Ban-Lan-Gen Granule Alleviates Dextran Sulfate Sodium-Induced Chronic Relapsing Colitis in Mice via Regulating Gut Microbiota and Restoring Gut SCFA Derived-GLP-1 Production

Abstract

GLP-1 based therapy represents a new treatment option for inflammatory bowel disease. Ban-Lan-Gen (BLG) granule, a known anti-viral TCM formulation, exhibits potential anti-inflammatory activities in treating various kinds of inflammation. However, its anti-inflammatory effect on colitis and the underlying mechanisms remain unknown. Methods: Dextran sulfate sodium (DSS)-induced chronic relapsing colitis in mice was established. The disease activity index, histological sign of damage, and levels of proinflammatory cytokines were performed to assess the protective effects of BLG. Serum GLP-1 level and colonic Gcg, GPR41 and GRP43 expression, the community compositions of gut microbiota, the levels of SCFAs in the feces and GLP-1 release from primary murine colon epithelial cells were performed to characterize the effects of BLG on gut microbiota and gut SCFA derived-GLP-1 production. Results: BLG treatment significantly alleviated body weight loss, DAI, colon shortening, colon tissue damage, and pro-inflammatory cytokine levels of TNF-α, IL-1β and IL-6 in the colon tissues. Moreover, BLG treatment could observably restore colonic Gcg, GPR41 and GRP43 expression and serum GLP-1 level of colitic mice, as well as correct the alteration of gut microbiota in colitic mice by increasing the abundances of SCFA-producing bacteria, eg, Akkermansia and Prevotellaceae_UCG-001, and decreasing the abundances of bacteria, eg, Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas, and Oscillibacter. Furthermore, BLG treatment could markedly increase the levels of SCFAs in feces of colitic mice. In parallel, ex vivo assay also showed that and the extract of feces from BLG-treatment mice could greatly stimulate the secretion of GLP-1 from primary murine colon epithelial cells. Conclusion: These findings suggest that the anti-colitis effects of BLG are achieved at least partly by regulating gut microbiota and restoring gut SCFA derived-GLP-1 production, and BLG has the potential to be developed as a promising agent for the treatment of chronic relapsing colitis.

Potential benefits of metformin and pioglitazone combination therapy via gut microbiota and metabolites in high-fat diet-fed mice

“…Consistent with previous studies, we found that the abundance of several beneficial microbes increased while conditional pathogens were reduced in the metformin and pioglitazone monotherapy groups. We found that the abundance of the beneficial microbe Akkermansia increased in the metformin monotherapy group, and the abundance of several harmful microbiota decreased, such as Eubacterium_xylanophilum_group and Oscillibacter ( Qin et al, 2012 ; Kong et al, 2019 ; Gurung et al, 2020 ; Peng et al, 2022 ). Akkermansia increased, particularly during metformin treatment, in clinical and experimental studies and functioned as a SCFAs-producing and mucin-degrading bacterium ( Ke et al, 2021 ).…”

“…Akkermansia increased, particularly during metformin treatment, in clinical and experimental studies and functioned as a SCFAs-producing and mucin-degrading bacterium ( Ke et al, 2021 ). Eubacterium_xylanophilum_group was found to have increased abundance in ulcerative colitis mice ( Peng et al, 2022 ). Oscillibacter was found a conditional pathogen positively correlated with obesity- and nutrient-related metabolic pathways in high-sucrose diet-fed mice and inflammatory cytokine levels in ulcerative colitis mice ( Kong et al, 2019 ; Peng et al, 2022 ).…”

“…Eubacterium_xylanophilum_group was found to have increased abundance in ulcerative colitis mice ( Peng et al, 2022 ). Oscillibacter was found a conditional pathogen positively correlated with obesity- and nutrient-related metabolic pathways in high-sucrose diet-fed mice and inflammatory cytokine levels in ulcerative colitis mice ( Kong et al, 2019 ; Peng et al, 2022 ). Similar to the metformin monotherapy group, Oscillibacter was also reduced in the pioglitazone monotherapy group.…”

“…Parasutterella was identified as a core component of the gut microbiota in humans and mice and is associated with various health outcomes in bile acid profiles and cholesterol metabolism ( Ju et al, 2019 ). Conversely, several harmful microbes were reduced, such as Oscillibacter, Eubacterium_xylanophilum_group and Lachnospiraceae _UCG-006 ( Kong et al, 2019 ; Li et al, 2020 ; Duan et al, 2022 ; Peng et al, 2022 ). Therefore, the alterations of these beneficial and harmful microbes indicate significant synergistic effects of combination therapy on gut microbiota modification.…”

Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206 + macrophages IL-10 activation

“… 19 Gavage L. johnsonii increased the B/F ratio (Figure S1M ). The relative abundance of bacteria on the family level showed that L. johnsonii increased the levels of Prevotellaceae 20 and order Clostridia , 21 which were closely related to the secretion of short chain fatty acids (SCFAs), and decreased the levels of Lachnospiraceae, Oscillospiraceae and Erysipelotrichaceae (Figure S1O ). We also determined gavage L. johnsonii could colonize in the colon tissues by qPCR analysis ( Figure 1i ).…”