(PTFS04-03-25) Tocotrienol Supplementation Modulates Gut Microbiome Composition in High-Fat Diet-Induced Obese Mice

Objectives: Obesity is strongly linked to an increased risk of colon cancer, in part due to increased inflammation and oxidative stress within the gastrointestinal tract. Tocotrienols, a form of vitamin E with potent anti-inflammatory and antioxidant properties, have shown promise as potential agents in the prevention of obesity-related colon cancer. This study aimed to assess whether tocotrienols can mitigate obesity-induced alterations in the gut microbiome and colon health.

Methods: Individually housed male C57BL/6 mice were randomized to one of three dietary groups: 1) low-fat diet (LFD), 2) high-fat diet (HFD), or 3) high-fat diet supplemented with a mixture of delta (90%) and gamma (10%) tocotrienols (800 mg/kg diet) for 15 weeks. Fecal samples were collected after a one-week acclimation period to the LFD and at the conclusion of the 15-week intervention, and 16s rRNA sequencing was performed to analyze the gut microbiome. Proximal and medial colon tissue was harvested, and inflammatory and antioxidant markers were assessed by PCR.

Results: Mice on the HFD exhibited significant increases in body weight and adiposity, although tocotrienol supplementation did not affect these measures. HFD consumption altered α- and β-diversity of the gut microbiota, and tocotrienol intake prevented this alteration. Additionally, tocotrienol supplementation decreased the abundance of Clostridium, while increasing the abundance of Roseburia, a bacterium positively associated with insulin sensitivity. Despite these microbiome shifts, neither the high-fat diet nor tocotrienol supplementation altered the mRNA expression of the inflammatory and antioxidant markers investigated.

Conclusions: In conclusion, tocotrienols influenced gut microbiome composition, particularly increasing beneficial bacterial populations. Future studies will determine whether tocotrienols impact inflammatory and antioxidant responses when they are elevated in a model of obesity.

Funding Sources: Georgia State University’s Brains & Behavior Seed Grant