Inhibition of GABA(A)R or Application of Lactobacillus casei Zhang Alleviates Ulcerative Colitis in Mice: GABA(A)R as a Potential Target for Intestinal Epithelial Renewal and Repair

Emerging evidence indicates that the gamma−aminobutyric acid type A receptor (GABA(A)R) and Lactobacillus casei Zhang regulate colitis in a variety of ways, such as by participating in host immune and inflammatory responses, altering the gut microbiota, and influencing intestinal barrier function. However, not much is known about the mechanisms by which GABA(A)R and L. casei affect colon epithelial cell renewal and the interaction between GABA(A)R and L. casei during this process. To elucidate this, we established a dextran sulfate sodium (DSS)−induced model and measured the mouse body weights, colon length, the disease activity index (DAI), and histological scores. Our results indicated that inhibition of GABA(A)R alleviated the DSS−induced colitis symptoms, resulting in less weight loss and more intact colon tissue. Moreover, treatment with bicuculline (Bic, a GABA(A)R inhibitor) increased the levels of PCNA, β−catenin, and TCF4 in mice with colitis. Interestingly, open field test performances showed that inhibition of GABA(A)R also attenuated colitis−related anxiety−like behavior. By 16S RNA gene sequencing analysis, we showed that inhibition of GABA(A)R partially reversed the gut dysbacteriosis of DSS−induced mice and increased the abundance of beneficial bacteria. Additionally, L. casei Zhang supplementation inhibited the expression of GABA(A)R in mice with colitis, promoted the proliferation and renewal of colon epithelial cells, and alleviated anxiety−like behavior and intestinal microflora disorder in mice. Thus, GABA(A)R plays a key role in the beneficial effects of L. casei on DSS−induced colitis in mice.