Abstract
Emerging evidence has linked the human metabolic disorder to gut microbiome, which demonstrates enormous capacity for modulating host metabolome, including circulating bile acid (BA) and amino acids levels. Recent studies have also revealed the influences of oral medications on intestinal microbes. However, detailed information on how the gut microbiome and host metabolome change in response to treatment is lacking.
We performed metagenomics and metabolomics analysis in two independent cohorts. We identified increased the abundances of Lactobacillus and Bifidobacterium spp. with depletion of Bacteroides spp., increased plasma unconjugated BAs and the primary/secondary BA ratio on naïve type 2 diabetes (T2D) patients (n=51) with Acarbose treatment, but not Glipizide treatment. Furthermore, compared to patients with a baseline Prevotella enterotype, patients with a baseline Bacteroides enterotype exhibited a more beneficial response to Acarbose treatment improving insulin resistance and plasma BA profiles. In a cohort of lean and obese young Chinese individuals, we identified the abundance of Bacteroides thetaiotaomicron harboring enzymes fermenting glutamate was markedly decreased in obese individuals, and inversely correlated with serum glutamate. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate levels, and alleviated diet-induced body weight gain and adiposity in mice. Furthermore, a decreased abundance of B. thetaiotaomicron and an elevated serum glutamate level have been reversed in obese patients who partially reversed following weight-loss intervention by sleeve gastrectomy.
Our findings show novel interactions between gut microbiota and host metabolome pre-and post-metabolic disorder treatment, pointing to the potential for patient stratification prior to treatment and treatment strategy based on the gut microbiota.