4.8 Article

Selected commensals educate the intestinal vascular and immune system for immunocompetence

Journal

MICROBIOME
Volume 10, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s40168-022-01353-5

Keywords

Microbial consortia; Commensal imprinting; Asymptomatic infection; Endothelial cells; Blood vessel development; Intestinal maturation; Genome-guided microbiota; Neutrophils; C. rodentium; Oligo-Mouse-Microbiota; Colonization resistance; Enteric pathogen

Categories

Funding

  1. Projekt DEAL
  2. Jurgen Manchot Stiftung
  3. DFG Priority Programm [SPP1656, STE 776/3-1]
  4. Andre Bleich [BL 953/5-2]
  5. von Behring Rontgen Stiftung [66-0008]
  6. DFG [KFO 309 Z01, SFB1021 Z02, SFBTR84 B08]
  7. HMWK LOEWE Research Cluster Diffusible Signals project [B3]

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Colonization with selected commensal microbes can restore the immune response in adult carrier mice, facilitated by the activation and development of the intestinal blood vessel system and the immune system.
Background: The intestinal microbiota fundamentally guides the development of a normal intestinal physiology, the education, and functioning of the mucosal immune system. The Citrobacter rodentium-carrier model in germ-free (GF) mice is suitable to study the influence of selected microbes on an otherwise blunted immune response in the absence of intestinal commensals. Results: Here, we describe that colonization of adult carrier mice with 14 selected commensal microbes (OMM12 + MC2) was sufficient to reestablish the host immune response to enteric pathogens; this conversion was facilitated by maturation and activation of the intestinal blood vessel system and the step- and timewise stimulation of innate and adaptive immunity. While the immature colon of C. rodentium-infected GF mice did not allow sufficient extravasation of neutrophils into the gut lumen, colonization with OMM12 + MC2 commensals initiated the expansion and activation of the visceral vascular system enabling granulocyte transmigration into the gut lumen for effective pathogen elimination. Conclusions: Consortium modeling revealed that the addition of two facultative anaerobes to the OMM12 community was essential to further progress the intestinal development. Moreover, this study demonstrates the therapeutic value of a defined consortium to promote intestinal maturation and immunity even in adult organisms.

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