Dataset Information

New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-κB signaling pathway

ABSTRACT:

Aim of the study

We aimed to elucidate the synergistic effect and potential mechanism of New Baitouweng Decoction (NBD) combined with fecal microbiota transplantation (FMT) in rats with DSS-induced ulcerative colitis (UC).

Materials and methods

Colitis was induced by 5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. NBD or NBD combined with FMT were administered to the colitis rats. Body weight and disease activity index were measured, and the colon histological change was imaged to further examine the efficacy of NBD and FMT. The specific effects of NBD on STAT3/NF-κB signaling pathway and gut microbiota in rats with UC were also investigated.

Results

The efficacy of NBD in combination with FMT was demonstrated by the lower disease activity index scores; increased tight junction proteins expression; and a lower expression of macrophage marker (F4/80) in colon tissues. NBD combined with FMT elevated the concentrations of short-chain fatty acids and inhibited activation of the JAK2/STAT3/NF-κB related proteins. Furthermore, 16SrDNA sequencing indicated that the gut microbiota in rats with UC was perturbed, in contrast to that in healthy rats. After treatment with NBD and FMT, the diversity and abundance of intestinal flora showed clear improvements. Spearman correlation analysis indicated a strong correlation between specific microbiota and fecal concentrations of acetate, propionate and butyrate.

Conclusions

The protective mechanism of NBD combined with FMT may be linked to regulation NF-κB/STAT3 and restoration of the intestinal flora.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12906-022-03766-z.

SUBMITTER: Gu X

PROVIDER: S-EPMC9686021 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

Project description:Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.