Overconsumption of low-digestible sugars can increase susceptibility to Salmonella Typhimurium infection

Abstract

Low-digestible carbohydrates (LDCs), including dietary fibers and sugars that resist absorption, are generally considered beneficial for the gut microbiota. However, we show that acute overconsumption of certain LDCs, particularly low-digestible sugars (LDSs), such as arabinose, lactulose, and polyols commonly used as sugar substitutes, can compromise colonization resistance against the common foodborne pathogen Salmonella enterica serovar Typhimurium. LDS overconsumption results in elevated fecal pathogen loads, systemic dissemination, and colitis in infected mice. Mechanistic analysis of arabinose overconsumption revealed that rapid fermentation acidifies the intestinal environment, perturbs the microbiota, alters gut-luminal short-chain fatty acid levels and elevated amino acid availability, which can support pathogen growth. Additionally, this perturbation impacts virulence by broadening tissue tropism (e.g. expansion to small intestine) and selecting for invasive Salmonella . Unlike antibiotic perturbations, Salmonella colonization requires SPI-1 and SPI-2 Type-III-secretion systems, linking virulence to pathogen fitness. These findings reveal how dietary perturbations can impact the gut ecosystem in ways that not only compromise colonization resistance but also enhance pathogen virulence.

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BibTeX RIS

BibTeX

@article{nguyen2026overconsumption,
  title = {{Overconsumption of low-digestible sugars can increase susceptibility to Salmonella Typhimurium infection}},
  author = {Bidong D. Nguyen and Sandra Y. Wotzka and Lisa Maier and Céline Fetz and Yves Steiger and Sanne Kroon and Elena F. Verdu and Nermin Akduman and Markus Arnoldini and Dorothée L. Berthold and Annika Hausmann and Camille Schmid and Patrick Kiefer and Philipp Christen and Manja Barthel and Lea Fuchs and Andreas Sichert and Ersin Gül and Emma Slack and Julia A. Vorholt and Wolf-Dietrich Hardt},
  journal = {Nature Communications},
  year = {2026},
  month = nov,
  doi = {10.1038/s41467-026-78218-0},
  url = {https://www.nature.com/articles/s41467-026-78218-0},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Overconsumption of low-digestible sugars can increase susceptibility to Salmonella Typhimurium infection
AU  - Bidong D. Nguyen
AU  - Sandra Y. Wotzka
AU  - Lisa Maier
AU  - Céline Fetz
AU  - Yves Steiger
AU  - Sanne Kroon
AU  - Elena F. Verdu
AU  - Nermin Akduman
AU  - Markus Arnoldini
AU  - Dorothée L. Berthold
AU  - Annika Hausmann
AU  - Camille Schmid
AU  - Patrick Kiefer
AU  - Philipp Christen
AU  - Manja Barthel
AU  - Lea Fuchs
AU  - Andreas Sichert
AU  - Ersin Gül
AU  - Emma Slack
AU  - Julia A. Vorholt
AU  - Wolf-Dietrich Hardt
PY  - 2026
DA  - 2026/11/03
JO  - Nature Communications
DO  - 10.1038/s41467-026-78218-0
UR  - https://www.nature.com/articles/s41467-026-78218-0
AB  - Low-digestible carbohydrates (LDCs), including dietary fibers and sugars that resist absorption, are generally considered beneficial for the gut microbiota. However, we show that acute overconsumption of certain LDCs, particularly low-digestible sugars (LDSs), such as arabinose, lactulose, and polyols commonly used as sugar substitutes, can compromise colonization resistance against the common foodborne pathogen Salmonella enterica serovar Typhimurium. LDS overconsumption results in elevated fecal pathogen loads, systemic dissemination, and colitis in infected mice. Mechanistic analysis of arabinose overconsumption revealed that rapid fermentation acidifies the intestinal environment, perturbs the microbiota, alters gut-luminal short-chain fatty acid levels and elevated amino acid availability, which can support pathogen growth. Additionally, this perturbation impacts virulence by broadening tissue tropism (e.g. expansion to small intestine) and selecting for invasive Salmonella . Unlike antibiotic perturbations, Salmonella colonization requires SPI-1 and SPI-2 Type-III-secretion systems, linking virulence to pathogen fitness. These findings reveal how dietary perturbations can impact the gut ecosystem in ways that not only compromise colonization resistance but also enhance pathogen virulence.
SN  - 2041-1723
ER  -

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