The microenvironment of injured murine gut elicits a local pro-restitutive microbiota

Abstract

The mammalian intestine houses a complex microbial community, which influences normal epithelial growth and development, and is integral to the repair of damaged intestinal mucosa1–3. Restitution of injured mucosa involves the recruitment of immune cells, epithelial migration and proliferation4,5. Although microenvironmental alterations have been described in wound healing6, a role for extrinsic influences, such as members of the microbiota, has not been reported. Here, we show that a distinct subpopulation of the normal mucosal-associated gut microbiota expands and preferentially colonizes sites of damaged murine mucosa in response to local environmental cues. Our results demonstrate that formyl peptide receptor 1 (FPR1) and neutrophilic NADPH oxidase (NOX2) are required for the rapid depletion of microenvironmental oxygen and compensatory responses, resulting in a dramatic enrichment of an anaerobic bacterial consortium. Furthermore, the dominant member of this wound-mucosa-associated microbiota, Akkermansia muciniphila (an anaerobic, mucinophilic gut symbiont7,8), stimulated proliferation and migration of enterocytes adjacent to the colonic wounds in a process involving FPR1 and intestinal epithelial-cell-specific NOX1-dependent redox signalling. These findings thus demonstrate how wound microenvironments induce the rapid emergence of ‘probiont’ species that contribute to enhanced repair of mucosal wounds. Such microorganisms could be exploited as potential therapeutics.

Evaluation of a novel fasting approach using plant polysaccharides per meal in human symbionts

“…No similar gastrointestinal reaction was observed after they resumed normal diets for 7 d. We therefore inferred that fermentation of prebiotics formula facilitated the production of gas in intestinal tract. The 16S rRNA sequencing results showed the increase in probiotics such as Bifidobacterium and Akkermansia after one-week FF [40][41][42][43][44]. The most worthy of attentions were the increase in overall abundance and complexity of microorganisms, and the same increase after resuming normal diet for 7 d, which is represented by species richness and Shannon-Wiener Index.…”

Novel insight into the role of microbiota in colorectal surgery

“…Based on the findings of Alam et al ,36 this graph shows the different changes that occur in the microbiota according to the intestinal injury. It shows the important role of the wound-mucosa-associated microbiota in initiating the early healing cascade by stimulating pro-restitutive signalling and increasing cell migration and proliferation.…”

“…Another recent study by Alam et al 36 elegantly shows that both mechanisms of action may coexist to induce intestinal repair upon injury (box 1). They found that Akkermansia muciniphila administration plays a major role in wound healing by creating a specific environment and local environmental changes.…”

Redox signaling mediated by the gut microbiota

“…In addition, investigations utilizing germ-free mice have established a function for the gut microbiome and metabolic regulation [8]. The gut microbiome has also been shown to positively influence homeostasis of the intestinal mucosa by enhancing barrier function, as well as epithelial cell proliferation and survival [9][10][11][12][13][14][15]. For instance, villi of the small intestine of the germ-free mice have impaired angiogenesis [16] and have slower turnover rates of epithelial cells [17].…”