PT - JOURNAL ARTICLE AU - Yoshikazu Hayashi AU - Maiko Sezaki AU - Gaku Nakato AU - Subinoy Biswas AU - Tatsuya Morishima AU - Md Fakruddin AU - Jieun Moon AU - Soyeon Ahn AU - Pilhan Kim AU - Yuji Miyamoto AU - Hideo Baba AU - Shinji Fukuda AU - Hitoshi Takizawa TI - Hematopoietic stem and progenitor cells integrate <em>Bacteroides</em>-derived innate immune signals to promote gut tissue repair AID - 10.1101/2021.10.05.463122 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.10.05.463122 4099 - http://biorxiv.org/content/early/2021/10/06/2021.10.05.463122.short 4100 - http://biorxiv.org/content/early/2021/10/06/2021.10.05.463122.full AB - Bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) are often activated by bacterial insults to replenish the host hemato-immune system, but how they integrate the associated tissue damage signals to initiate distal tissue repair is largely unknown. Here, we showed that acute gut inflammation expands HSPCs in the BM through GM-CSFR activation, and directs them to inflamed mesenteric lymph nodes for further differentiation into myeloid cells specialized in gut tissue repair. We also identified that this process is exclusively mediated by Bacteroides, a commensal gram-negative bacteria, that activates innate immune signaling. In contrast, chronic gut inflammation reduces HSC potential for hematopoietic reconstitution and immune response against infection. Similarly, microbial signals contribute to aging-associated HSPC expansion. These findings establish a cross-organ communication that promotes tissue regeneration, but if sustained, impairs tissue homeostasis that may be relevant to aging and chronic disorders.Summary The infiltrating microbiota Bacteroides upon acute colitis directed MPP migration from the BM to the MLN for their subsequent expansion and differentiation into tissue-repairing Ly6C+/G+ cells, whereas chronic colitis impairs HSC functionality similarly as aging.Competing Interest StatementThe authors have declared no competing interest.