Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover design trial (ChiCTR-TTRCC-13003333) in 37 participants with overweight or obesity, we test whether resistant starch (RS) as a dietary supplement influences obesity-related outcomes. Here, we show that RS supplementation for 8 weeks can help to achieve weight loss (mean −2.8 kg) and improve insulin resistance in individuals with excess body weight. The benefits of RS are associated with changes in gut microbiota composition. Supplementation with Bifidobacterium adolescentis, a species that is markedly associated with the alleviation of obesity in the study participants, protects male mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota alter the bile acid profile, reduce inflammation by restoring the intestinal barrier and inhibit lipid absorption. We demonstrate that RS can facilitate weight loss at least partially through B. adolescentis and that the gut microbiota is essential for the action of RS.

Although adverse environmental exposures are considered a major cause of chronic diseases, current studies provide limited information on real-world chemical exposures and related risks. For this study, we collected serum samples from 5696 healthy people and patients, including those with 12 chronic diseases, in China and completed serum biomonitoring including 267 chemicals via gas and liquid chromatography-tandem mass spectrometry. Seventy-four highly frequently detected exposures were used for exposure characterization and risk analysis. The results show that region is the most critical factor influencing human exposure levels, followed by age. Organochlorine pesticides and perfluoroalkyl substances are associated with multiple chronic diseases, and some of them exceed safe ranges. Multi-exposure models reveal significant risk effects of exposure on hyperlipidemia, metabolic syndrome and hyperuricemia. Overall, this study provides a comprehensive human serum exposome atlas and disease risk information, which can guide subsequent in-depth cause-and-effect studies between environmental exposures and human health.

Chronic diseases have become main killers affecting the health of human, and environmental pollution is a major health risk factor that cannot be ignored. It has been reported that exogenous chemical residues including pesticides, herbicides, fungicides, veterinary drugs and persistent organic pollutants are associated with chronic diseases. However, the evidence for their relationship is equivocal and the underlying mechanisms are unclear. We aim to investigate the linkages between serum exogenous chemical residues and 5 main chronic diseases including obesity, hyperuricemia, hypertension, diabetes and dyslipidemia, and further reveal the metabolic perturbations of chronic diseases related to exogenous chemical residue exposure, then gain potential mechanism insight at the metabolic level. LC-MS-based targeted and nontargeted methods were respectively performed to quantify exogenous chemical residues and acquire metabolic profiling of 496 serum samples from chronic disease patients. Non-parametric test, correlation and regression analyses were carried out to investigate the association between exogenous chemical residues and chronic diseases. Metabolome-wide association study combined with the meeting-in-the-middle strategy and mediation analysis was performed to reveal and explain exposure-related metabolic disturbances and their risk to chronic diseases. In the association analysis of 106 serum exogenous chemical residues and 5 chronic diseases, positive associations of serum perfluoroalkyl substances (PFASs) with hyperuricemia were discovered while other associations were not significant. 240 exposure markers of PFASs and 84 disease markers of hyperuricemia were found, and 47 of them were overlapped and considered as putative effective markers. Serum uric acid, amino acids, cholesterol, carnitines, fatty acids, glycerides, glycerophospholipids, ceramides, and a part of sphingolipids were positively correlated with PFASs and associated with increased risk for hyperuricemia. Creatine, creatinine, glyceryl monooleate, phosphatidylcholine 36:6, phosphatidylethanolamine 40:6, cholesterol and sphingolipid 36:1;2O were significant markers which mediated the associations of the residues with hyperuricemia. Our study demonstrated a significantly positive association between PFASs exposure and hyperuricemia. The most significant metabolic abnormality was lipid metabolism which not only was positively associated with PFASs, but also increased the risk of hyperuricemia.