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Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade

  • 2020-10-19
  • Proceedings of the National Academy of Sciences 117(44)
    • Shan Sun
    • Lingjie Luo
    • Wenhua Liang
    • Qian Yin
    • Jing Guo
    • Anthony M. Rush
    • Z. Lv
    • Q. Liang
    • M. Fischbach
    • J. Sonnenburg
    • Dylan Dodd
    • Mark M. Davis
    • Feng Wang

Abstract

Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that Bifidobacterium could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that Bifidobacterium altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-dependent manner. Moreover, this altered commensal community enhanced both the mitochondrial fitness and the IL-10-mediated suppressive functions of intestinal Tregs, contributing to the amelioration of colitis during immune checkpoint blockade.

Keywords: Bifidobacterium; immune checkpoint blockade; metabolism; microbiota; regulatory T cell.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
BifidobacteriumEnhanced Mitochondrial Fitness of Intestinal Regulatory T-cellsBeneficial
Moderate
BifidobacteriumEnhanced Suppressive Function of Intestinal TregsBeneficial
Moderate
BifidobacteriumImproved Colitis SymptomsBeneficial
Moderate
BifidobacteriumReduced Intestinal ImmunopathologyBeneficial
Moderate
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