microbiome and bacterial-overgrowth (sibo and ibs) · microbiome and bacterial-overgrowth (sibo and...

Microbiome and Bacterial-Overgrowth

(SIBO and IBS)

Bible Class

15th oct. 2014

Universitätsklinik für Viszerale Chirurgie und Medizin

Universitätsklinik für Viszerale Chirurgie und Medizin / www.chirurgiebern.ch

Content – Overview - Topics

The microbiome:

Nomenclature

Background information

Related clinical problems

Small-intestinal-bacterial overgrowth:

Diagnostics

Treatment


MICROBIOME


Microbiome - Nomenclature

Symbiosis =

Commensalism =

Parasitism =

Competition =



Symbiosis =

Commensalism =

Parasitism =

Competition =

win-win

win-zero

win-loose

loose-loose



Formal rank

Example Numbers

Domain Bacteria

Phylum Proteobacteria > 50

Class Gamma-Proteobacteria 5

Order Enterobacteriales 15

Family Enterobacteriacea 1

Genus Escherichia >50

Species E.coli > 10

Subspecies EIEC - serotypes > 100


What proportion of microbiome – species can be

cultured ?

Less than 20 %

Techniques to study human microbiome ?

16rRNS: who is out /in there ?

Metagenomics: what genes are present in those bacteria ?

Meta-Transcriptomics/Proteomics: what are they doing ?



Alpha-Diversity = Bacterial/Species richness

Beta-Diversity = Number of Taxa unique for the ecosystem

Simpson Diversity Index

Sorensen Similarity Index


Dysbiosis: «Index»

NOT standardized medical term

refers to microbial imbalance

e.g.


[total abundance in organisms increased in CD]

[total abundance of organisms decreased in CD]

Or

“Good”

“Bad”

Gevers et al. Cell Host Microbe 2014

Bajaj et al. Jhepatol. 2014


Dysbiosis: «Index»

NOT standardized medical term

refers to microbial imbalance

e.g.


[total abundance in organisms increased in CD]

[total abundance of organisms decreased in CD]

Or

“Good”

“Bad”


Bajaj et al. Jhepatol. 2014

high MD-index >1 in most cases

strong reduction in the species richness


In principle, a healthy microbiota is defined

by high diversity and an ability to resist

change under physiological stress.

In contrast, microbiota associated with

disease is defined by lower species diversity,

fewer beneficial microbes and/or the

presence of pathobionts.

Role of Dysbiosis for Disease Processes ?


How many times more bacteria than host cells

usually life within the human gut

containing how much genomic information ?

Numbers: 10 times !!

Genomic information: 100 times


„Normal“ Microbiota across intestinal wall

Kim YS et al. Curr Opin Gastro 2010

Lumen

Inner Layer Mucus

Outer Layer Mucus

Gu

t F

lora

Com

part

ments


Juge N. Trends Microbiol. 2012 ;20(1):30-9

Removable by aspiration

Too firm To be removed

Mucus Layers across intestinal wall


At which intervals do bacteria replicate in-vivo ?

(e.g. in mice mono-colonised with E.coli)

Lumen – Colon:

Mucus – Colon:

every 8 -10 hours

every (1-) 2 hours


What are the main phyla in human colon

Firmicutes

Bacteroidetes

Actinobacteria


Enterotypes of the human gut microbiome

Arumugam et al. Nature 2011

39 individuals (fecal samples), 4 european countries

Assessing phylogenetic composition


Organ-System

Evidence for role of microbiome

«Dysbiosis»

Infections Clostridium difficile √ √

Metabolism Obesity

Diabetes type -2

√

√

√

√

Gastrointestinal IBD

IBS

Coeliac disease

√

√

√

√

√

√

Liver Fibrogenesis/corrhosis

complications of cirrhosis

(e.g. SBP, HE, HRS)

NASH, ASH

√

√

√

√

√

√

√

√

Evidence of microbiome involvement in diseases


Organ-System

Evidence for role

of microbiome

Gefäss-system Atherosklerose

Hematology ITP

Brain/Neurology Multiple Sclerosis

Parkinson

Depression

Autism, Schizophrenia

Carcinogenesis HCC

KRCa

Evidence of microbiome involvement in diseases

√

√ √ √ √ √ √ √

Atopic dermatitis, rhinitis, poylcystic ovar, chronic pain/fatigue syndrome,

HIV, Antiphospholipid-syndrome…………………………


What do we need bacteria in the gut for ?

Salvage energy

Providing Vitamins

Colonization resistance

Shaping immune function

Brain function ?

Modulation/metabolization Xenobiotics


Intrinsic:

- Motility

- GI-secretions (acid…)

- Genes (e.g. NOD2)….

- Antimicrobial peptides

- Immunity (sIgA)

What factors modulate the microbiome

(quantitative and qualitative) ?


Intrinsic:

- Motility

- GI-secretions (acid…)

- Genes (e.g. NOD2)….

- Antimicrobial peptides

- Immunity (sIgA)

What factors modulate the microbiome

(quantitative and qualitative) ?

Extrinsic:

- Diet, C2, Pre-/Pro-biotics

- Medications (PPIs, Antibiotics

- Procinetiks, Opioids……

- Stress

- Hygiene


Microbiome

Complexity + Stability

Probalbility of

Dysbiosis and Disease

HE

ALT

HY

DIS

TU

RB

ED

Physiological

Functions: Disease

Entities:

Modulators of Microbiome

Salvage

energy

Supply

vitamins

Modualte

Xenobiotic

compounds

Shaping human

Immune system

Modulating

Brain function

Genetics Hygiene

Stress

Birth

Route

Diet

Nutrition Drugs

Clostridium

Difficile Infection

Inflammatory

Bowel disease

(UC, MC)

Irritable bowel

syndrome

Bacterial

Overgrowth

NASH

Liver Cirrhosis

Metabolic

Syndrome

Obesity

Modulators, Function and Diseases related to Microbiome

Wiest R et al. in Press


S I B O


„Normal“ Microbiota along GI-Tract

Qu

an

tity


What is the definition of SIBO ?

