Skip to main content

ORIGINAL RESEARCH article

Front. Genet.
Sec. Immunogenetics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1502832
This article is part of the Research Topic Transcription Factors as Regulators of Adaptive Immunity View all articles

Global deletion of the immune cell transcription factor, T-bet, alters gut microbiota and insulin sensitivity in mice

Provisionally accepted
Emilie Stolarczyk Emilie Stolarczyk 1,2C T. Vong C T. Vong 1Natividad Garrido Mesa Natividad Garrido Mesa 1,3Ellen Marks Ellen Marks 1Donia Abdel-Aziz Donia Abdel-Aziz 1Qizi Ju Qizi Ju 1Ian Jackson Ian Jackson 1Nicholas Powell Nicholas Powell 1,4Graham M. Lord Graham M. Lord 1Jane K. Howard Jane K. Howard 1*
  • 1 King's College London, London, United Kingdom
  • 2 Abcam (United Kingdom), Cambridge, United Kingdom
  • 3 Kingston University, Kingston upon Thames, England, United Kingdom
  • 4 Imperial College London, London, England, United Kingdom

The final, formatted version of the article will be published soon.

    The gut microbiota plays a role in energy homeostasis: its composition differs in lean and obese mice and may impact insulin sensitivity. The immune system has co-evolved with the gut microbiota, but direct regulation of microbial communities by the immune system and its metabolic impact is unclear. Mice lacking the immune cell specific transcription factor T-bet (Tbx21) are insulin sensitive. Compared with wild-type mice, T-bet deficient mice were found to have a higher proportion of colonic regulatory T cells despite significantly fewer colonic T cells, B cells and NK cells. Microbiota deletion by administration of antibiotics, increased colonic immune cell numbers. Furthermore, we report that T-bet -/-mice have an altered gut microbial composition and fecal shortchain fatty acid content, with an increase in butyrate production, compared with wild-type mice. Finally, in a proof-of concept study, we show that the enhanced insulin sensitivity observed in T-bet -/- mice is temporarily transmissible to antibiotic-treated wild-type mice through fecal transfer. Immune regulation of the gut microbiota by T-bet may be a novel pathway modulating insulin sensitivity.

    Keywords: T-bet, Gut Microbiota, insulin sensitivity, Glucose homeostasis, fecal transfer, colonic immunity, short-chain fatty acids

    Received: 27 Sep 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Stolarczyk, Vong, Garrido Mesa, Marks, Abdel-Aziz, Ju, Jackson, Powell, Lord and Howard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jane K. Howard, King's College London, London, United Kingdom

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.