抑制GABAAR或补充Lactobacillus casei Zhang通过促进肠上皮更新缓解溃疡性结肠炎

Abstract

Emerging evidence indicates that the gamma−aminobutyric acid type A receptor (GABAAR) andLactobacillus caseiZhang 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 GABAAR andL. caseiaffect colon epithelial cell renewal and the interaction between GABAAR andL. caseiduring 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 GABAAR alleviated the DSS−induced colitis symptoms, resulting in less weight loss and more intact colon tissue. Moreover, treatment with bicuculline (Bic, a GABAAR inhibitor) increased the levels of PCNA, β−catenin, and TCF4 in mice with colitis. Interestingly, open field test performances showed that inhibition of GABAAR also attenuated colitis−related anxiety−like behavior. By 16S RNA gene sequencing analysis, we showed that inhibition of GABAAR partially reversed the gut dysbacteriosis of DSS−induced mice and increased the abundance of beneficial bacteria. Additionally,L. caseiZhang supplementation inhibited the expression of GABAAR 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, GABAAR plays a key role in the beneficial effects ofL. caseion DSS−induced colitis in mice.Keywords:ulcerative colitis;GABAAR;Lactobacillus casei;behavior;microbiota