Bifidobacterium pseudolongum contributes to the intestinal barrier dysfunction in mice.
The intestinal barrier consists of mucosal, epithelial, and immunological barriers and serves as a dynamic interface between the host and its environment. Disruption of the intestinal barrier integrity is a leading cause of various gastrointestinal diseases, such as inflammatory bowel disease. The homeostasis of the intestinal barrier is tightly regulated by crosstalk between gut microbes and the immune system; however, the implication of the immune system on the imbalance of gut microbes that disrupts barrier integrity remains to be fully elucidated.  An inhibitory immunoglobulin-like receptor, Allergin-1, is expressed on mast cells and dendritic cells and inhibits Toll-like receptor (TLR)-2 and TLR-4 signaling in these cells. Since TLRs are major sensors of microbiota and are involved in local epithelial homeostasis, we investigated the role of Allergin-1 in maintaining intestinal homeostasis. Allergin-1-deficient (Milr1 -/-) mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis than did wild-type (WT) mice. Milr1 -/- mice showed an enhanced intestinal permeability than did WT mice even before DSS administration. Treatment of Milr1 -/- mice with neomycin, but not ampicillin, restored intestinal permeability. The 16S rRNA gene sequencing analysis demonstrated that Bifidobacterium (B) pseudolongum was the dominant bacteria in Milr1 -/- mice after treatment with ampicillin. Although the transfer of B. pseudolongum to the germ-free WT mice had no effect on intestinal permeability, its transfer into ampicillin-treated WT mice enhanced intestinal permeability. These results demonstrated that Allergin-1 is involved in intestinal dysbiosis of B. pseudolongum, which contributes to intestinal barrier dysfunction in collaboration with neomycin-sensitive and ampicillin-resistant microbiota.