lecture 22 (4 21-2016) slides
TRANSCRIPT
Lecture 22:Diversity of the Human Microbiome
Microbiology 480Prof. Kristen DeAngelis
Spring 2016
Review and Exam IV
• Review– 1-2:30pm on Monday
May 2 in LSL N210– Bring questions!
• Exam IV– 10:30am on Tuesday
May 3 in Morrill III room 203 (regular classroom)
Objectives
• What is the human microbiome?– How many are there? Where do they live? How do they
differ among different people? Who are they? What do they do?
• How do you get your microbiome?• What is the correlation between microbiome and
health or disease?– Antibiotics, probiotics, prebiotics– Obesity, malnutrition
• What are the interactions between your microbiome and the built environment?
How many microbes are there?
1013 bacteria vs1013 human cells1-3% body mass
Revised estimates for the number of human and bacteria cells in the body
Sender et al. 2016
Revised estimates for the number of human and bacteria cells in the body
• New study published in 2016– Sender et al., doi:
http://dx.doi.org/10.1101/036103.
Sender et al. 2016
Human Microbiome Project
HMP Consortium, 2012
• Healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina.
Human Microbiome Project
HMP Consortium, 2012
• Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure
Human Microbiome Project
• Microbial community membership and function correlates with host phenotype and sample metadata.
• Ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata.
HMP Consortium, 2012
Global signature to the Human Microbiome
Who’s there?
• Human microbiome is mostly bacterial but also some fungal and other eukaryotic cells
Human microbiome
• Bacteria– Bacteroidetes dominate
gut communities– Firmicutes dominate
esophagus and vagina– Actinobacteria live in the
mouth, where they make biofilms (plaque)
– Cyanobacteria live in the hair
– Fusobacteria– Proteobacteria
• Archaea– dominant group are the
methanogens, particularly Methanobrevibacter smithii and Methanosphaera stadtmanae
– No archaeal pathogens are known
• Eukaryotes– Mostly fungi, e.g., yeasts like
Candida spp. – Yeasts are also present on the
skin, where they consume oils secreted from the sebaceous glands
Eukaryotes
*
Gut microbiome
Walter & Ley, 2011
Host lifestyle affects human microbiota on daily timescales
Gut microbiota make metabolites that are detrimental to the host
• Heterocyclic amines (HCAs) in char –converted by gut microbes to electrophilic derivatives which damage host DNA
• Sulfur reducers convert sulfur in high-protein diets to H2S, which also damages host DNA
Rooks & Garrett, F1000ReportsBiology, 2011
Gut microbiota make metabolites that are beneficial to the host
• Butyrate (product of starch fermentation) – energy source for gut wall epithelial cells
• Acetate (fermentation product) quells overactive immune response; may protect host from E. coli infections
• Proprionate (fermentation product) interacts with T cells, influences immune response
• Polyphenols metabolized by bacteria to antioxidants & anti-cancer compounds; e.g., ellagic acid (in berries & nuts)
Rooks & Garrett, F1000ReportsBiology, 2011
Gut microbiome
Walter & Ley, 2011
Gut microbiome
Brussow & Parkinson, 2014
• 1. Host relies on abilities of microbes to digest complex components & generate short-chain fatty acids (SCFAs)
Gut microbiome
• 2. Microbiota of the small intestine interact with the host immune system– IgA is an important tool for keeping pathogens in
check– IgA may shape the diversity of the gut microbiota– Little is known of the microbiota of the SI, or
interactions with the immune system
Walter & Ley, 2011
Gut microbiome
• 3. Development of the gut microbiome– Colonization history impacts microbial community
composition & diversity– Environmental & stochastic factors affect
community composition & diversity– Twins may have different microbial communities!
http://bit.ly/HumanMicrobiome
Gut microbiome
• 4. Diversity of the gut microbiome– Gut microbiota differ greatly between individuals
in membership & community structure– Microbiomes are functionally equivalent in
different individuals– Gut microbiota exhibit “phylogenetic clustering” –
rich species diversity in few phyla
Walter & Ley, 2011
Gut microbiome
• 5. Evolution of the gut microbiome– Human-microbiota symbiosis has evolved with
human cultural changes– Both indigenous microbes and new arrivals evolve
to occupy new niches = “in situ evolution”• Example: The Sushi Gene!
How does your microbiome affect health and disease?
• Antibiotics• Probiotics• Prebiotics• Obesity• Malnutrition
Martin Blaser, 2011. Nature.
Triclosan
Gaulke et al., bioRxiv 2016
Human microbiome and probiotics
• Fecal transplants
Human microbiome and probiotics
• Fecal transplants
• Although some probiotics have shown promise in research studies, strong scientific evidence to support specific uses of probiotics for most health conditions is lacking. The U.S. Food and Drug Administration (FDA) has not approved any probiotics for preventing or treating any health problem.
https://nccih.nih.gov/health/probiotics/introduction.htm
Microorganisms that are probiotics
• Bacteria– Lactobacillus spp. - – Bifidobacterium spp. -
• Eukarya– Saccharomyces boulardii - yeast
Sequencing of probiotics sold in US market
…
Patro et al., 2016 mSphere
Sequencing of probiotics sold in US market
…
Patro et al., 2016 mSphere
The original prebiotic: mother’s milk• Humans cannot digest many human milk oligosaccharides!• Selective for Bifidobacteria (phylum Actinobacteria)
– Activity of this group lowers gut pH– Makes it more difficult for Gram-negative bacteria to grow
Smilowitz et al., Annu. Rev. Nutr. 2014
A core gut microbiome in obese and lean twins
Turnbaugh et al., Nature 2009
A core gut microbiome in obese and lean twins
Turnbaugh et al., Nature 2009
Human microbiome and malnutrition
A malnourished child with
kwashiorkorTrehan et al. NEJM 2013.
Gut microbiomes of Malawian twin pairs discordant for kwashiorkor
Smith et al. Science. 2013.
Gut microbiomes of Malawian twin pairs discordant for kwashiorkor
Smith et al. Science. 2013.
Gut microbiome is a causal factor in kwashiorkor
Smith et al. Science. 2013.
Mouse model
KwashiorkorGut
communities
HealthyGut
communities
Microbiology of the built environment• People spend most of their time indoors• Understanding biogeography of the “built environment” is
motivated by public health• MicroBE.net
Diversity, distribution and sources of bacteria in residential kitchens
Flores et al., Env Micro 2012
Objectives
• What is the human microbiome?– How many are there? Where do they live? How do they
differ among different people? Who are they? What do they do?
• How do you get your microbiome?• What is the correlation between microbiome and
health or disease?– Antibiotics, probiotics, prebiotics– Obesity, malnutrition
• What are the interactions between your microbiome and the built environment?