Probiotic-Derived Metabolite 10-HSA Repairs HIV Gut Damage and Boosts ART Response in Preclinical Model
核心洞察
UC Davis researchers identified 10-hydroxystearic acid (搜索) (10-HSA), a metabolite from Lactiplantibacillus plantarum (搜索), that repairs HIV (搜索)-induced gut damage in a nonhuman primate model.
10-HSA binds PPAR-alpha (搜索) and promotes histone crotonylation, restoring mitochondrial function, epithelial barrier integrity, and reducing inflammation.
In combination with ART, 10-HSA accelerated viral clearance, restored gut immune cells, and reestablished beneficial microbiota compared to ART alone.
Scientists at the UC Davis School of Medicine (搜索) have identified a naturally occurring bacterial metabolite that repairs gut damage caused by HIV (搜索) infection and significantly enhances the effectiveness of antiretroviral therapy (搜索) (ART) in a nonhuman primate model. The findings, published in Nature Microbiology, position the metabolite 10-hydroxystearic acid (搜索) (10-HSA) as a promising candidate for a novel adjunctive treatment strategy.
10-HSA is produced by Lactiplantibacillus plantarum (搜索), a common lactic acid bacterium found in over-the-counter probiotics, fermented foods, and the natural human gut microbiome. The research team, led by Satya Dandekar, distinguished professor in the Department of Medical Microbiology and Immunology at UC Davis Health, demonstrated that this single metabolite can trigger a cascade of cellular repair mechanisms that ART alone cannot achieve.
"Current HIV (搜索) therapies are remarkably effective at controlling viral replication, but they do not fully repair the profound damage HIV causes in the gut," said Dandekar. "Our findings suggest that restoring the gut's structural and immune health can enhance antiretroviral treatment and opens an entirely new avenue for achieving more durable control of HIV."
The Gut as an HIV (搜索) Battleground
Gut-associated lymphoid tissue, the body's largest immune tissue, is an early target of HIV (搜索). The virus severely damages immune and epithelial cells in the gut lining, leading to an inflamed, leaky gut, weakened immune defenses, and decreased nutrient absorption. HIV also disrupts mitochondrial function within gut cells. Even with strict ART adherence, many people living with HIV continue to experience persistent gut inflammation.
Globally, HIV (搜索) remains a major public health challenge. In 2025, an estimated 40.9 million people were living with HIV, approximately 1.2 million acquired new infections, and around 570,000 died from AIDS (搜索)-related illnesses.
Previous research from Dandekar's laboratory had shown that L. plantarum could rapidly heal the chronically inflamed leaky gut associated with HIV (搜索). The current study sought to identify the specific molecular mediators responsible for this effect.
Mechanism of Action: From Metabolite to Epigenetic Reprogramming
Among the hundreds of molecules produced by L. plantarum in the virally inflamed gut environment, 10-HSA emerged as the strongest candidate for repairing the gut barrier and reducing inflammation. Using X-ray crystallography to visualize molecular interactions at the atomic level, the researchers demonstrated that 10-HSA directly binds to PPAR-alpha (搜索), a nuclear receptor that regulates key biological processes.
This binding promoted histone crotonylation, an epigenetic modification that helps regulate gene activity. The resulting cascade reprogrammed 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 gut epithelial cells under HIV (搜索) inflammatory conditions, boosting energy-generating capacity and reducing harmful reactive oxygen species.
Preclinical Validation in the SIV Model
Two independent studies were conducted at the UC Davis National Biomedical Research Institute in nonhuman primates infected with simian immunodeficiency virus (SIV), a close relative of HIV (搜索).
The first study evaluated 10-HSA alone without ART. Results showed intestinal repair, improved key markers of gut function, improved mitochondrial health, reduced inflammatory signaling, and partial restoration of the gut microbiota.
The second study evaluated 10-HSA in combination with ART. The combined treatment demonstrated faster clearance of viral burden than ART alone. The combination also promoted faster recovery of gut immune cells, reduced immune activation, restored epithelial barrier integrity, and reestablished beneficial gut microbiota and microbial diversity.
"The findings suggest repairing the tissue damage caused by HIV (搜索) may be as important as suppressing the virus itself with antiretroviral therapy (搜索)," 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."
Broader Implications and Next Steps
The authors caution that the results are from preclinical models, though the studies showed no adverse effects. The research supports advancing to human clinical trials to evaluate the safety and effectiveness of 10-HSA.
"Our research shows that host health, microbial health and viral control are deeply interconnected," Dandekar said. She noted that treating the damaged gut ecosystem facilitates recovery of the immune system, leading to regained functions lost during HIV (搜索) infection, and that addressing gut damage may improve outcomes beyond what antiviral drugs can achieve alone.
Dandekar further suggested that the therapeutic strategy may have implications beyond HIV (搜索): "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."
The University of California has filed a patent application related to therapeutic treatment strategies involving 10-HSA. The research was supported by funding from the National Institutes of Health and the UC Davis School of Medicine (搜索).