Diet leaves a genetic signature in a keystone member of the gut microbiota

Đapa, Tanja; Ramiro, Ricardo S.; Pedro, Miguel F.; Gordo, Isabel; Xavier, Karina B.

doi:10.1016/j.chom.2022.01.002

Cited by 58 publications

(69 citation statements)

References 115 publications

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“…Consistent with previous observations in other bacterial species (1)(2)(3)(4), we found that a handful of lineages expanded to intermediate frequencies (>1%) in vivo by day 16 (Fig. 1B-E), indicating rapid positive selection on a subset of the lineages.…”

supporting

confidence: 92%

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Wong

Good

2022

Preprint

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Gut microbiota can adapt to their host environment by rapidly acquiring new mutations. However, the dynamics of this process are difficult to characterize in dominant gut species in their complex in vivo environment. Here we show that the fine-scale dynamics of genome-wide transposon libraries can enable quantitative inferences of these in vivo evolutionary forces. By analyzing >400,000 lineages across four human Bacteroides strains in gnotobiotic mice, we observed positive selection on thousands of previously hidden mutations – most of which were unrelated to their original gene knockouts. The spectrum of fitness benefits varied between species, and displayed diverse tradeoffs over time and in different dietary conditions. These results suggest that within-host adaptations arise from an intense competition between numerous contending mutations, which can strongly influence their emergent evolutionary tradeoffs.

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supporting

confidence: 92%

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Wong

Good

2022

Preprint

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“…In this study, we analyzed the composition of intestinal microbiota in six GIT regions of 8 healthy individual macaques. The current study also found that age affects the composition of the gut microbiota ( 20 , 21 ). In our study, the 8 macaques (7 males and 1 female) were 13 to 16 years old.…”

Section: Discussionsupporting

confidence: 72%

The Lumenal Microbiota Varies Biogeographically in the Gastrointestinal Tract of Rhesus Macaques

et al. 2022

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“…Feeding mice which are stably monocolonized with B. theta a fiber-less high-fat diet imposes a surprisingly mild bottleneck on the B. theta population 3 days after treatment, even though this intervention has been shown to increase bile acid concentrations to levels that inhibit B. theta growth (Wotzka et al, 2019). As it has been shown that B.theta rapidly evolves to adapt to dietary challenges in the context of a resident microbiota (Dapa et al, 2022), the observed mild population bottleneck imposed by high-fat diet feeding might only manifest if B. theta competes against other gut microbiota members, potentially ones that are more resistant to bile salts (e.g., E. coli , see Wotzka et al, 2019). When infecting mice that are stably monocolonized with B. theta with Salmonella, we observed a larger decrease in B. theta clonal survival probability, which is consistent with the sensitivity of commensal species to gut inflammation (cite Stecher et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide is dependent on the resident microbiota

Hoces

Greter

Arnoldini

et al. 2022

Preprint

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Many microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. However, we remain largely blind to the quantitative effects of processes determining colonization success. In this study, we used genetically-barcoded Bacteroides thetaiotaomicron (B.theta) strains in combination with mathematical modeling to quantify population bottlenecks experienced by B.theta during gut colonization. Integrating population bottlenecks sizes with careful quantification of net growth rates in vitro and in vivo allows us to build models describing the events during intestinal colonization in the context of gnotobiotic and complex microbiotas. Using these models, we estimated the decrease in niche size for B.theta colonization with increasing microbiota complexity. In addition, our system can be applied to mechanistically dissect colonization defects of mutant strains. As a proof of concept, we demonstrated that the competitive disadvantage of a B.theta mutant lacking capsular polysaccharide is due to a combination of an increased lag-phase before growth initiation in the gut, combined with an increased clearance rate. Crucially, the requirement for the B.theta capsule depended strongly on microbiota composition, suggesting that the dominant role may be protection from bacterial or phage aggression rather than from host-induced bactericidal mechanisms.

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Diet leaves a genetic signature in a keystone member of the gut microbiota

Cited by 58 publications

References 115 publications

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking

The Lumenal Microbiota Varies Biogeographically in the Gastrointestinal Tract of Rhesus Macaques

Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide is dependent on the resident microbiota

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