Differential Induction of Antimicrobial REGIII by the Intestinal Microbiota and Bifidobacterium breve NCC2950

Abstract

The intestinal microbiota is a key determinant of gut homeostasis, which is achieved, in part, through regulation of antimicrobial peptide secretion. The aim of this study was to determine the efficiency by which members of the intestinal microbiota induce the antimicrobial peptide REGIII and to elucidate the underlying pathways. We showed that germfree mice have low levels of REGIII-␥ in their ileum and colon compared to mice with different intestinal microbiota backgrounds. Colonization with a microbiota of low diversity (altered Schaedler flora) did not induce the expression of REGIII-␥ as effectively as a complex community (specific pathogen free). Monocolonization with the probiotic Bifidobacterium breve, but not with the nonprobiotic commensal Escherichia coli JM83, upregulated REGIII-␥ expression. Induction of REGIII-␥ by B. breve was abrogated in mice lacking MyD88 and Ticam1 signaling. Both live and heat-inactivated B. breve but not spent culture medium from B. breve induced the expression of REGIII-␣, the human ortholog and homolog of REGIII-␥, in human colonic epithelial cells (Caco-2). Taken together, the results suggest that REGIII-␥ expression in the intestine correlates with the richness of microbiota composition. Also, specific bacteria such as Bifidobacterium breve NCC2950 effectively induce REGIII production in the intestine via the MyD88-Ticam1 pathway. Treatment with this probiotic may enhance the mucosal barrier and protect the host from infection and inflammation.

Lactobacillus rhamnosusCNCM I-3690 and the commensal bacteriumFaecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice

“…5 For instance, the well-known probiotics Escherichia coli Nissle 1917, Lactobacillus rhamnosus GG (LGG) and a mixture of lactobacilli and bifidobacteria prevent the increase in intestinal permeability in vivo. [24][25][26][27] Notably, fermented milk containing Bifidobacterium lactis CNCM I-2494 and LAB strains present in yogurt prevented the increase of intestinal permeability induced by partial restraint stress in rats. 23 Recently, the commensal bacterium Faecalibacterium prausnitzii A2-165, (a major member of the Clostridium leptum group) was shown to display anti-inflammatory and protective effects in both acute 28 and chronic colitis models.…”

Ecobiotherapy Rich in Firmicutes Decreases Susceptibility to Colitis in a Humanized Gnotobiotic Mouse Model

“…Gnotobiotic studies have provided key evidence on how specific bacterial strains influence the development and maturation of host physiology and immunity, including secondary lymphoid development, antimicrobial peptide maturation, and induction of T helper (T H ) cells, such as T regulatory (T REG ) and proinflammatory T H 17 cells. [1][2][3] Components of the intestinal microbiota have differential capacity to influence host responses. 4 For instance, experimentally defined communities, such as the altered Schaedler flora (ASF), Clostridium species, or the polysaccharide A-expressing Bacteroides fragilis predominantly induce T REG in the colon, whereas pathobionts Bilophila wadsworthia and segmented filamentous bacteria are potent inducers of T H 1 and T H 17 cells, respectively.…”

Extrahepatic Diseases and NAFLD: The Triangular Relationship between NAFLD, Type 2-Diabetes and Dysbiosis

“…Paneth cells are part of the epithelium in the small intestine. They produce several antimicrobial peptides for innate immunity such as the regenerating islet-derived III (RegIII-α RegIII-β and RegIII-γ) proteins which belong to the family of C-type lectins [42] . RegIII-γ has a specific antibacterial effect and administration of live Akkermansia muciniphila or Bifidobacterium breve effectively induces REGIII production and specifically the RegIII-γ production protecting the intestine barrier [43] .…”