Diet has a significant impact on shaping the gut microbiota composition according to this study. Researchers found that placing mice on different diets (low-fat vs high-fat/high-sugar) caused their gut microbiota to cluster more by diet than by host genotype. Even for mice with the same genotype, diet dominated in determining microbiota profile. When diets were alternated, the microbiota responded rapidly but showed some lag effects. The study demonstrates the outsized role of diet relative to host genetics in shaping the gut microbiome.

1. Alireza
Journal 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

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

3. Facts
● In human population, the gut microbiota is
dominated by 70 Bacterial species
● For the most part species and strains are stable
over years

4. 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.

5. 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

6. Potential Answers
● Host genotype

7. Potential Answers
● Host genotype
– It is shown that has a measurable impact on GM
– Does not explain inter-indevidual variation (mono-
zygotic twins)

8. Potential Answers
● Host genotype
– It is shown that has a measurable impact on GM
– Does not explain inter-indevidual variation (mono-
zygotic twins)
● Diet

9. 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 ?

10. Experiment 1
● 73 mice representing 5 inbred mouse with
established role in shaping gut microbiota (7-20
mice/genotype;3-9 cages/genotype)

11. 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)

12. 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)

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

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

16. Same Genetic / Same Diet / Same
gender

17. Experiment 2
● More than 200 Diversity Outbred (DO) mouse
● Low-Fat, High-plant polysaccharide diet (LFPP)
● High-Fat, High-sugar diet (HFHS)

18. Temporal dynamic of diet-induced
microbiome
● Study the consequence of repeated dietary
disturbances on community composition using the
outbred mice

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

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

21. Oscillating Diets 1

22. Oscillating Diets 2
● Two groups of mice on oscillating diets stagged by
3 days.

24. 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

25. ● Predicted functional profiling of microbiome using
their 16sRNA data
● Identified 47 clusters of orthologous groups

27. 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.