Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial.

BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.

Competitive Biotransformation Among Phenolic Xenobiotic Mixtures: Underestimated Risks for Toxicity Assessment.

Humans are inevitably exposed to a complex mixture of organic contaminants (i.e., xenobiotics) through diet, environment, and behavior. Biotransformation makes key contributions to the elimination of xenobiotics and greatly mediates the toxicity. However, most biotransformation studies were conducted using individual chemical, and whether coexposure of multiple environmental chemicals will affect each other's fate in the human body is still in its infancy. In this study, bisphenol A (BPA) was selected as a model compound. Its biotransformation was investigated under single exposure/coexposure to other phenolic xenobiotics (triclosan, tetrabromobisphenol A, and bisphenol S) in liver microsome and cell models. The result shows that binary exposures exhibit significant inhibitory effects on the BPA metabolism, especially the sulfate conjugation. In combination of analysis on inhibition models and enzyme activity, the inhibition effect was suggested to be primarily driven by competition for metabolizing enzymes. A mixture with 22 phenolic chemicals was further examined to disrupt BPA at various human-relevant levels. Again, the result demonstrates significant inhibition on the BPA metabolism, indicating the possible natural existence of our finding. Overall, our results show that biotransformation of phenolic xenobiotics can be significantly altered by coexposure, which provides referential evidence on underestimated risks of simultaneous exposure to environmental toxicants.

The occurrence of bisphenol plasticizers in paired dust and urine samples and its association with oxidative stress.

Bisphenol A diglycidy ether (BADGE) and its derivatives are epoxy resins and widely used as emerging plasticizers in food packages and material coating. Though known as endocrine disruptors, little information is available on their occurrence, exposure routes and toxicity. Besides, the analysis of BADGE and its derivatives has always been a challenge due to their reactive chemical properties and the background contamination. Therefore, we firstly developed a novel water-free method to analyze BADGE and its derivatives in dust samples together with other two typical plasticizers bisphenol A (BPA) and bisphenol S (BPS). In order to investigate the levels in paired dust and urine samples, 33 paired samples were collected from Singapore. In both dust and urine samples, the predominant compounds were BPA, BADGE-2H2O and BPS. A significantly positive correlation of BPA levels in paired dust and urine samples was observed in this small-scale study. To tentatively explore the human health effect from exposure to these bisphenol plasticizers, we assessed the correlation between the urinary concentrations of these compounds and oxo-2'-deoxyguanosine (8-OHdG), an oxidative stress biomarker. The result showed that 8-OHdG levels in urine samples was positively correlated with urinary BPA level and body mass index (BMI), suggesting that elevated oxidative stress might be associated with BPA exposure and obesity. In the future, a larger scale study is warranted due to the limited sample size in this study.

"Cocktail" of Xenobiotics at Human Relevant Levels Reshapes the Gut Bacterial Metabolome in a Species-Specific Manner.

The human gut microbiome experiences long-term exposure to numerous organic contaminants (e.g., xenobiotics) in the digestive tract, and the possible consequences have rarely been characterized. To date, very few studies have investigated the metabolic variation from different species of gut bacteria in response to xenobiotic mixtures. In this study, we applied liquid chromatography mass spectrometry-based global metabolomics, coupled with targeted metabolomics, to characterize the model gut bacterial responses toward the xenobiotic mixture, covering diverse classes of compounds at human relevant concentrations. The xenobiotic "cocktail" will not likely affect the growth or morphological properties of model bacteria at human relevant concentrations. However, the metabolic results were distinct between four model bacteria and dose levels, showing species-specific and dose-dependent responsive patterns among different commensal gut bacteria. The key metabolites responsive to xenobiotic exposure are mainly involved in amino acid metabolism and central carbon metabolism, including sulfur-containing amino acids, aromatic amino acids, amino sugars, neurotransmitters, and energy-related metabolic pathways. Many of those metabolites also play an important role in the host's health. In summary, our results show that the gut microbiome can be significantly perturbed by exposure to xenobiotic mixtures at human relevant levels, providing key information on susceptibilities of individuals with diverse gut microbial structures.