feeds your gut bacteria.128

Resistant starch is considered to be a form dietary fiber, as it is not

degraded in the small intestine and thus reaches the large intestine intact,

where it is partially fermented by your gut bacteria.

Several health promoting properties have been described for resistant

45

starch. First, it acts as a dietary fiber and it thus has a positive effect on

the health of your gut bacteria. Resistant starch is completely degraded

and fermented by the bacteria in the large intestine. These bacteria

produce relatively high amounts of butyrate from resistant starch, and

butyrate may prevent the formation of intestinal cancers.

There is direct evidence that changing the amount and/or type of

carbohydrate over periods of up to four weeks has a profound and rapid

influence on the composition of the gut bacteria and its metabolic

products in adult human volunteers129,130

Secondly, Resistant starch can also easily be used by diabetic patients as

it has no effect on the blood glucose level, and has a beneficial effect on

insulin sensitivity and fatty acid oxidation.131 Interestingly, typical

commercially purchased bread that has been frozen, thawed then

toasted will cause a lower increase in blood glucose levels than simple

bread that was not frozen then toasted132.

Thirdly, resistant starches supply less calories to your body then traditional

starches. For many years it was believed that starch was completely

digested and absorbed in the small intestine. But studies published in the

1980s, based on hydrogen breath testing, showed that oats, wheat,

potatoes, corn, and beans contained 10 to 20% malabsorbed,

fermentable material. This means that 10 to 20% of the calorie content of

retrograded starches do not enter your body.

Finally, while it does not seem likely that simply adding some resistant

starch to your diet will completely ‘fix your gut’, it does seem to have the

ability to improve it. However, this isn’t the reason only reason for

46

recommending increasing your resistant starch intake; resistant starches

can also improve your health by preventing endotoxins and other toxic

compounds from entering your body.133 For these reasons 20-40 grams of

resistant starches per day are part of our overall gut mending, endotoxin

fighting strategy.

Adding resistant starches to your diet involves eating foods that have

been through ‘Retrogradation’. Retrogradation is a process that turns

regular starch into resistance starch through the process of cooking and

cooling. Bread, cornflakes and cooked-and-chilled potatoes and rice are

all examples of retrograded starches.

When you cook, then cool starch containing foods like you would in

making potato salad, you cause an increase in retrogradation and thus

the resistant starch content of the potatoes. Five degrees Celsius (roughly

the temperature of your average refrigerator) seems to be about the best

temperature for retrogradation of potato starch.

Choosing foods naturally high in resistant starches like pumpernickel

bread, humus, toasted bread and beans, as well as eating more chilled

dishes like potato salad will help you reach 20-40 grams of resistant

starches per day.

As a caveat I recommend increasing your intake of resistant starches

slowly. Just like fiber, suddenly increasing your intake of resistant starches

can lead to Gastrointestinal upset. Start small and increase slowly,

especially since you will already be increasing your fiber intake by

increasing your intake of berries and other fruits.

47

Conclusions

For years I have been a staunch advocate of ‘calories in, calories

out’ – that your ability to lose weight was determined solely by the

amount of calories you eat in any given day, and the amount of calories

you expend in any given day.

For this reason I had a very hard time giving people typical ‘healthy

eating’ recommendations. Believe it or not it was difficult for me to explain

to people that while I knew weight loss was a mathematical formula of

calories in and calories out, I also knew that eating healthy was somehow

beneficial.

I know it sounds silly, that a well known nutrition author had a hard time

explaining why people should eat healthy, but the truth is now I finally

have that reason – A scientifically valid reason to suggest a healthy eating

regimen COMBINED with a responsible calorie intake as the preferred

method of weight loss.

After all, you will absolutely lose weight by eating less, but you might be

able to lose more weight in a shorter period of time by eating less

COMBINED with eating healthy foods that support healthy bacteria, and

that help prevent endotoxins from entering your body.

48

It’s been shown that as little as 4 weeks of eating a typical western-style

diet of high fat, high sodium, low fiber can increase endotoxemia by 71%,

while a more prudent diet lower in fat, higher in fiber and less typical of a

western diet is able to lower endotoxemia by more that 30%.134 If

endotoxins matter, then so do your food choices.

In fact, after 4 years of research I can tell you that I believe I have

answered both of my questions.

YES, your gut bacteria can influence your tendency to gain weight, and

YES your gut bacteria can influence your ability to lose weight.

