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?