Background: A low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet has been reported to be associated with improving the symptoms of irritable bowel syndrome (IBS); however, its efficacy as evaluated by different studies remains controversial.Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to explore the efficacy of a low-FODMAP diet (LFD) in alleviating the symptoms of IBS.Methods: A search of the literature for RCTs that assessed the efficacy of an LFD in treating IBS patients was conducted using the electronic databases PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. The searches in each database were conducted from the inception of the database to February 2021. Two independent reviewers screened citations and a third reviewer resolved disagreements. Two independent reviewers also performed eligibility assessments and data extraction. The RCTs that evaluated LFDs vs. a normal IBS or usual diet and assessed changes of IBS symptoms were included in the search. Data were synthesized as the relative risk of global symptoms improvement, mean difference of IBS Severity Scoring System (IBS-SSS) score, sub-items of IBS-SSS irritable bowel syndrome-related quality of life (IBS-QOL), hospital anxiety and depression scale (HADS), stool consistency/frequency, and body mass index (BMI) using a random effects model. The risk of bias was assessed using Risk of Bias Tool 2 (RoB 2). The bias of publication was assessed based on Egger's regression analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Results: A total of 2,768 citations were identified. After full-text screening, a total of 10 studies were eligible for the systematic review and were subsequently used to compare an LFD with various control interventions in 511 participants. An LFD was associated with the improvement of global symptoms [n = 420; Risk Ratio (RR) = 1.54; 95% Confidence Interval (CI) 1.18 to 2; I² = 38%], improvement of stool consistency [n = 434; Mean difference (MD) = −0.25; 95% CI −0.44 to −0.06; I²= 19%), and a reduction trend of stool frequency (n = 434; MD = −0.28; 95% CI −0.57 to 0.01; I² = 68%) compared with control interventions. There was no statistically significant change in IBS-QOL (n = 484; MD = 2.77; 95% CI −2 to 7.55; I² = 62%), anxiety score (n = 150; MD = −0.45; 95% CI −3.38 to 2.49; I² = 86%), depression score (n = 150; MD = −0.05; 95% CI −2.5 to 2.4; I² = 88%), and BMI (n = 110; MD = −0.22; 95% CI −1.89 to 1.45; I² = 14%). The overall quality of the data was “moderate” for “global improvement of IBS symptom,” “stool consistency,” “stool consistency for IBS with diarrhea (IBS-D),” and “stool frequency for IBS-D,” and “low” or “very low” for other outcomes according to GRADE criteria.Conclusion: An LFD is effective in reducing the global symptoms and improving the bowel habits of adult IBS patients. The efficacy for IBS-D patients can also be more pronounced.Systematic Review Registration: CRD42021235843.

Background and aims: Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown. Methods: HSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16 s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury. Results: MCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury. Conclusions: Gut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.

Background: Little is known about intestinal fungi in IBS patients whose gut bacteria have been investigated a lot. In order to explore causal relationship between IBS and gut mycobiome, and use gut fungi to diagnose or even treat IBS, further characterization of it in IBS is required.Methods: Fifty‐five diarrhea‐predominant IBS (D‐IBS) patients fulfilling Rome III criteria, and 16 healthy controls (HC) were recruited. Fresh fecal samples were collected and used for 16s rRNA and ITS2 high‐throughput sequencing. Diversity and composition of gut bacteria and fungi, as well as bacterial‐fungal interactions in D‐IBS patients, were characterized. Specific fungal taxa differentiating D‐IBS from HC were recognized by LEfSe and RandomForest methods, and their association with clinical symptoms was assessed by Spearman's correlation.Results: Diarrhea‐predominant irritable bowel syndrome patients showed abnormal (IBS‐dysbiosis) or normal (HC‐like IBS) fecal bacterial structure and diversity compared with healthy controls. However, fecal fungal signatures differed absolutely between D‐IBS and HC, which indicated a more susceptible alteration of gut fungi than bacteria in D‐IBS. Fecal fungi showed significant correlations with IBS symptoms, especially Mycosphaerella, Aspergillus, Sporidiobolus, and Pandora which were identified to potentially differentiate D‐IBS from HC. Moreover, compared with HC there were markedly declined bacterial‐fungal interactions in D‐IBS, in which Candida changed from negative to positive correlations with bacteria, and Eurotium changed from positive correlations to irrelevance, while Debaryomyces gained negative correlations with bacteria.Conclusions: Gut fungal dysbiosis and altered bacterial‐fungal interactions were present in patients with D‐IBS, and gut fungi could be used to diagnose D‐IBS.