Selected commensals educate the intestinal vascular and immune system for immunocompetence

Abstract

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.

Lymphodepletion – an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle

“…In addition to the LD regimen itself, antibiotic treatment as prophylactic intervention does cause dysbiotic states. Experimental approaches have shown that the microbial composition and commensalderived metabolites crucially impact on host immunity, thereby shaping either tolerogenic or activating environments (88,89). Further, recent studies have shown that the microbiome is capable of influencing the functionality of CD19-specific CAR-T cells in patients.…”

Gut Microbiota and the Microvasculature

“…Experimentation with germ-free mouse models demonstrated that this arrested angiogenic program is rapidly restarted by colonization with a gut microbiota or the abundant polysaccharide-degrading, Gram-negative bacterium Bacteroides thetaiotaomicron (Stappenbeck et al 2002). Furthermore, the minimal microbial consortium oligo-mouse microbiota (OMM 12 ), a community of 12 mouse intestinal bacteria, was demonstrated to enhance the maturation of small intestinal villus capillaries (Garzetti et al 2017;Romero et al 2022).…”

Impact of gut-peripheral nervous system axis on the development of diabetic neuropathy

“… 47 , 48 Gut microbiota has various physiological functions in the host, including strengthening epithelial-intestinal barrier integrity, 49 maintenance of energy homeostasis, 50 protection against pathogens, 51 and regulation of host immunity. 52 …”