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

Significance Many millions of people take probiotics over the counter, but very little is known about what they do and whether they really work. Here we show that in mice, introducing Bifidobacterium , one of the most commonly used probiotics, not only colonizes the gut, but also alters the entire microbiotic landscape. We previously found that this treatment rescues mice from an otherwise fatal inflammatory syndrome brought on by anti–CTLA-4 antibody, a checkpoint inhibitor that often causes autoimmunity in humans undergoing cancer treatment. Here we show that this is effect is due, at least in part, to the effect of this probiotic treatment on regulatory CD4 + cells, whose metabolic and immune suppressive functions are altered. These CD4 + regulatory T cells are known to be a key mechanism in the control of autoreactivity in the immune system in both mice and humans. Thus, we found a direct connection between probiotic treatment and one of the known principal mechanisms for controlling excess immune responses.