Of course, there are dozens of books now available on Gut Bacteria, but I

feel many of them to be far too complicated, and usually have complex

and often contradictory views on the best way to mend a broken gut. I

was disappointed to find that far too often these diets promise that by

simply adding some fermented foods to your diet, or by taking probiotic

supplements you can create a perfectly healthy gut, even though the

meaning of ‘a perfectly healthy gut’ is still the topic of intense scientific

debate. More importantly, almost all of these books fail to address the

more pressing issue of gut-derived endotoxins.

There is no such thing as permanent weight loss, nor is there such thing as

a permanently healthy gut. As I’ve mentioned throughout this book, your

gut bacteria are constantly under attack. You can eat the world’s most

perfect, gut-friendly diet but you will never be able to completely avoid

air pollution or exposure to antibiotics or even the occasional period of

overeating.

49

These attacks lead to a rise in endotoxins entering you body, and while I

agree that our long-term goal should be to create and support a healthy

gut, our immediate need is to reduce the amount of endotoxins that are

entering our bodies.

Luckily, the research is clear that eating in a way that allows you to lose

weight and that supports the health of your gut bacteria, is also vital in

combating endotoxin levels.

This research combines to create a very straightforward, very doable

approach to weight loss and gut health. A simple calorie reduced diet

with moderate amounts of protein – aiming for roughly 100 to 120 grams

of protein per day and slightly reduced fat intake (under 25% of total

calories) is the first step. This one step alone has been shown to improve

gut bacteria richness and be an effective method of weight loss.

The second step is whenever possible choose antibiotic free foods, and

avoid anti-bacterial soaps, cleaners, toothpaste and mouthwash. The

evidence shows that the health of your gut bacteria can be influenced

by exposure to food that contains high amounts of antibiotic residues and

antibiotic resistant bacteria. Also, monitor the air quality of your house and

work place. Change your furnace filters and invest in an air purifier, do the

little things that help improve your health.

Next, fruits and vegetables contain both fiber and polyphenols that have

been shown to help combat the endotoxemia and the inflammation that

is associated with obesity and overeating. No matter the mechanism, we

know that the flavonoids and polyphenols from fruits and vegetables are

welcome additions to your diet. Your diet should include as much ‘color’

50

as possible; berries, dark vegetables and citrus fruits should be a part of

your daily diet.

Resistant starches are a special type of starch that avoids digestion in your

stomach and small intestine, and are thus able to feed your bacteria,

improve your bacterial richness, reduce your appetite and provide health

promoting by products to your body. Because of this it is easy to

recommend adding resistant starches like those found in cooked and

cooled potatoes and rice to your diet.

Finally, short-term fasting has been shown to be an excellent way to

reduce your overall calorie intake, promote fat loss, reduce inflammation

and improve many markers of health. Best of all, you don’t have to fast

every day. A simple weekly 20-24 hour fast should be enough to help in

the process of mending the damage from a broken gut.

To be clear, I’m not saying that simply increasing your protein intake and

lowering your fat intake will lead to weight loss. Nor am I saying that

increasing the amount of polyphenols you eat will make you impervious to

weight gain, or that all you have to do is fast once a week and you’ll look

like a movie star.

Rather, my findings are that the combination of a reduced calorie diet

with moderately high protein and under 25% fat, combined with a diet

that is high in polyphenol containing fruits and vegetables and resistant

starches, along with the occasionally 24 hour fast is a research backed

suggestion to help you reduce weight and improve the richness of your

gut bacteria.

51

I believe this is a method that almost anyone can do, that is in line with

most views of ‘healthy eating’ and that does not include eliminating

major food groups from your diet, or perpetually being on an

unsustainable, unenjoyable diet program.

You can still enjoy the occasional period of overeating, just be sure to up

your polyphenol intake when you do. And remember, some of the most

enjoyable decadent foods like chocolate, coffee and wine are high in

polyphenols.

In conclusion, to maximize the health of your gut bacteria, and to avoid

the negative health-harming effects of endotoxemia, avoid overexposure

to antibiotics and air pollution, eat a lower calorie diet focused on fruits

and vegetables, that includes a moderately high protein intake with a fat

intake of under 25% of total calories and 20-40 grams of resistant starches

per day.

52

Additional Questions:

Q: If I’m concerned about endotoxin levels, am I allowed to drink

alcohol?

It is absolutely true that acute intake increases endotoxin levels135,

however, many beers contain polyphenols, but the amounts can vary

from beer to beer, and even the same beer from different locations. As an

example Guinness Draught has 247 mg polyphenols per liter whereas

Guinness Foreign Stout has 446 mg per liter136. So your choice of drink

matters, even what you mix your alcohol with maters.

