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 alters the entire microbiotic landscape. Previously we 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, at least in part, due 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, in both mice and humans, to be a key mechanism in the control of auto-reactivity in the immune system. Thus, we found a direct connection between probiotic treatment and one of the principal mechanisms for controlling excess immune responses that we know of.