An association between the gut microbiota and immune cell dynamics in humans

Abstract

22The gut microbiota influences the development and homeostasis of the mammalian immune system 1-23 3 , can alter immune cell compositions in mice [4][5][6][7] , and is associated with responses to immunotherapy 24 that rely on the activity of peripheral immune cells [8][9][10][11][12] . Still, our understanding of how the microbiota 25 modulates circulatory immune cells remains limited, particularly in humans where a lack of 26 manipulative experiments makes inference challenging. Here we overcome this challenge by studying 27 hundreds of hospitalized-and closely monitored-bone marrow transplantation patients as they 28 recover from chemotherapy-induced immune ablation. This aggressive treatment causes large shifts in 29 both circulatory immune cell and microbiota populations, allowing the relationships between the two 30 to be studied simultaneously over time with unprecedented resolution. We analyzed daily changes in 31 white blood cell counts from 2,235 patients, and 10,680 longitudinal fecal microbiota samples to 32 identify bacterial genera consistently associated with those changes. Bayesian inference and 33 validation across different patient cohorts revealed consistent associations between intestinal bacteria 34 and peripheral immune cell dynamics in the context of immunomodulatory medications, clinical 35 metadata and homeostatic feedbacks between peripheral immune cells. The quantification of validated 36 microbiota associations enabled us to contrast the potency of fermentatively active, obligate anaerobic 37 bacteria with that of medications with known immunomodulatory mechanism, and this way estimate 38 the microbiota potential to alter peripheral immune cell dynamics directly in patients. Our analysis 39 establishes and quantifies the link between the intestinal microbiota and immune cell dynamics in 40 humans, with implications for microbiota-driven modulation of immunity and immunotherapies that 41 rely on circulatory immune cells. 42 3 MAIN TEXT 43

The Dynamic Landscape of Parasitaemia Dependent Intestinal Microbiota Shifting at Species Level and the Correlated Gut Transcriptome During Plasmodium Yoelii Infection

“…We also found a high correlation between certain intestinal microbiota and master transcription factors of host immunity during P. yoelii infection. Currently, we still cannot identify their causality [37]. The intestinal microbiota can produce serval metabolic repertoire as signal molecules, such as short-chain fatty acids (SCFAs), or increase the host product, such as bile acid, to regulate the phenotype of antiin ammatory cells [38][39][40].…”

The dynamic landscape of parasitaemia dependent intestinal microbiota shifting at species level and the correlated gut transcriptome during Plasmodiumyoeliiinfection

“…We also found a high correlation between certain intestinal microbiota and master transcription factors of host immunity during P. yoelii infection. Currently, we still cannot identify their causality [37]. The intestinal microbiota can produce serval metabolic repertoire as signal molecules, such as short-chain fatty acids (SCFAs), or increase the host product, such as bile acid, to regulate the phenotype of anti-inflammatory cells [38][39][40].…”

Microbial matters: modelling the complex web of host–microbiome interactions

“…Xavier's group is collaborating with clinicians to understand how antibiotics affect the gut microbiomes of bone-marrow-transplant recipients, whose immune systems are suppressed to minimize rejection of the transplant. They found that the resulting microbial disruptions can markedly affect the function of the immune system after the transplant, and that supplementing individuals with healthy microbial populations could improve their recovery 4 .…”