Animal research has found the polyphenols found in lemon and lime

reduce endotoxin levels137.

To answer your question acute alcohol or high levels of alcohol intake do

increase endotoxin levels, however moderate levels of alcohol intake

especially dark beers, redwine or drinks that include citrus, may in fact

help control endotoxin levels.

Q: I’d like to add more resistant starches to my diet, what are some top

food choices?

53

Generally foods that contain 4 grams of resistant starches per every 100

grams of food are said to be high in resistant starches. Toasted bread has

4 grams per every 100 grams, whereas the equivalent amount of bread

will have only 1.5 grams. Pumpernickel bread (even untoasted) can have

as much as 4.5 grams per 100 grams of bread. Raw bananas can be as

high as 4 grams per every 100 grams, and many beans and lentils can

also have around 4 grams per every 100 grams (hummus can be as high

as 4 grams per 100 grams as well). Heating then cooling foods like

potatoes and rice can more than double their content of resistant

starches reaching that 4 gram per every 100 grams mark.

Q: What about taking resistant starch supplements?

Since foods considered high in resistant starches have roughly 4 grams per

100 grams of food, these resistant starches are always found with other

complex carbohydrates and fibers. For this reason I’d like to stick with

resistant starches containing foods instead of supplements. If you do

choose to supplement please only take resistant starches with a full meal.

Q: What are some top Polyphenol containing foods I can add to my diet?

Your best choices would be dark chocolate, blueberries, olives (green

and black), black currants, plums, cherries, blackberries, cloves, hazelnuts,

pecans, orange juice, red wine, and dark coffee. Basically look for natural

foods that are rich in color.

Q: What about Exercise?

54

Strenuous and exhausting exercise like marathons have consistently been

shown to increase endotoxemia138,139,140. However I’m curious if altering

your diet to include a high amount of polyphenols before or even during

exercise may help. The research in this area is lacking so until more

research becomes available I suggest using exhaustive exercise in

moderation.

Q: What about Fermented Foods?

Fermented foods like Kefir, Kumboucha, sauerkraut and pickles can be

used to help promote a healthy, rich and diverse gut bacteria, however I

view this as part of the long term strategy, secondary to the immediate

concern of address endotoxin levels.

Q: Is there really evidence from human research that antibiotics make us

fat?

A: yes a 1954 study conducted on US Navy recruits found that men who

were given a dose of antibiotics every morning for seven weeks gained

more weight than the men who didn’t receive antibiotics.

A similar study was conducted in the 1950s on institutionalized children.

Children were given antibiotics twice daily for periods of up to three years

at the Florida Farm Colony. The average yearly gain in weight for the

supplemented group was 6.5 lb while the control group averaged 1.9 lb in

yearly weight gain.

Q: You’ve mentioned carbohydrates and fats, but not really protein, can

having a high protein diet increase endotoxin levels?

55

I have not found any convincing evidence that protein by itself can

increase risk of endotoxemia. There is evidence to suggest that a diet high

in animal protein can have a negative affect on your gut bacteria

richness, however I’m not sure if having a diet that is ALSO high in fruits

and vegetables would cancel out this effect. The bottom line is I have

found no clear evidence that a high protein diet increases the risk of

endotoxins entering your blood.

Q: Should I be concerned about food additives?

The short answer is yes. Artificial sweeteners, benzene derivatives and food

dyes are all known to affect the metabolism of your gut bacteria, and

your gut bacteria are known to be able to alter several of these

substances141. Limit intake when reasonable, and perhaps consider

including some high polyphenol foods with meals that may be high in

these additives.

Q: It seems like you are promoting a plant-based diet and against a

Paleo-style diet, is this correct?

Not really, while I am definitely promoting a plant-based diet, these

findings also fall in line with traditional Paleo eating. From my

understanding ‘Paleo’ is a diet based on the combination of animal fats

with fruits and vegetables. Essentially, if Veganism is a plant-based diet

devoid of any animal products, Paleoism is a plant-based diet that

includes animal products.

