The Gut Microbiota Is Associated With Immune Cell Dynamics in Humans

Abstract

The gut microbiota influences development1–3 and homeostasis4–7 of the mammalian immune system, and is associated with human inflammatory-8 and immune diseases9,10 as well as patients’ responses to immunotherapy11–14. Still, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans where a lack of deliberate manipulations makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—cancer patients receiving hematopoietic cell transplantation as they recover from chemotherapy and stem cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and 10,680 longitudinal microbiota samples from patients revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the potency of bacterial genera to immunomodulatory medications, revealing a considerable influence of the gut microbiota—in concert and over time—on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.