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
- PubMed: 33077598
- DOI: 10.1073/pnas.1921223117
Study Design
- Type
- Clinical Trial
- Population
- Mice
- Methods
- In vivo experiment with mice
- Highly Cited
- Animal Study
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.