Dietary delta‐tocotrienol favors abundance and diversity of beneficial microbiomes in obese male mice

Abstract

Obesity and its associated metabolic disorders are a world‐wide health problem. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects. Modulating gut microbiota through bioactive compounds could be a potential therapeutic option. Our previous study has demonstrated that tocotrienols (TT) exert beneficial effects on glucose homeostasis. Therefore, the goal of this study was to further characterize TT‐driven shifts in the cecal microbiome in obese mice with insulin resistance. Twenty male C57BL/6J mice (6‐week‐old) were divided into 2 groups: high‐fat diet (HFD, 60% energy from fat) and HFD+800 mg TT/kg diet (TT800) for 14 weeks. TT is a mixture of 90% delta‐TT and 10% gamma‐TT. To determine the effects of TT on glucose homeostasis and insulin resistance, glucose tolerance and insulin tolerance tests were performed. For microbiome determination, cecal content was collected, DNA was extracted, and 16S rRNA gene metagenome was sequenced. Compared to the HFD group, TT supplementation improved glucose homeostasis as measured by both glucose tolerance test (369.3±22.6 and 243.6±38.9 mg/dL for HFD and TT800, respectively) and insulin tolerance test (relative to time zero: 53.1% and 44.4% for HFD and TT800, respectively). Relative to the HFD diet, dietary TT supplementation increased the Bacteroidetes/Firmicutes ratio in mouse cecum. The number of bacteria which belong to Clostridiales order, especially the Oscillospira genus (Firmicutes phylum) was decreased by 2 fold, whereas the number of S24–7 family members (Bacteroidetes phylum) was significantly increased. Representation of the Akkermansia genus (mucolytic bacteria of Verrucomicrobia phylum) was also increased significantly in the cecal feces of animals supplemented with TT. This study demonstrates that the beneficial effect of TT on glucose homeostasis may be mediated in part through increasing the abundance of beneficial gut microbiome in obese male mice with insulin resistance.Support or Funding InformationAmerican River Nutrition, Inc., Hadley, MA