The global incidence of inflammatory bowel disease (IBD) continues to rise, yet its precise pathogenesis remains incompletely understood. In recent years, various gut microbiota-derived metabolites have been implicated in the development of IBD. Among them, succinic acid is a key metabolite produced by intestinal flora and serves as a central intermediate in the tricarboxylic acid (TCA) cycle, which plays a pivotal role in the IBD pathogenesis by modulating the intestinal mucosal barrier function, immune-metabolic reprogramming and cellular energy homeostasis. Abnormal succinate metabolism has also been linked to a range of metabolic disorders, including hepatitis, arthritis, diabetes mellitus, and cardiovascular diseases. Recently, its role in IBD has attracted growing interest. This review systematically elucidates the mechanisms by which succinate promotes pro-inflammatory immune phenotypes through a multifaceted network involving macrophage polarization, T-cell metabolic reprogramming, and epithelial-immune cell interactions, largely mediated via the SUCNR1 signaling axis. Furthermore, we explore the therapeutic potential of targeting succinate metabolism, offering new insights into IBD prevention and treatment.

Background: The interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis.Methods: Two-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran’s Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs.Results: We identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora.Conclusion: The present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.

Yiyi Fuzi Baijiang Decoction (YFBD), an ancient prescription developed by the ancient Chinese physician, Zhang Zhongjing, has shown remarkable effects in treating ulcerative colitis (UC). However, there are few studies on its mechanism. This study was designed to explore the potential mechanism of YFBD in treating UC. The principal ingredients of YFBD were analyzed using high-performance liquid chromatography (HPLC). Dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated RAW264.7 cells were used in the study. The body weight and disease activity index (DAI) of mice were recorded and analyzed for 10 days. After sacrifice, the colonic tissues were harvested. The colon length was measured, and the histopathological changes were observed by hematoxylin and eosin staining. The levels of inflammatory cytokines in mice colons and RAW246.7 cells were determined by real-time quantitative PCR and immunofluorescence. The effects of YFBD on the TLR4-mediated PI3K/Akt and NF-κB pathways were determined by western blot analysis. HPLC identified five compounds in YFBD: chlorogenic acid, caffeic acid, benzoylmesaconine, benzoyl aconitine, and quercetin. YFBD alleviated weight loss, colon shortening, and colonic histopathological lesion in mice. Meanwhile, it decreased the DAI and histological score of mice with UC. In addition, YFBD remarkably decreased the levels of interleukin- (IL-) 6, IL-1β, and tumor necrosis factor (TNF)-α in the colons of DSS-induced mice and LPS-stimulated RAW246.7 cells. Furthermore, the expression of key proteins in TLR4-mediated PI3K/Akt and NF-κB pathways significantly decreased with YFBD treatment. In conclusion, YFBD had protective effects on mice with UC, which was in part related to its anti-inflammatory effects and downregulation of TLR4-mediated PI3K/Akt and NF-κB pathways.

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.

Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNB...