The gut microbiome is closely linked to many aspects of human health. The microbes there produce their own compounds, many of which can have an impact on the human body, and scientists are beginning to learn more about how the microbiome can influence different organs, including the brain, lungs, and liver. Scientists have now found a molecule called 10-hydroxystearic acid (10-HSA) that is made by gut microbes known as Lactobacillus. This molecule was shown to repair the gut lining and liver damage, restoring the health of the gut-liver axis in mice that had been exposed to aflotoxin, a toxin that damages the liver. The researchers suggested that this molecule might offer a new therapeutic approach for non-alcoholic fatty liver disease (NAFLD). NAFLD is now estimated to affect over 1 in 4 American adults. The findings have been reported in mBio.
"This is the first time a single microbial molecule has been shown to repair both the liver and gut together," said senior study author Satya Dandekar, a distinguished professor and chair at UC Davis Health.
Bile acids, immune signaling, and lipid metabolism are part of the gut-liver axis. So when one aspect of the axis is disrupted, it affects the others. It may also be possible to harness these connections to treat NAFLD, a growing health problem. NAFLD can lead to inflammation and disrupts metabolism, which can both lead to problems with digestion, and may damage the protective barrier in the gut, noted Dandekar.
In this work, the researchers induced inflammation, liver injury, and gut problems in a mouse model by exposing them to aflatoxin B1 (AFB1). When these mice were also given the therapeutic microbial molecule 10-HSA, major improvements were observed. The integrity of the gut barrier was restored; metabolite levels suggested a return to normal metabolic processes; liver functions including detoxification were improved; and immune signaling in the gut returned to normal.
"We think of these microbial products like precision weapons," Dandekar said. "They are released by bacteria at the site of inflammation and act exactly where they're needed to help repair and heal tissue."
The 10-HSA molecule seems to work by activating PPARα, which is involved in lipid metabolism. In NAFLD and other liver diseases, PPARα signaling is disrupted. The repair of tissue and gut health seems to happen when 10-HSA activates PPARα, without the need for synthetic pharmaceuticals.
More research will be needed to confirm these findings in people with gut problems, but it demonstrates the incredible potential for scientists that can harness the power of the gut microbiome to improve human health.
Sources: University of California Davis, mBio