56

References

1 Scientific American Article by Rachel Feltmen on December 14, 2013 2 Candela, M. et al. Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: adhesion properties, competition against enteropathogens and modulation of IL-8 production. Int. J. Food Microbiol. 125, 286–292 (2008) 3 Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011). 4 Devillard, E., McIntosh, F. M., Duncan, S. H. & Wallace, R. J. Metabolism of linoleic acid by human gut bacteria: different routes for biosynthesis of conjugated linoleic acid. J. Bacteriol. 189, 2566–2570 (2007) 5 Bäckhed, F.et al.The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004) 6 Olszak, T. et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336, 489–493 (2012) 7Patel PN, Shah RY, Ferguson JF, Reilly MP. Human experimental endotoxemia in modeling the pathophysiology, genomics, and therapeutics of innate immunity in complex cardiometabolic diseases. Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):525-34 8Boroni Moreira AP, de Cássia Gonçalves Alfenas R. The influence of endotoxemia on the molecular mechanisms of insulin resistance. Nutr Hosp. 2012 Mar-Apr;27(2):382-90. 9Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, Louche K, Bourlier V, Roussel B, Gui P, Grober J, Štich V, Rossmeislová L, Zakaroff-Girard A, Bouloumié A, Viguerie N, Moro C, Tavernier G, Langin D. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014 May 22;7(4):1116-29. 10 National Institutes of Health, U.S. Department of Health and Human Services. Opportunities and Challenges in Digestive Diseases Research: Recommendations of the National Commission on Digestive Diseases. Bethesda, MD: National Institutes of Health; 2009. NIH Publication 08–6514. 11 Forsythe P, Kunze WA, Bienenstock J. On communication between gut microbes and the brain. Curr Opin Gastroenterol. 2012;28:557-562.

57

12Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. Journal of Clinical Endocrinology and Metabolism. 2004; 89:2548–2556. 13 Carvalho BM, Saad MJ. Influence of gut microbiota on subclinical inflammation and insulin resistance. Mediators Inflamm. 2013:986734. 14 Parnell JA, Reimer RA Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 2009;89:1751–9. 15 Patrice D. Cani, Melania Osto, Lucie Geurts, and Amandine Everard Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012 July 1; 3(4): 279–288. 16 Murphy EF, Cotter PD, Hogan A, et al. Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut. 2013;62:220-226. 17 Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010). 18 The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012). 19 Jalanka-Tuovinen J, Salonen A, Nikkilä J, et al. Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms. PLoS One. 2011;6:e23035 20 Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012 Sep 13;489(7415):220-30 21 Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012) 22 De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010) 23 Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010) 24 Manichanh, C.et al.Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55, 205–211 (2006) 25 Lepage, P.et al.Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141, 227–236 (2011) 26 Logan AC, Rao, AV, Irani D. Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value. Medical hypotheses (2003) 60(6); 915-923

58

27 Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 488, 178–184 (2012) 28 Le Chatelier E, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013 Aug 29;500(7464):541-6. 29 Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4615-4622 30 Wang Y, Kasper LH.The role of microbiome in central nervous system disorders. Brain Behav Immun. 2013 Dec 25. 31 Vaarala O, Atkinson MA, Neu J. The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008;57:2555-2562 32 Hara N, Alkanani AK, Ir D, et al. The role of the intestinal microbiota in type 1 diabetes. Clin Immunol. 2013;146:112-119 33 Dicksved, J. et al. Molecular analysis of the gut microbiota of identical twins with Crohn’s disease. ISME J. 2, 716–727 (2008) 34 Lupton, J. R. Microbial degradation products influence colon cancer risk: the butyrate controversy. J. Nutr. 134, 479–482 (2004) 35 Xiao S, Zhao L.Gut microbiota-based translational biomarkers to prevent metabolic syndrome via nutritional modulation. FEMS Microbiol Ecol. 2013 Nov 12 36Kelly CJ, Colgan SP, Frank DN. Of microbes and meals: the health consequences of dietary endotoxemia. Nutr Clin Pract. 2012 Apr;27(2):215-25. 37 Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575-1584 38 Scher JU, Sczesnak A, Longman RS, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013;2:e01202 39Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008;29(1):117-24. 40 Opal SM. Endotoxins and other sepsis triggers Contrib Nephrol. 2010;167:14-24 41 Cani, PD; Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D et al. (2007). "Metabolic endotoxemia initiates obesity and insulin resistance.". Diabetes 56: 1761–1772 42 Boutagy NE, McMillan RP, Frisard MI, Hulver MW. Metabolic endotoxemia with obesity: Is it real and is it relevant? Biochimie. 2016 May;124:11-20.

