The gut microbiota influences circulatory immune cell dynamics in humans

The gut microbiota influences the development and homeostasis of the mammalian immune system and can alter immune cell compositions in mice. However, our understanding of how the microbiota modulates immunity remains limited, particularly in humans where a lack of manipulative experiments makes inference challenging. Here we overcome this challenge by studying hundreds of hospitalized---and closely monitored---bone marrow transplantation patients as they recover from chemotherapy-induced immune ablation. This aggressive treatment causes large shifts in both white blood cell and microbiota populations allowing the relationships between the two to be studied simultaneously over time, with unprecedented resolution. Our analysis shows that the ecological diversity of the gut microbiota had an immunosuppressive effect on circulating lymphocyte counts similar in magnitude to that of anti-inflammatory and immunosuppressive drugs administered to cancer patients. Moreover, by controlling for drug treatments and clinical metadata, we identified several microbiota components strongly associated with white blood cell dynamics: Streptococcaceae associated with lymphocyte increase and Actinomycetaceae with lymphocyte suppression, Prevotellaceae with monocyte increase and Enterobacteriaceae with monocyte suppression, Ruminococcaceae with neutrophil increase and Lachnospiraceae and Bacteroidaceae with neutrophil suppression. Our analysis establishes a direct link between the intestinal microbiota and systemic immunity in humans, with implications on clinical outcomes and microbiota-based therapies.