BACKGROUNDConstipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids (SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin, lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking.AIMTo assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation.METHODSAdults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined. The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated.RESULTSThere were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement. However, after prebiotic usage, serum cluster of differentiation (CD) 14 and lipopolysaccharide (LPS) concentrations were significantly decreased (CD14, P = 0.012; LPS, P < 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group (P < 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group (P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae (phylum Firmicutes, class Clostridia) (P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs (P < 0.05).CONCLUSIONAlterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.

Obesity-induced chronic inflammation is known to increase the risk of ulcerative colitis, Crohn’s disease, and colorectal cancer. Accumulating evidence suggests that leptin and insulin are key molecules linking obesity with diseases of the lower intestine. Here, we identified serum phenotype-associated genes in the colon of diet-induced obese mice as early biomarkers of obesity-associated colonic diseases. C57BL/6J mice were fed with either normal diet (ND, 15% of fat calories) or high-fat diet (HFD, 45% of fat calories) for 8 weeks. Serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), leptin, and adiponectin were measured as obesity-related phenotypic markers. Genome-wide gene expression profiles of colon tissue were determined, followed by statistical analyses to detect differentially expressed and serum phenotype-associated genes. HFD-fed mice showed higher serum concentrations of leptin (P < 0.001) and insulin (P < 0.01) than those in the ND group, whereas serum IGF-1 and adiponectin concentrations did not differ between the two dietary groups. Among differentially expressed genes affected by HFD, 135, 128, 110, and 341 genes were associated with serum levels of leptin, insulin, IGF-1, and adiponectin, respectively. We identified 17 leptin-associated genes and 4 insulin-associated genes that inversely responded to HFD and ND. Among these, leptin-associated Peli3 (Pellino E3 ubiquitin protein ligase family member 3), Creb1 (cAMP responsive element binding protein 1), and Enpp2 (ectonucleotide pyrophosphatase/phosphodiesterase 2, autotaxin) and insulin-associated Centg1 (AGAP2, ArfGAP with GTPase domain) are reported to play a role either in obesity or colonic diseases. mRNA expression of these genes was validated by RT-qPCR. Our data suggest Peli3, Creb1, Enpp2, and Centg1 as potential early biomarker candidates for obesity-induced pathophysiological changes in the colon. Future studies verifying the function of these candidates are needed for the prevention, early detection, and treatment of colon diseases.