Dietary carbohydrates alter immune-modulatory functionalities and DNA inversions in Bacteroides thetaiotaomicron

Noa Gal-Mandelbaum, Shaqed Carasso, Alon Kedem, Tamar Ziv, Roni Keshet-David, Roberto Abboud, Rawan Zaatry, Tal Gefen and Naama Geva-Zatorsky ()
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Noa Gal-Mandelbaum: Technion-Israel Institute of Technology
Shaqed Carasso: Technion-Israel Institute of Technology
Alon Kedem: Technion-Israel Institute of Technology
Tamar Ziv: Technion-Israel Institute of Technology
Roni Keshet-David: Technion-Israel Institute of Technology
Roberto Abboud: Technion-Israel Institute of Technology
Rawan Zaatry: Technion-Israel Institute of Technology
Tal Gefen: Technion-Israel Institute of Technology
Naama Geva-Zatorsky: Technion-Israel Institute of Technology

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract The gut bacteria environment is highly dynamic. Environmental conditions were shown to affect microbial composition. Yet, their influences on bacterial functionality (e.g., immune-modulation activity) are mostly overlooked. Distinct strains of the same species, and even the same bacterial strain, may have different effects on the immune system depending on their growth environment. Therefore, studying the functionality of strains under different conditions is crucial. We analyzed functional alterations in the gut symbiont Bacteroides thetaiotaomicron (B. theta) under different dietary components consumption in humans, upon white sugar consumption in mice, and in response to 190 different carbon sources in vitro. Dietary alterations affected the orientation of phase variable regions in B. theta in humans, in vivo, and in vitro, and altered B. theta’s proteome and immune-modulatory functionality. Studying the effects of dietary components on the immune-modulatory functionalities of key members of the gut microbiota will allow for personalized dietary recommendations.

Date: 2025
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DOI: 10.1038/s41467-025-60202-9

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