IL-22 andLactobacillus delbrueckiimitigate alcohol-induced exacerbation of DSS-induced colitis

Abstract

Ulcerative colitis (UC) is characterized by cycles of active disease flare and inactive disease remission. During UC remission, IL‐22 is up‐regulated, acting as a hallmark of entrance into UC remission. Recently, we found that in our mouse model of binge alcohol and dextran sodium sulfate (DSS)‐induced colitis, alcohol increases severity of UC pathology. In this study, we assessed not only whether alcohol influenced IL‐22 expression and thereby perpetuates UC, but also whether recombinant IL‐22 (rIL‐22) or treatment with a probiotic could alleviate exacerbated symptoms of UC. Levels of large intestine IL‐22 were significantly decreased ∼6.9‐fold in DSS ethanol compared with DSS vehicle. Examination of lamina propria (LP) cells in the large intestine revealed IL‐22+ γδ T cells in DSS vehicle‐treated mice were significantly increased, while IL‐22+ γδ T cells in DSS ethanol mice were unable to mount this IL‐22 response. We administered rIL‐22 and found it restored weight loss of DSS ethanol‐treated mice. Colonic shortening and increased Enterobacteriaceae were also attenuated. Administration of Lactobacillus delbrueckii attenuated weight loss (p < 0.01), colon length (p < 0.001), mitigated increases in Enterobacteriaceae, increased levels of IL‐22, and increased levels of p‐STAT3 back to that of DSS vehicle group in DSS ethanol mice. In contrast, sole administration of L. delbrueckii supernatant was not sufficient to reduce UC exacerbation following alcohol. Our findings suggest L. delbrueckii contributes to repair mechanisms by increasing levels of IL‐22, resulting in phosphorylation of STAT3, thus attenuating the alcohol‐induced increases in intestinal damage after colitis.

Ethanol Extract of Limonium bicolor Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis by Alleviating Inflammation and Restoring Gut Microbiota Dysbiosis in Mice

“…As one of the most well-known probiotics, g_Lactobacillus protects intestinal barrier function and mucosal immunity by increasing the thickness of the colonic mucosa [36][37][38][39]. In addition, it can alleviate UC by increasing the expression of TLR4/NF-κB, IL-22, and other immune-related genes, restoring intestinal mucosal barrier function, modulating gut microbiota dysbiosis, and inhibiting the growth of pathogenic bacteria [40][41][42].…”

Probiotics for the treatment of ulcerative colitis: a review of experimental research from 2018 to 2022

“…However, L. elbrueckii reduces LPS-induced damage of the intestinal epithelium in piglets and improves mucosal barrier function ( Düz et al, 2020 ). Furthermore, in mice with colitis, L. elbrueckii improved symptoms aggravated by alcohol ( Cannon et al, 2022 ). However, whether this is attributed to the ability of L. elbrueckii to counteract the effects of alcohol or the influence of other actions is uncertain.…”

“…However, whether this is attributed to the ability of L. elbrueckii to counteract the effects of alcohol or the influence of other actions is uncertain. Oral administration of L. elbrueckii can improve intestinal integrity by strengthening the intestinal structure and TJ while increasing antioxidant activity via the TLR-nuclear factor erythroid 2-related factor 2 signaling pathway in piglets ( Cannon et al, 2022 ). L. elbrueckii also improves gut immunity in suckling piglets by activating dendritic cells ( Peng et al, 2022 ).…”