Researchers report that a drug that appears to target specific intestinal bacteria in the guts of mice may create a chain reaction that could eventually lead to new treatments for obesity and diabetes in humans.
Mice fed a high-fat diet and provided tempol, an antioxidant that may help protect people from the effects of radiation, were significantly less obese than those that did not receive the drug, according to Andrew Patterson, Ph.D., assistant professor of molecular toxicology, Penn State, who worked with Frank J. Gonzalez, Ph.D., laboratory metabolism chief, and James B. Mitchell, Ph.D., radiation biology branch chief, both of the National Cancer Institute.
“The two interesting findings are that the mice that received tempol didn’t gain as much weight and the tempol somehow impacted the gut microbiome [the biological environment of microorganisms within the human body] of these mice,” said Dr. Patterson.
The scientists, who reported their findings (“Microbiome remodeling leads to inhibition of intestinal farnesoid X receptor signaling and decreased obesity”) in the current issue of Nature Communications, said that tempol reduces some members of Lactobacillus in the guts of mice. When the Lactobacillus levels decrease, a bile acid (tauro-beta-muricholic acid) increases. This inhibits farnesoid X receptor (FXR), which regulates the metabolism of bile acids, fats, and glucose in the body, according to the researchers.
“Metagenomics and metabolomics revealed that down-regulation of intestinal FXR by tempol treatment was associated with decreased Lactobacillus species and its bile salt hydroxylase activity,” they wrote in their journal article. “The accumulation of T-β-MCA in the intestine was accompanied by inhibition of FXR.”
Other studies hinted at the relationship between tempol, the gut microbiome, and obesity, but did not focus on why the drug seemed to control weight gain, according to Dr. Patterson.
The researchers said these studies are demonstrating how integrated the 100 trillion microbes that make up the human microbiome are with metabolism and health and how the microbiome may provide more pathways to treating other disorders.
“These studies demonstrate a biochemical link between the microbiome, nuclear receptor signaling, and metabolic disorders, and suggest that inhibition of FXR in intestine could be a target for anti-obesity drugs,” wrote the investigators in the journal article..
They also noted that tempol may help treat type 2 diabetes symptoms. In addition to lower weight gain, the tempol-treated mice on a high-fat diet had lower blood glucose and insulin levels.