59

43Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care 2010;33:991–99744Amar J, Burcelin R, Ruidavets JB, Cani PD, Fauvel J, Alessi MC, Chamontin B, Ferriéres J.Energy intake is associated with endotoxemia in apparently healthy men. American Journal of Clinical Nutrition 87(5):1219-23 45 Luı´sa Neves A, Coelho J, Couto L, Leite-Moreira A and Roncon-Albuquerque Jr R. Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. Journal of Molecular Endocrinology (2013) 51, R51–R64 46 Kallus SJ, Brandt LJ. The intestinal microbiota and obesity. J Clin Gastroenterol. 2012;46:16-24 47 Ramachanrappa S and Farooqi I.S. Genetics approaches to understanding human obesity. Journal of Clinical investigation. 2011 121:2080-2086 48 Tremblay A, Despres JP, Therault G, Fournier G, bouchard C. Overfeeding and energy expenditure in humans. Am J Clin Nutr 1993:56:857-62 49 Bouchard C, Tremblay A, Després JP, Nadeau A, Lupien PJ, Thériault G, Dussault J, Moorjani S, Pinault S, Fournier G.The response to long-term overfeeding in identical twins. N Engl J Med. 1990 May 24;322(21):1477-82 50 Pontzer H, Raichlen DA, Wood BM, Mabulla AZ, Racette SB, Marlowe FW.Hunter-gatherer energetics and human obesity. PLoS One. 2012;7(7):e40503. 51 Prentice AM, Black AE, Coward WA, Cole TJ. Energy expenditure in overweight and obese adults in affluent societies: an analysis of 319 doubly-labelled water measurements.Eur J Clin Nutr. 1996 Feb;50(2):93-7 52 Swinburn BA, Sacks G, Lo SK, Westerterp KR, Rush EC, Rosenbaum M, Luke A, Schoeller DA, DeLany JP, Butte NF, Ravussin E.Estimating the changes in energy flux that characterize the rise in obesity prevalence.Am J Clin Nutr. 2009 Jun;89(6):1723-8 53 Bäckhed, F.et al.The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004) 54 Devillard, E., McIntosh, F. M., Duncan, S. H. & Wallace, R. J. Metabolism of linoleic acid by human gut bacteria: different routes for biosynthesis of conjugated linoleic acid. J. Bacteriol. 189, 2566–2570 (2007) 55 Rossi M, Amaretti A, Raimondi S.Folate production by probiotic bacteria.Nutrients. 2011 Jan;3(1):118-34. 56 Metges CC et al. Availability of intestinal microbial lysine for whole body lysine homeostasis in human subjects. American Journal of Physiology, 1999, 277:E597–E607.

60

57 Metges CC et al. Incorporation of urea and ammonia nitrogen into ileal and fecal microbial proteins and plasma free amino acids in normal men and ileostomates. American Journal of Clinical Nutrition, 1999, 70:1046–1058. 58 Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006). 59 Le Chatelier E, et al. Richness of human gut microbiome correlates with metabolic markers.Nature. 2013 Aug 29;500(7464):541-6. 60 Kohl, KD, Amaya J, Passement A, Dearing MD and McCue MD. Unique and shared responses of the gut microbiota to prolonged fasting: a comparative study across five classes of vertebrate hosts. FEMS Microbiol Ecol 90 (2014) 883–894 61 Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006) 62 Dethlefsen, L., S. Huse, M. L. Sogin, and D. A. Relman. 2008. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 6:e280. 63 Jakobsson HE et al Short-term antibiotic treatement ha differing long-term impacts on the human throat and gut microbiome. PLoS ONE 5s, e9836 (2010). 64 Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 1 56-66 (2007) 65 Ajslev, T. A., Andersen, C. S., Gamborg, M., Sorensen, T. I. & Jess, T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int. J. Obes. 35, 522–529 (2011) 66 Office-related antibiotic prescribing for persons aged ≤14 years -- United States, 1993-1994 to 2007-2008. MMWR Morb Mortal Wkly Rep 2011;60:1153-1156 67Hicks LA, Bartoces MG, Roberts RM, Suda KJ, Hunkler RJ, Taylor TH Jr, Schrag SJ. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis. 2015 May 1;60(9):1308-16. 68 Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A (2011) 108(Suppl 1):4554–61. 69 Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ. Infant antibiotic exposures and early-life body mass.Int J Obes (Lond). 2013 Jan;37(1):16-23. 70 Thuny F, Richet H, Casalta JP, Angelakis E, Habib G, Raoult D. Vancomycin treatment of infective endocarditis is linked with recently acquired obesity. PLoS One (2010) 5(2):e9074.10.1371/journal.pone.0009074 71 Duran GM, Marshall DL. Ready-to-eat shrimp as an international vehicle of antibiotic-resistant bacteria. J Food Prot. 2005 Nov;68(11):2395-401.

