Blueberry intervention mitigates detrimental microbial metabolite trimethylamine N-oxide by modulating gut microbes.

Gut microbes play a pivotal role in host physiology by producing beneficial or detrimental metabolites. Gut bacteria metabolize dietary choline and L-carnitine to trimethylamine (TMA) which is then converted to trimethylamine-N-oxide (TMAO). An elevated circulating TMAO is associated with diabetes, obesity, cardiovascular disease, and cancer in humans. In the present study, we investigated the effect of dietary blueberries and strawberries at a nutritional dosage on TMA/TMAO production and the possible role of gut microbes. Blueberry cohort mice received a control (C) or freeze-dried blueberry supplemented (CB) diet for 12 weeks and subgroups received an antibiotics cocktail (CA and CBA). Strawberry cohort mice received a control (N) or strawberry-supplemented (NS) diet and subgroups received antibiotics (NA and NSA). Metabolic parameters, choline, TMA, and TMAO were assessed in addition to microbial profiling and characterization of berry powders. Blueberry supplementation (equivalent to 1.5 human servings) reduced circulating TMAO in CB versus C mice (~48%) without changing choline or TMA. This effect was not mediated through alterations in metabolic parameters. Dietary strawberries did not reduce choline, TMA, or TMAO. Depleting gut microbes with antibiotics in these cohorts drastically reduced TMA and TMAO to not-quantified levels. Further, dietary blueberries increased the abundance of bacterial taxa that are negatively associated with circulating TMA/TMAO suggesting the role of gut microbes. Our phenolic profiling indicates that this effect could be due to chlorogenic acid and increased phenolic contents in blueberries. Our study provides evidence for considering dietary blueberries to reduce TMAO and prevent TMAO-induced complications.

Cordyceps inhibits ceramide biosynthesis and improves insulin resistance and hepatic steatosis.

Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps. Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila. Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.

Melatonin-induced changes in the bovine vaginal microbiota during maternal nutrient restriction.

Altering the composition of the bovine vaginal microbiota has proved challenging, with recent studies deeming the microbiota dynamic due to few overall changes being found. Therefore, the objectives of this study were to determine whether gestational age, endogenous progesterone, maternal nutrient restriction, or dietary melatonin altered the composition of the bovine vaginal microbiota. Brangus heifers (n = 29) from timed artificial insemination to day 240 of gestation were used; at day 160 of gestation, heifers were assigned to either an adequate (ADQ; n = 14; 100% NRC requirements) or restricted (RES; n = 15; 60% NRC requirements) nutritional plane and were either supplemented with dietary melatonin (MEL; n = 15) or not supplemented (CON; n = 14). Samples for vaginal microbiota analysis were taken on day 0 (prior to artificial insemination), day 150 (prior to dietary treatments), and day 220 of gestation (60 d post-treatment initiation) using a double guarded culture swab. The vaginal bacterial overall community structure was determined through sequencing the V4 region of the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via 2-way ANOVA; ß diversity was compared via PERMANOVA. The linear discriminant analysis for effect size (LEfSe) pipeline was utilized for analysis of taxonomic rank differences between bacterial communities. Gestational age, progesterone concentration, and maternal nutritional plane did not alter α or ß diversity of the vaginal microbiota. However, gestational age resulted in compositional changes at the order, family, and genus level. Moreover, dietary melatonin supplementation did not alter α diversity of the vaginal microbiota but did alter ß diversity (P = 0.02). Specifically, melatonin altered the composition at the genus level and increased the prevalence of aerobic bacteria in the vaginal tract. To date, melatonin is the first hormone associated with altering the composition of the bovine vaginal microbiota.