Multiomics Analysis Reveals Gut Virome-Bacteria-Metabolite Interactions and Their Associations with Symptoms in Patients with IBS-D.

The gut microbiota is involved in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), but few studies have focused on the role of the gut virome in IBS-D. We aimed to explore the characteristics of the gut virome in patients with IBS-D, its interactions with bacteria and metabolites, and the associations between gut multiomics profiles and symptoms. This study enrolled twelve patients with IBS-D and eight healthy controls (HCs). The stool samples were subjected to metavirome sequencing, 16S rRNA gene sequencing, and untargeted metabolomic analysis. The participants completed relevant scales to assess the severity of their gastrointestinal symptoms, depression, and anxiety. The results revealed unique DNA and RNA virome profiles in patients with IBS-D with significant alterations in the abundance of contigs from Siphoviridae, Podoviridae, Microviridae, Picobirnaviridae, and Tombusviridae. Single-omics co-occurrence network analyses demonstrated distinct differences in the gut virus, bacteria, and metabolite network patterns between patients with IBS-D and HCs. Multiomics networks revealed that short-chain fatty acid-producing bacteria occupied more core positions in IBS-D networks, but had fewer links to viruses. Amino acids and their derivatives exhibit unique connectivity patterns and centrality features within the IBS-D network. The gastrointestinal and psychological symptom factors of patients with IBS-D were highly clustered in the symptom-multiomics network compared with those of HCs. Machine learning models based on multiomics data can distinguish IBS-D patients from HCs and predict the scores of gastrointestinal and psychological symptoms. This study provides insights into the interactions among gut viruses, bacteria, metabolites, and clinical symptoms in patients with IBS-D, indicating further classification and personalized treatment for IBS-D.

Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites.

Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.

Outcome-Specific Efficacy of Different Probiotic Strains and Mixtures in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.

Intestinal crosstalk between bile acids and microbiota in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a relatively common functional gastrointestinal disease with a disturbance of intestinal bacteria. Bile acids, gut microbiota, and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Recent studies suggested that the bile acid-gut microbiota axis played a key role in the development of IBS patients. In order to investigate the role of bile acids in the pathogenesis of IBS and present potentially relevant clinical implications, we conducted a literature search on intestinal interactions between bile acid and gut microbiota. The intestinal crosstalk between bile acids and gut microbiota shapes the compositional and functional alterations in IBS, manifesting as gut microbial dysbiosis, disturbed bile acid pathway, and alteration of the microbial metabolites. Collaboratively, bile acid conducts the pathogenesis of IBS through the alterations of the farnesoid-X receptor and G protein-coupled receptor. Diagnostic markers and treatments targeting the bile acids and its receptor showed promising potential in the management of IBS. Bile acids and gut microbiota play a key role in the development of IBS and make attractive biomarkers for treatments. Individualized therapy aiming at bile acids and its receptor may provide significant diagnostic and requires further investigation.

Feasibility and Safety of Transgastric Natural Orifice Transluminal Endoscopic Surgery in the Diagnosis of Ascites of Unknown Origin.

Objective: The purpose of this study was to evaluate the feasibility and safety of transgastric natural orifice transluminal endoscopic surgery (TG-NOTES) combined with biopsy in the diagnosis of unknown ascites. Method: This retrospective study used data from the first affiliated hospital of Nanchang university on 51 patients who were diagnosed with ascites of unknown origin between January 2013 and May 2019 and experienced peritoneal biopsy through TG-NOTES. The outcome measures included diagnostic accuracy and procedure-related adverse events. Results: TG-NOTES was performed successfully in 46 of 51 patients, tuberculous ascites in 38 cases, carcinomatous ascites in 4 cases, cirrhotic ascites in 1 case, and 3 cases showed no obvious abnormalities in pathological result. Five cases failed to be diagnosed because of abdominal adhesions. The diagnostic rate of TG-NOTES was 84.3%. There were no severe procedure-related adverse events and no mortality. All patients had good wound healing and no complaint of discomfort on follow-up. Conclusion: The majority of ascites of unknown origin can be expounded through TG-NOTES combined with biopsy without severe complication, therefore, it is a feasible and safe method to detect the cause of unexplained ascites.

Efficacy of different endoscopic treatments in patients with gastroesophageal reflux disease: a systematic review and network meta-analysis.

BACKGROUND: Both transoral incisionless fundoplication (TIF) and radiofrequency ablation (Stretta) are representative endoscopic treatments for gastroesophageal reflux disease (GERD), but they have not been directly compared. This systematic review and network meta-analysis (NMA) evaluated the comparative effects of Stretta, TIF, and proton pump inhibitors (PPIs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Embase were searched for randomized controlled trials (RCTs) that compared the efficacy of either the Stretta, TIF, or PPIs/sham procedure for GERD treatment. The NMA was conducted using frequentist methods. RESULTS: A total of 516 participants from 10 RCTs were included in this NMA. Both Stretta (mean difference, MD - 9.77, 95% confidence interval, CI - 12.85 to - 6.70) and TIF (MD - 12.22, 95% CI - 15.93 to - 8.52) were significantly superior to PPIs at improving health-related quality of life (HRQL) scores and heartburn scores (Stretta: MD - 1.53, 95% CI - 2.98 to - 0.08; TIF: MD - 9.60, 95% CI - 17.79 to - 1.41). Stretta (MD - 3.77, 95% CI - 6.88 to - 0.65) was less effective at increasing lower esophageal sphincter (LES) pressure than TIF. Stretta was significantly superior to TIF (MD - 3.25, 95% CI - 5.95 to - 0.56) at improving esophageal acid exposure. Regarding the decrease in PPIs utility and esophagitis incidence, no significant differences were found between TIF and Stretta. CONCLUSION: In terms of short-term reduction of the HRQL score and heartburn score in patients with GERD, TIF and Stretta may be comparable to each other, and both may be more effective than PPIs. TIF may increase the LES pressure in comparison with Stretta and PPIs. PPIs may reduce the percentage of time pH < 4.0 when compared with TIF. This evidence should be interpreted with caution given the small number of included studies and inherent heterogeneity. Registration No. CRD42020188345.