Microbiome

Question 1

What is hygiene hypothesis?

Answer 1

Born relatively sterile==>Generate normal micro biome
Born into “sanitized environment” with abx=>develop abnormal microbiome==>immune mediated diseases (Crohn’s, asthma, metabolic syndromes)

Question 2

What is relationship between abx use and development of obesity in mice?

Answer 2

Mouse given low-dose penicillin early in life (leads to disrupted microbiota) increases loss of early-life protective bacteria and leaves mouse more prone to obesity. When this mouse’s microbiota is transferred to a germ-free mouse, it then is more likely to develop obesity.

Question 3

How much of IBD is due to genetic contribution?

What are implications

Answer 3

Crohn’s=30-40%

Since environmental factors are largest contributor, should target environment for change.

Question 4

What changes do we see in gut microbiota (dysbiosis) in IBD?

Answer 4

Inflammation leads to hyperemia and bleeding into lumen of GI tract, which results in increase in proteobacteria and actinobacteria.

They are generally aerotolerant and able to manage oxidative stress. They are more injurious?

Question 5

What happens when you decrease gut micro biome richness?

What type of diet is associated with increased bacterial gene richness?

Answer 5

Decreased richness (aka biodiversity) is associated with disease states and Westernized diets.

Increased consumption of fruits/vegetables and energy-restricted diets are associated with bacterial gene richness.

Question 6

What is the effect of increased fatty diet on metabolite production and subsequent impact on disease

Answer 6

Increased fat==>choline==>Trimethyl amine (TMA)==>Converted to TMAO in liver ==> Contributes to atherosclerosis

Question 7

What is the significance of CutC?

Answer 7

CutC is a bacterial protein that converts choline to TMA.

Can be used to quantify risk for heart disease? Can be targeted for intervention via drugs or “medical foods”?

Question 8

Describe findings in microbiota in vegans vs. omnivores

Answer 8

Vastly different micro biome (can predict accurately using 30 different metabolites)

Vegans have greater contribution of micro biome to metabolome

Question 9

What is treatment for refractory C Diff?

Answer 9

Fecal transplant

Question 10

What are possible mechanisms for FMT in C Diff? (4)

Answer 10

Competitive niche exclusion for C Diff
Growth inhibition
Altered bile acid composition
Stimulates immune regulation