61

72 Campos J, Mourão J, Pestana N, Peixe L, Novais C, Antunes P. Microbiological quality of ready-to-eat salads: an underestimated vehicle of bacteria and clinically relevant antibiotic resistance genes.Int J Food Microbiol. 2013 Sep 16;166(3):464-70. 73 Brown JC, Jiang X. Prevalence of antibiotic-resistant bacteria in herbal products. Food Prot. 2008 Jul;71(7):1486-90. 74 http://www.takepart.com/article/2013/04/06/antibiotic-use-organic-apples-pears 75 http://www.tufts.edu/med/apua/about_issue/agents.shtml 76 FSNET. 2000. Survey of U.S. Stores reveals widespread availability of soaps containing potentially harmful antibacterial agents. Centre for Safe Food, University of Guelph. September 10. 77 Halden RU, Paull DH. Co-occurrence of triclocarban and triclosan in U.S. water resources.Environ Sci Technol. 2005 Mar 15;39(6):1420-6. 78 Möller W, Häussinger K, Winkler-Heil R, Stahlhofen W, Meyer T, Hofmann W, Heyder J. Mucociliary and long-term particle clearance in the airways of healthy nonsmoker subjects. J Appl Physiol (1985) 2004;97:2200–6. 79 Kaplan GG, Hubbard J, Korzenik J, Sands BE, Panaccione R, Ghosh S, Wheeler AJ, Villeneuve PJ. The inflammatory bowel diseases and ambient air pollution: a novel association. Am J Gastroenterol. 2010 Nov; 105(11):2412-9. 80 Ananthakrishnan AN, McGinley EL, Binion DG, Saeian K. Ambient air pollution correlates with hospitalizations for inflammatory bowel disease: an ecologic analysis. Inflamm Bowel Dis. 2011 May; 17(5):1138-45. 81 Kaplan GG, Szyszkowicz M, Fichna J, Rowe BH, Porada E, Vincent R, Madsen K, Ghosh S, Storr M. Non-specific abdominal pain and air pollution: a novel association. PLoS One. 2012; 7(10):e47669. 82 Möller W, Häussinger K, Winkler-Heil R, Stahlhofen W, Meyer T, Hofmann W, Heyder J. Mucociliary and long-term particle clearance in the airways of healthy nonsmoker subjects.. J Appl Physiol (1985). 2004 Dec; 97(6):2200-6. 83 Beamish LA, Osornio-Vargas AR, Wine E. Air pollution: An environmental factor contributing to intestinal disease. J Crohns Colitis. 2011 Aug; 5(4):279-86. 84 Calkins BM.A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci. 1989 Dec; 34(12):1841-54. 85Chen H, Burnett RT, Kwong JC, Villeneuve PJ, Goldberg MS, Brook RD, van Donkelaar A, Jerrett M, Martin RV, Brook JR, Copes R. Risk of incident diabetes in relation to longterm exposure to fine particulate matter in Ontario, Canada. Environ Health Perspect. 2013 Jul;121(7):80410. 86Tang M, Chen K, Yang F, Liu W. Exposure to organochlorine pollutants and type 2

62

diabetes: a systematic review and metaanalysis. PLoS One. 2014 Oct 15;9(10):e85556. 87Chuang KJ, Yan YH, Chiu SY, Cheng TJ. Longterm air pollution exposure and risk factors for cardiovascular diseases among the elderly in Taiwan. Occup Environ Med. 2011 Jan;68(1):648. 88 Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, et al. (2001) Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 121: 580–591 89 Kish L, Hotte N, Kaplan GG, et al. Environmental Particulate Matter Induces Murine Intestinal Inflammatory Responses and Alters the Gut Microbiome. Bereswill S, ed. PLoS ONE. 2013;8(4):e62220. 90 Van de Wiele T, Vanhaecke L, Boeckaert C, Peru K, Headley J, Verstraete W, Siciliano S. Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites. Environ Health Perspect. 2005;113:6–10. 91 Byeong-Kyu Lee (2010). Sources, Distribution and Toxicity of Polyaromatic Hydrocarbons (PAHs) in Particulate Matter, Air Pollution, Vanda Villanyi (Ed.), InTech, DOI: 10.5772/10045. 92 Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD. Linking long-term dietary patterns with gut microbial enterotypes.Science. 2011 Oct 7;334(6052):105-8. 93 Cotillard A, et al. Dietary intervention impact on gut microbial gene richness. Nature 500, 585–588 (29 August 2013) 94 Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000;51:245-70. Review. 95 Ershler WB, Sun WH, Binkley N. The role of interleukin-6 in certain age-related diseases. Drugs Aging. 1994 Nov;5(5):358-65. Review. 96 Bharat B. Aggarwal, R.V. Vijayalekshmi, and Bokyung Sung. Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe. Clinical Cancer Research 2009; 15(2): 425-430. 97 Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002 Oct 15;106(16):2067-72. 98 Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM. Leptin regulates proinflammatory immune responses. Federation of American Societies for Experimental Biology Journal. 1998 Jan;12(1):57-65.

