The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.

Christensenella minuta Alleviates Acetaminophen-Induced Hepatotoxicity by Regulating Phenylalanine Metabolism.

Acetaminophen (APAP)-induced liver injury (AILI), even liver failure, is a significant challenge due to the limited availability of therapeutic medicine. Christensenella minuta (C. minuta), as a probiotic therapy, has shown promising prospects in metabolism and inflammatory diseases. Our research aimed to examine the influence of C. minuta on AILI and explore the molecular pathways underlying it. We found that administration of C. minuta remarkably alleviated AILI in a mouse model, as evidenced by decreased levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and improvements in the histopathological features of liver sections. Additionally, there was a notable decrease in malondialdehyde (MDA), accompanied by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and superoxide dismutase (SOD) activity. Furthermore, there was a significant reduction in inflammatory markers (IL6, IL1ß, TNF-α). C. minuta regulated phenylalanine metabolism. No significant difference in intestinal permeability was observed in either the model group or the treatment group. High levels of phenylalanine aggravated liver damage, which may be linked to phenylalanine-induced dysbiosis and dysregulation in cytochrome P450 metabolism, sphingolipid metabolism, the PI3K-AKT pathway, and the Integrin pathway. Furthermore, C. minuta restored the diversity of the microbiota, modulated metabolic pathways and MAPK pathway. Overall, this research demonstrates that supplementing with C. minuta offers both preventive and remedial benefits against AILI by modulating the gut microbiota, phenylalanine metabolism, oxidative stress, and the MAPK pathway, with high phenylalanine supplementation being identified as a risk factor exacerbating liver injury.

Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice.

INTRODUCTION: Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear. OBJECTIVES: In this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice. METHODS: The mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed. RESULTS: Sedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2. CONCLUSION: Sedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.

Protective effect of Pediococcus pentosaceus Li05 on diarrhea-predominant irritable bowel syndrome in rats.

Pediococcus pentosaceus Li05 (Li05) has demonstrated potential benefits in various intestinal and liver diseases, but its potential and mechanisms in relieving diarrhea have not been understood. The objective of this research was to examine the effects and mechanisms of Li05 in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) induced by wrap restrain stress (WRS) and 4% acetic acid. The results demonstrated that Li05 effectively alleviated weight loss, visceral sensitivity and diarrhea in rats with IBS-D. It also improved intestinal and systemic inflammation by reducing the levels of chemokines and proinflammatory cytokines (GRO/KC, RANTES, IL-1ß, IL-7, and IL-18). The 5-hydroxytryptamine (5-HT) signaling pathway is involved in regulating excessive intestinal motility and secretion in IBS-D. Li05 effectively reduced the expression levels of the 5-HT3B receptor (5-HT3BR) (p < 0.01) in the intestine. Additionally, Li05 intervention had a regulatory effect on the gut composition, with a decrease in the abundance of [Ruminococcus] gauvreauii group, Dubosiella, Erysipelatoclostridium and Blautia, and an increase in the abundance of Alloprevotella, Anaerotruncus and Mucispirillum. Furthermore, Li05 induced significant changes in fatty acid and amino acid metabolism in the gut of rats with IBS-D. These findings indicate that Li05 exhibits an effective improvement in IBS-D symptoms by reducing inflammation and modulating gut microbiota and metabolism. Based on the above results, Li05 holds promise as a potential probiotic for managing IBS-D.

ANKRD22 is a novel therapeutic target for gastric mucosal injury.

Ankyrin repeat domain 22 (ANKRD22) is a nuclear-encoded mitochondrial membrane protein that is highly expressed in normal gastric mucosal epithelial cells and activated macrophages. As a regulator of mitochondrial Ca2+, ANKRD22 could help repair damaged gastric mucosa by promoting the mobilization of LGR5+ gastric epithelial cells via the upregulation of Wnt/ß-catenin pathway activity in a mouse model. Furthermore, the inhibition of ANKRD22 alleviated the macrophage activation-mediated inflammatory response by reducing the phosphorylation of nuclear factor of activated T cells (NFAT). ANKRD22 plays a significant role in the repair of gastric mucosal damage and may become an ideal novel target for the treatment of gastric mucosal injury. However, there is no systematic introduction to ANKRD22 targeting. Therefore, we wrote this review to elaborate the functional mechanism of ANKRD22 in gastric mucosal injury and to analyze its potential application value in clinical therapy.