AlirezaJournal Club, March 20

Diet dominates host genotype in shaping the murine gut microbiota

Carmody RN, Gerber GK, Luevano JM Jr, Gatti DM, Somes L, Svenson KL, Turnbaugh PJ.

Cell Host Microbe. 2015 Jan

Facts

● In human population, the gut microbiota is dominated by 70 Bacterial species

Facts

● In human population, the gut microbiota is dominated by 70 Bacterial species

● For the most part species and strains are stable over years

Facts

● In human population, the gut microbiota is dominated by 70 Bacterial species

● For the most part species and strains are stable over years

● The community membership and relative abundance of members differers markedly among individuals.

Facts

● In human population, the gut microbiota is dominated by 70 Bacterial species

● For the most part species and strains are stable over years● The community membership and relative abundance of members

differers markedly among individuals.

● What causes this substantial degree of inter-individual variation remains a key question in the field

Question

Potential Answers

● Host genotype

Potential Answers

● Host genotype– It is shown that has a measurable impact on GM

– Does not explain inter-indevidual variation (mono-zygotic twins)

Potential Answers

● Host genotype– It is shown that has a measurable impact on GM

– Does not explain inter-indevidual variation (mono-zygotic twins)

● Diet

Potential Answers

● Host genotype– It is shown that has a measurable impact on GM

– Does not explain inter-indevidual variation (mono-zygotic twins)

● Diet● Other factors ?

Experiment 1

● 73 mice representing 5 inbred mouse with established role in shaping gut microbiota (7-20 mice/genotype;3-9 cages/genotype)

Experiment 1

● 73 mice representing 5 inbred mouse with established role in shaping gut microbiota (7-20 mice/genotype;3-9 cages/genotype)

● Low-Fat, High-plant polysaccharide diet (LFPP)

Experiment 1

● 73 mice representing 5 inbred mouse with established role in shaping gut microbiota (7-20 mice/genotype;3-9 cages/genotype)

● Low-Fat, High-plant polysaccharide diet (LFPP)● High-Fat, High-sugar diet (HFHS)

HFHS diet shifts the GM; clear clustering by diet and sub clustering by genotype

● impact of the HFHS diet may depend on the broader host or microbial community context.

Same Genetic / Same Diet / Same gender

Experiment 2

● More than 200 Diversity Outbred (DO) mouse

● Low-Fat, High-plant polysaccharide diet (LFPP)● High-Fat, High-sugar diet (HFHS)

Temporal dynamic of diet-induced microbiome

● Study the consequence of repeated dietary disturbances on community composition using the outbred mice

HFHS diet shifts the GM; clear clustering by diet (wild type added)

Response to HFHS diet occurred fast (within 3)HFHS diet needed 1-2 weeks to respond to a second

HFHS disturbance.

Oscillating Diets 1

Oscillating Diets 2● Two groups of mice on oscillating diets stagged by

3 days.

Findings

● Gut microbiota was rapidly and consistently changed by the alternating diets, with most changes being reversible.

● 125 species-level OTU showed consistent responses● 32 OTUs showed hysteresis(lagging behind) in response● Clostridiales may be more active than the Bacteroidales

● Predicted functional profiling of microbiome using their 16sRNA data

● Identified 47 clusters of orthologous groups

Summary

● Extensive time series analyses● Role of beta-diversity● Mice, even if fed the same diet, show highly individualized

microbiome (cage, facility effects, etc)● In human studies, do not forget inter-subject variation● Dietary interventions could overcome heritable components● Diet in extreme case (LFPP to a HFHS) can dominate genotype !● importance of dietary history in shaping gut microbiome

structure.