63

99Eng RH, Smith SM, Fan-Havard P, Ogbara T. Effect of antibiotics on endotoxin release from gram-negative bacteria. Diagn Microbiol Infect Dis. 1993 Mar-Apr;16(3):185-9. 100Patel C, Ghanim H, Ravishankar S, Sia CL, Viswanathan P, Mohanty P, Dandona P.Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metab. 2007 Nov;92(11):4476-9. 101Laugerette F, Alligier M, Bastard JP, Drai J, Chanséaume E, Lambert-Porcheron S, Laville M, Morio B, Vidal H, Michalski MC. Overfeeding increases postprandial endotoxemia in men: Inflammatory outcome may depend on LPS transporters LBP and sCD14. Mol Nutr Food Res. 2014 Jul;58(7):1513-8. 102Trøseid M, Nestvold TK, Rudi K, Thoresen H, Nielsen EW, Lappegård KT.Plasma lipopolysaccharide is closely associated with glycemic control and abdominal obesity: evidence from bariatric surgery. Diabetes Care. 2013 Nov;36(11):3627-32. 103Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 2009;32:2281–2287104Ghanim H, Sia CL, Korzeniewski K, et al. A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal. J Clin Endocrinol Metab 2011;96:1409–1414105Scalbert A, Manach C, Morand C, Rémésy C, Jiménez L. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr (in press).106Kaulmann A, Bohn T. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases-Promises, Perspectives, and Pitfalls. Oxid Med Cell Longev. 2016;2016:9346470. 107Ghanim H, Sia CL, Upadhyay M, Korzeniewski K, Viswanathan P, Abuaysheh S, Mohanty P, Dandona P. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression.Am J Clin Nutr. 2010 Apr;91(4):940-9. 108Clemente-Postigo M, Queipo-Ortuño MI, Boto-Ordoñez M, Coin-Aragüez L, Roca-Rodriguez MM, Delgado-Lista J, Cardona F, Andres-Lacueva C, Tinahones FJ. Effect of acute and chronic red wine consumption on lipopolysaccharide concentrations. Am J Clin Nutr. 2013 May;97(5):1053-61. 109Ford CT, Richardson S, McArdle F, Lotito SB, Crozier A, McArdle A, Jackson MJ. Identification of (poly)phenol treatments that modulate the release of pro-inflammatory cytokines by human lymphocytes. Br J Nutr. 2016 May 28;115(10):1699-710 110Vendrame S, Guglielmetti S, Riso P, Arioli S, Klimis-Zacas D, Porrini M. Six-week

