The gut microbiota influences how circulating immune cells in humans change from one day to the next

The gut microbiota influences the development and homeostasis of the mammalian immune system, can alter immune cell compositions in mice, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells. Still, our understanding of how the microbiota modulates circulatory immune cells 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 circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously over time with unprecedented resolution. We analyzed daily changes in white blood cell counts from 2,235 patients, and 10,680 longitudinal fecal microbiota samples to identify bacterial genera consistently associated with those changes. Bayesian inference and validation across different patient cohorts revealed consistent associations between intestinal bacteria and peripheral immune cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks between peripheral immune cells. The quantification of validated microbiota associations enabled us to contrast the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism, and this way estimate the microbiota potential to alter peripheral immune cell dynamics directly in patients. Our analysis establishes and quantifies the link between the intestinal microbiota and immune cell dynamics in humans, with implications for microbiota-driven modulation of immunity and immunotherapies that rely on circulatory immune cells.