>105

colony forming unit/ml

jejunal cultures and/or

with colonic-type bacteria


Breath-Testing for SIBO

How does it work ?

13C-D-Xylose Breath-test

H2-Breath-tests (Glukose, Laktulose)

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.klinikum.uni-heidelberg.de/Glukose-Atemtest.103703.0.html&ei=VIU9VNTmGY6-PP7pgNAF&bvm=bv.77412846,d.bGQ&psig=AFQjCNHf7fvgj2fHSHGvR7gqxYB8U8inzw&ust=1413404356492305

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.klinikum.uni-heidelberg.de/Glukose-Atemtest.103703.0.html&ei=VIU9VNTmGY6-PP7pgNAF&bvm=bv.77412846,d.bGQ&psig=AFQjCNHf7fvgj2fHSHGvR7gqxYB8U8inzw&ust=1413404356492305


Breath-Testing for SIBO

Caveats to consider ?

Yu et al. Gut 2011

False positive:

Malabsorption in small intestine->

+ rapid transit to colon-> fermentation

Contamination (oral flora)

False negative:

Bacteria: NO metabolizing encymes ?

Gastroparesis

Non-H2-Producer (10%)


Sensitivity

Specificity

Glucose-H2-test

40% 80%

Lactulose-H2-test

16-31% 86%

Breath-Testing for SIBO: vs. Gold Standard

Ghosal et al. J Neurogastroenterol Motil 2011;17:312-317)

up to 85% of healthy individuals have an abnormal LHBT

Am J Gastroenterol 2008;103:958 –963


Current Diagnosis of SIBO – Evidence ?

Meta-Analysis of 71 papers on SIBO in humans

Aim: assess validity of culture + other diagnostic tests

“….not even culture studies met the quality standards

described by Reid et al. ………..”

Khoshini R et al. DigDisSci 2008

Goldstandard:

Endoscopic aspiration upper

jejunum/distal duodenum

Rubins catheter (sterile plugged tip)

Aerobic (and anaerobic) culture


Pathophysiology - Mechanisms of SIBO

Factor preventing

SIBO

Disease/State

Promoting SIBO

Peristalsis

Gastric acid

Bile acids

Proteolytic encymes

Antimicrobial peptides,

Mucus ?, IgA?



Factor preventing

SIBO

Disease/State

Promoting SIBO

Peristalsis

Gastric acid

Bile acids

Proteolytic encymes


Mucus ?, IgA?

Stasis

Hypo/Anacidity

Cholestasis

Pankreatitis

?



Factor preventing

SIBO

Disease/State

Promoting SIBO

Peristalsis

Gastric acid

Bile acids

Proteolytic encymes


Mucus ?, IgA?

Mechanical obstruction

(post-surgery, -radiation etc.)

Motility disorder

(DM, Scleroderma, …..

Megaduodenum

Stasis in blind loops

PPI-use, atrophic gastritis

Bile outflow-obstruction

Any cause (tumor…..)

Immunological factors:

Hypo-, A-

gammaglobulinemia

AIDS

Chronic pancreatitis

Stasis

Hypo/Anacidity

Cholestasis

Pankreatitis

?



Factor preventing

SIBO

Disease/State

Promoting SIBO

Peristalsis

Gastric acid

Bile acids

Proteolytic encymes


Mucus ?, IgA?

Extra-Intestinal Reservoir, unclassified causes:

Liver cirrhosis, NASH, Cystic fibrosis, renal insufficiency, Cholangitis, enterocolic fistula

…………………………………………………………………………………………………….

Mechanical obstruction

(post-surgery, -radiation etc.)

Motility disorder

(DM, Scleroderma, …..

Megaduodenum

Stasis in blind loops

PPI-use, atrophic gastritis

Bile outflow-obstruction

Any cause (tumor…..)

Immunological factors:

Hypo-, A-

gammaglobulinemia

AIDS

Chronic pancreatitis

Stasis

Hypo/Anacidity

Cholestasis

Pankreatitis

?


Clinical consequences of SIBO ?

Malassimilation-syndrome due to:

Luminal Maldigestion AND Epithelial Malabsorption

Bile acid deconjugation -> Steatorrhoe

Epithelial injury due to «toxic» deconjugated Bile acids

Bacterial metabolization of US-SCFA-> hydroxy-FA-> diarrhoe

degradation of proteins, inhibition aminoacid absorption-> protein-loosing

Bacterial binding Vitamin B12-> reduced resorption-> anemia

Gas production: bloating, meteorism

Others:

peripheral neuropathy, tetany, osteomalacia, night blindness, dermatitis

Liver injury, nephro-toxicity, arthritis (predom. Jejunum-Ileum-Bypass)


Treatment of SIBO - How do you do it ?

Rifaximin: e.g. 1200mg/day

Ciproxin: e.g. 1000mg/day (+ Metronidazol)

SDD (Polymyxin+Gentamycin): e.g. 4 x 2 capsules


Shah et al. APT 2013 Meta-Analysis

Treatment of SIBO - Meta-Analysis


Human Intestinal Community Project


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microbiome and bacterial-overgrowth (sibo and ibs) · microbiome and bacterial-overgrowth (sibo and...

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