RT Journal Article SR Electronic T1 Hematopoietic stem and progenitor cells integrate Bacteroides-derived innate immune signals to promote gut tissue repair JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.05.463122 DO 10.1101/2021.10.05.463122 A1 Yoshikazu Hayashi A1 Maiko Sezaki A1 Gaku Nakato A1 Subinoy Biswas A1 Tatsuya Morishima A1 Md Fakruddin A1 Jieun Moon A1 Soyeon Ahn A1 Pilhan Kim A1 Yuji Miyamoto A1 Hideo Baba A1 Shinji Fukuda A1 Hitoshi Takizawa YR 2021 UL http://biorxiv.org/content/early/2021/10/06/2021.10.05.463122.abstract 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.