• Jonas Schluter, Jonathan U Peled, Bradford P Taylor, Kate A Markey, Melody Smith, Ying Taur, Rene Niehus, Anna Staffas, Anqi Dai, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Sejal Morjaria, Maly Fenelus, Melissa S Pessin, Nelson J Chao, Meagan Lew, Lauren Bohannon, Amy Bush, Anthony D Sung, Tobias M Hohl, Miguel-Angel Perales, van den BrinkMarcel R MMRMhttp://orcid.org/0000-0003-0696-4401Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Weill Cornell Medical College, New York, NY, USA., and Joao B Xavier.
• Institute for Computational Medicine, NYU Langone Health, New York, NY, USA. jonas.schluter@nyulangone.org.
• Nature. 2020 Dec 1; 588 (7837): 303-307.

AbstractThe gut microbiota influences development1-3 and homeostasis4-7 of the mammalian immune system, and is associated with human inflammatory8 and immune diseases9,10 as well as responses to immunotherapy11-14. 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.

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