Nutrient landscape shapes the genetic diversification of the human gut commensal Bacteroides thetaiotaomicron

Lang, M.; Zioutis, C.; Heberlein, A.; Ivanovova, N.; Schwarz, J.; Koestlbacher, S.; Bochkareva, O.; Flanagan, K. J.; Pereira, F. C.; Berry, D.

doi:10.1101/2025.06.24.661248

bioRxiv · 10.1101/2025.06.24.661248

Nutrient landscape shapes the genetic diversification of the human gut commensal Bacteroides thetaiotaomicron

Lang, M.·Zioutis, C.·Heberlein, A.·Ivanovova, N.·Schwarz, J.·Koestlbacher, S.·Bochkareva, O.·Flanagan, K. J.·Pereira, F. C.·Berry, D.

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Abstract

Bacteroides thetaiotaomicron is a prominent member of the human gut microbiome that has evolved a suite of polysaccharide utilization loci (PUL) to break down a range of diet- and host-derived glycans. To gain insight into the evolution of this bacterium on ecologically meaningful time scales, we carried out an in vitro evolution study in which B. thetaiotaomicron was cultivated on media of different carbohydrate complexity for three months. Shotgun sequencing of the evolved populations revealed an increased number of single nucleotide polymorphisms with increased medium complexity, suggesting that genetic diversification is driven in part by the nutrient landscape. We also observed high-frequency reversible DNA inversions mediated by site-specific DNA integrases, which may be important to production and maintenance of phenotypic heterogeneity in the population. Competition experiments against the ancestor revealed adaption to the experimental conditions, with a fitness gain of the evolved populations and lineages thereof. This fitness advantage was accompanied by an increase in cell size, faster glucose depletion rates, and increased amylopectin degradation in the presence of glucose. In conclusion, rapid adaptive genetic diversification in B. thetaiotaomicron is induced and maintained in part by a complex nutritional environment.

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Lang, M., Zioutis, C., Heberlein, A., Ivanovova, N., Schwarz, J., Koestlbacher, S., Bochkareva, O., Flanagan, K. J., Pereira, F. C., Berry, D.. 2025-06-24. Nutrient landscape shapes the genetic diversification of the human gut commensal Bacteroides thetaiotaomicron. https://doi.org/10.1101/2025.06.24.661248

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