Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short-Chain Fatty Acids in Experimental Cirrhosis.

Intestinal permeability to translocation of bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota-derived short-chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild-type and recombination activating gene 1 () mice. Naive T cells and Treg cells were transferred into mice. Intestinal permeability was assessed after lipopolysaccharide (LPS) oral administration, and bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight-junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to () was determined by flow cytometry. SCFAs were measured by gas chromatography-mass spectrometry in colonic content before and after challenge. mice showed significantly increased permeability to LPS and bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to bacterial antigen translocation and restored TJ protein expression in mice. Naive T and Treg replenishment in mice restrained proinflammatory differentiation of intestinal lymphocytes in response to . The main SCFA concentration resulted in significant reduction in mice after administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by was reestablished following naive T and Treg reconstitution in mice. The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria-derived SCFAs foster the value of Tregs in preventing bacterial translocation in cirrhosis.