Microbial communities of the human digestive systemhuman digestive system

Allen RassaBi l 405Biology 4055/30/2008

Microbial Real EstateMicrobial Real Estate• 1014 bacterial cells in

digestive systemdigestive system• They keep us healthy (keep

pathogens away)pathogens away)• Microflora is like an organ• Confined to the inner tube• Confined to the inner tube• Is this a bioreactor?• Or a chemostat?• Or a chemostat?• Or a biofilm?

DominantDominant Community Membersof Colon or “Distal Gut”

Dethelfsen et al., 2007

Who is there?

Backhead et al., 2005

Why such low diversity???Why such low diversity???• Much lower diversity than an environmental sample• Anaerobic environment• Temperature and pH are static but things change

because of what we eat

• Specific Host immune system regulation can differentiate the good and bad ones. If this system is disrupted it leads to Chron’s Disease

• Viruses also regulate the proportions of microbial communities

Microbes help us extract nutrients• Ferment indigestible carbohydrates into di- and monosaccharides and short

chain fatty acidsO

FermentationIndigestible OHCarbohydrates

• Methanogenic Methanobrevibacter smithii will reduce the partial pressure of H2 and CO2

2H2 + CO2 CH4 +O2

Coevolution in our gutsCoevolution in our guts

Bacteroidetes thetaiotamicron isBacteroidetes thetaiotamicron is a prominant CFB in our digestive system.

It has a huge genome (6.3 Mb) which encodes 50 ECF sigma factors

Is able to respond to changes in host diet

Methanogenic Methanobrevibacter smithii is a close friend

Backhead et al., 2005

“Glycobiome” of B. thetaiotamicronGlycobiome of B. thetaiotamicron

Xu and Gordon, 2003

B Longum relies on B thetaiotamicronB. Longum relies on B. thetaiotamicron

Glycosylhydrolases encoded by the genomes of selected sequenced members of the adult human distal intestinal microbiota

Xu and Gordon, 2003

Human diseases and microfloraHuman diseases and microflora

• Cause or effect?Cause or effect?• Many disease are known to be caused by a

disruption of natural microbial populations indisruption of natural microbial populations in the distal gut

Ch ’ di d I it bl b l d– Chron’s disease and Irritable bowel syndrome (both autoimmune)Ob it– Obesity

Do microbes make us fat?Do microbes make us fat?

Normal mousel l i i C i

Obese mouseNearly Equal Firmicutes:CFB ratio High Firmicutes:CFB ratio

ProbioticsProbiotics

• Probiotics help us digest food• They are usually allochthonous• They are usually allochthonous• Important during antibiotic therapy

ConclusionConclusion

• Gut has relatively low diversity but highGut has relatively low diversity, but high population density

• Humans and their gut microbes are actually• Humans and their gut microbes are actually “superorganisms”H Mi bi P j b i l• Human Microbiome Project – bacterial genes in/on us outnumber our genes

• We are very dependent on our symbionts to keep us healthy and well-fed