Researchers at the UC Davis School of Medicine announced on July 30 that they have identified a naturally occurring metabolite, 10-hydroxystearic acid (10-HSA), which repairs gut damage caused by HIV infection and improves the effectiveness of antiretroviral therapy in a nonhuman primate model of HIV/AIDS.
The biotherapeutic metabolite 10-HSA is produced by the beneficial gut bacterium Lactiplantibacillus plantarum. This bacterium is commonly found in over-the-counter probiotics, fermented foods, and occurs naturally in the human gut. The findings were published in Nature Microbiology.
HIV targets gut-associated lymphoid tissue early during infection, damaging immune and epithelial cells in the intestinal lining. This leads to inflammation, a leaky gut barrier, weakened defense systems, decreased nutrient absorption, and disrupted mitochondrial function. Even with strict adherence to antiretroviral therapy (ART), many people living with HIV experience persistent gut inflammation.
In this study, researchers used X-ray crystallography to show that 10-HSA binds directly to PPAR-alpha—a nuclear receptor regulating key biological processes—promoting histone crotonylation and reprogramming gene expression to restore mitochondrial function and energy metabolism while supporting repair of the gut lining. The team also found that 10-HSA increased mitochondrial respiration of epithelial cells under inflammatory conditions associated with HIV.
To test whether these benefits translate beyond laboratory models, two independent studies were conducted at the UC Davis National Biomedical Research Institute using non-human primates infected with simian immunodeficiency virus (SIV). "The findings suggest repairing the tissue damage caused by HIV may be as important as suppressing the virus itself with antiretroviral therapy," said Dylan Kramer, first author of the study and recent Ph.D. graduate from the Dandekar Lab. "By rebuilding the gut barrier, restoring mitochondrial function and reducing inflammation, 10-HSA helps create conditions that support stronger immune recovery and more effective antiviral therapy for HIV." The authors noted there were no adverse effects observed during preclinical studies, but cautioned that further research is needed before testing safety and effectiveness in humans.
"Our research shows that host health, microbial health and viral control are deeply interconnected," Dandekar said. She added: "The restoration of gut barrier integrity and microbial balance through 10-HSA supplementation may represent a promising therapeutic strategy, with implications that extend beyond HIV to other chronic inflammatory diseases of the gastrointestinal tract."
