Altered profiles of fecal bile acids correlate with gut microbiota and inflammatory responses in patients with ulcerative colitis

Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.

Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome

Alteration of fecal tryptophan metabolism correlates with shifted microbiota and may be involved in pathogenesis of colorectal cancer

Objective: Cardiometabolic index (CMI) is a well promising indicator for predicting obesity-related diseases, but its predictive value for metabolic associated fatty liver disease (MAFLD) is unclear. This study aimed to investigate the relationship between CMI and MAFLD and to evaluate the predictive value of CMI for MAFLD.Methods: A total of 943 subjects were enrolled in this cross-sectional study. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariate logistic regression analysis was used to systematically evaluate the relationship between CMI and MAFLD. Receiver operating characteristic (ROC) curves were used to assess the predictive power of CMI for MAFLD and to determine the optimal cutoff value. The diagnostic performance of high CMI for MAFLD was validated in 131 subjects with magnetic resonance imaging diagnosis.Results: Subjects with higher CMI exhibited a significantly increased risk of MAFLD. The odds ratio for a 1-standard-deviation increase in CMI was 3.180 (2.102-4.809) after adjusting for various confounding factors. Further subgroup analysis showed that there were significant additive interactions between CMI and MAFLD risk in gender, age, and BMI (P for interaction < 0.05), and the area under the ROC curve(AUC) of CMI for predicting MAFLD were significantly higher in female, young, and nonobese subgroups than that in male, middle-aged and elderly, and obese subgroups (all P < 0.05). Moreover, among nonobese subjects, the AUC of CMI was significantly higher than that of waist circumference, BMI, TG/HDL-C, and TG (all P < 0.05). The best cutoff values of CMI to diagnose MAFLD in males and females were 0.6085 and 0.4319, respectively, and the accuracy, sensitivity, and specificity of high CMI for diagnosing MAFLD in the validation set were 85.5%, 87.5%, and 80%, respectively.Conclusions: CMI was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD. High CMI had excellent diagnostic performance for MALFD, which can enable important clinical value for early identification and screening of MAFLD.

To measure the leptin levels in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and analyze the relationship of leptin with clinical features, visceral sensitivity, mast cells, and nerve fibers. Forty-two patients with IBS-D fulfilling the Rome III criteria and 20 age- and sex-matched healthy controls underwent clinical and psychological evaluations using validated questionnaires (including IBS Symptom Severity Scale, IBS-specific Quality of Life, Hamilton Anxiety Scale, and Hamilton Depression Scale), along with colonoscopy, colonic mucosal biopsy, and visceral sensitivity testing. Serum leptin levels were assayed using enzyme-linked immunosorbent assay. Mucosal leptin expression and localization were evaluated using immunohistochemistry and immunofluorescence. Mucosal leptin mRNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction. Mast cell counts and activation rates were investigated by toluidine blue staining. Correlation analyses between these parameters were performed. There were no statistically significant differences in age, gender, or body mass index between the IBS-D group and the control group. The median IBS Symptom Severity Scale score in the IBS-D group was 225.0 (range, 100-475). IBS-D patients had significantly increased anxiety [IBS-D: median, 6.5; interquartile range (IQR), 3.3; control: median, 2.0; IQR, 2.0; P < 0.001] and depression (IBS-D: median, 7.0; IQR, 3.0; control: median, 3.0; IQR, 2.0; P < 0.001) scores. IBS-D patients had significantly lower first sensation threshold (IBS-D: median, 50.6; IQR, 25.9; control: median, 80.5; IQR, 18.6; P < 0.001), defecation sensation threshold (IBS-D: median, 91.5; IQR, 29.3; control: median, 155.0; IQR, 21.1; P < 0.001) and maximum tolerable threshold (IBS-D: median, 163.2; IQR, 71.2; control: median, 226.2; IQR, 39.3; P < 0.001). Mucosal leptin expression, as reflected by integrated optical density (IBS-D: median, 4424.71; IQR, 4533.63; control: median, 933.65; IQR, 888.10; P < 0.001), leptin mRNA expression (IBS-D: median, 1.1226; IQR, 1.6351; control: median, 0.8947; IQR, 0.4595; P = 0.009), and mast cell activation rate (IBS-D: median, 71.2%; IQR, 12.9%; control group: median, 59.4%; IQR, 18.88%; P < 0.001) were significantly increased in IBS-D patients. The colocalization of leptin and leptin receptors was observed on mast cells and PGP9.5-positive nerve fibers in the intestinal mucosa. Also, leptin expression was positively correlated with anxiety, depression, and the mast cell activation rate, but negatively correlated with the defecation sensation threshold and the maximum tolerance threshold during visceral sensitivity testing (adjusted P < 0.0038). Increased levels of mucosal leptin may interact with mast cells and the nervous system to contribute to the pathogenesis of IBS-D.