64

consumption of a wild blueberry powder drink increases bifidobacteria in the human gut. J Agric Food Chem. 2011 Dec 28;59(24):12815-20. 111Hokayem M, Blond E, Vidal H, Lambert K, Meugnier E, Feillet- Coudray C, Coudray C, Pesenti S, Luyton C, Lambert-Porcheron S, Sauvinet V, Fedou C, Brun JF, Rieusset J, Bisbal C, Sultan A, Mercier J, Goudable J, Dupuy AM, Cristol JP, Laville M, Avignon A (2013) Grape polyphenols prevent fructose-induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients. Diabetes Care 36:1454–1461 112Puupponen-Pimiä R, Nohynek L, Hartmann-Schmidlin S, Kähkönen M, Heinonen M, Määttä-Riihinen K, Oksman-Caldentey KM.Berry phenolics selectively inhibit the growth of intestinal pathogens. J Appl Microbiol. 2005;98(4):991-1000. 113Bertoia ML, Mukamal KJ, Cahill LE, Hou T, Ludwig DS, Mozaffarian D, Willett WC, Hu FB, Rimm EB.Changes in Intake of Fruits and Vegetables and Weight Change in United States Men and Women Followed for Up to 24 Years: Analysis from Three Prospective Cohort Studies. PLoS Med. 2015 Sep 22;12(9):e1001878. 114J Pérez-Jiménez, V Neveu, F Vos and A Scalbert. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. European Journal of Clinical Nutrition (2010) 64, S112–S120 115 Senn JJ, Klover PJ, Nowak IA, and Moony RA. IL-6 Induces Cellular Insulin Resistance in Hepatocytes. Diabetes. 2002; 51(12):3391-9. 116Chung HY, Kim HJ, Kim JW, Yu BP. The inflammation hypothesis of aging: molecular modulation by calorie restriction. Annals of the New York Academy of Sciences. 2001; 928:327-35.117Boutagy NE, McMillan RP, Frisard MI, Hulver MW. Metabolic endotoxemia with obesity: Is it real and is it relevant? Biochimie. 2016 May;124:11-20. 118Patel C, Ghanim H, Ravishankar S, Sia CL, Viswanathan P, Mohanty P, Dandona P.Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metab. 2007 Nov;92(11):4476-9. 119Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002 Oct 15;106(16):2067-72.120Dandona P, Aljada A, Bandyopadhyay A.: Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 2004; 25: 4– 7121Fishebin L, Biological effects of Dietary Restriction. Springer-Verlag, New York.1991.

65

122Dixit VD. Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span. Journal of Leukocyte Biology. 2008: 84:882-892. 123 Pilon, B. Eat Stop Eat. 2013 124Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72. 125 Johnston KL, Thomas EL, Bell JD, Frost GS, Robertson MD. Resistant starch improves insulin sensitivity in metabolic syndrome. Diabet Med. 2010 Apr;27(4):391-7. 126Murphy MM et al. Resistant Starch Intakes in the United States J Am Diet Assoc. 2008;108:67-78 127Zhou J, Hegsted M, McCutcheon KL, Keenan MJ, Xi X, Raggio AM, Martin RJ. Peptide YY and proglucagon mRNA expression patterns and regulation in the gut. Obesity 2006;14:683-689. 128Englyst HN, Kingman SM, Hudson GJ, Cummings JH. Measurement of resistant starch in vitro and in vivo. Br J Nutr. 1996 May;75(5):749-55. 129 Brinkworth GD, Noakes M, Clifton PM, Bird AR. Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. British Journal of Nutrition 2009;101:1493–502. 130 Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME Journal 2011;5:220–30. 131Higgins JA, Higbee DR, Donahoo WT, Brown IL, Bell ML, Bessesen DH. Resistant starch consumption promotes lipid oxidation. Nutr Metab . 2004;1:8-18 132 P Burton and HJ Lightowler. The impact of freezing and toasting on the glycaemic response of white bread. European Journal of Clinical Nutrition (2008) 62, 594–599 133Bird AR, Brown IL, Topping DL. Starch, resistant starch, the gut microflora and human health. Current Issues Int Micro . 2000;1:25-37. 134 Pendyala S, Walker JM, and Holt PR. A High-Fat Diet Is Associated With Endotoxemia That Originates From the Gut. Gastroenterology 2012;142:1100–1101 135 Bala S, Marcos M, Gattu A, Catalano D, Szabo G.Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS One. 2014 May 14;9(5):e96864.

66

136 A. Piendl and M. Biendl, Freising-WeihenstephanPhysiological significance of polyphenols and hop bitters in beer. Brauwelt International Technical Feature 137 Yeh CC, Kao SJ, Lin CC, Wang SD, Liu CJ, Kao ST. The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro. Life Sci. 2007 Apr 24;80(20):1821-31. 138 Bosenberg, A.T., Brock-Utne, J.G., GaYn, S.L., Wells, M.T., Blake, G.T., Strenuous exercise causes systemic endotoxemia. Journal of Applied Physiology 1988; 65, 106–108. 139 Brock-Utne, J.G., GaYn, S.L., Wells, M.T., Gathiram, P., Sohar, E., James, M.F., et al. Endotoxemia in exhausted runners after a long-distance race. South African Medical Journal 1988; 73, 533–536. 140 Camus, G., Poortmans, J., Nys, M., Deby-Dupont, G., Duchateau, J., Deby, C., et al., 1997. Mild endotoxemia and the inflammatory response induced by a marathon race. Clinical Science (London) 92, 415–422. 141Claus SP et al. The gut microbiotia: a major player in the toxicity of environmental pollutants. Biofilms and Microbiomes 2016 2 16003