Theabrownin is one of the most bioactive compounds in Pu-erh tea. Our previous study revealed that the hypocholesterolemic effect of theabrownin was mediated by the modulation of bile salt hydrolase (BSH)-enriched gut microbiota and bile acid metabolism. In this study, we demonstrated that theabrownin ameliorated high-fat-diet (HFD)-induced obesity by modifying gut microbiota, especially those with 7α-dehydroxylation on the species level, and these changed microbes were positively correlated with secondary bile acid (BA) metabolism. Thus, altered intestinal BAs resulted in shifting bile acid biosynthesis from the classic to the alternative pathway. This shift changed the BA pool by increasing non-12α-hydroxylated-BAs (non-12OH-BAs) and decreasing 12α-hydroxylated BAs (12OH-BAs), which improved energy metabolism in white and brown adipose tissue. This study showed that theabrownin was a potential therapeutic modality for obesity and other metabolic disorders via gut microbiota-driven bile acid alternative synthesis.

Three of the most lethal cancers in the world are the gastrointestinal cancers—gastric (GC), esophageal (EC) and colorectal cancer (CRC)—which are ranked as third, sixth and fourth in cancer deaths globally. Early detection of these cancers is difficult, and a quest is currently on to find non-invasive screening tests to detect these cancers. The reprogramming of energy metabolism is a hallmark of cancer, notably, an increased dependence on aerobic glycolysis which is often referred to as the Warburg effect. This metabolic change results in a unique metabolic profile that distinguishes cancer cells from normal cells. Serum metabolomics analyses allow one to measure the end products of both host and microbiota metabolism present at the time of sample collection. It is a non-invasive procedure requiring only blood collection which encourages greater patient compliance to have more frequent screenings for cancer. In the following review we will examine some of the most current serum metabolomics studies in order to compare their results and test a hypothesis that different tumors, notably, from EC, GC and CRC, have distinguishing serum metabolite profiles.

Background & Aims: Accurate and noninvasive diagnosis and staging of liver fibrosis is essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients. Methods: We quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from Cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively. Results: The panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in Cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent Cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4 and AST/ALT ratio, with both greater sensitivity and specificity. Conclusion: Our study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression.

Hyocholic acid (HCA) and its derivatives are found in only trace amounts in human blood, but constitute approximately 76 % of the bile acid (BA) pool in the pig, a species known for its exceptional resistance to type 2 diabetes mellitus (T2DM). Here we show that HCA species play a crucial role in maintaining glucose homeostasis and preventing T2DM. We found that in two cohort studies (n=1,213), both obesity and diabetes were associated with lower serum concentrations of HCA species. Serum HCA levels in apparently healthy individuals (n=132) were found to be strong predictors for metabolic health 10 years later. Oral administration of HCA increased serum fasting GLP-1, to a greater extent than metformin, in healthy and diabetic mouse models. HCA upregulated GLP-1 secretion in intestinal enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor, a unique mechanism that is not found in other BA species.