The gut microbiota influences development and homeostasis of the mammalian immune system, and is associated with human inflammatory and immune diseases as well as responses to immunotherapy. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging.
Here we study hundreds of hospitalized—and closely monitored—patients with cancer receiving haematopoietic 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, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics.
High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota—together 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.