Molecule from gut bacteria repairs liver and gut – and offers hope for fatty liver disease

Scientists from the University of California, Davis, have found a “natural” molecule produced by some lactobacilli in the intestines — 10-hydroxy-cis-12-octadecenoic acid (10-HSA). In experiments on mice, it simultaneously restored the liver and repaired the “leaky” intestinal wall after a toxic attack by aflatoxin, a classic model of damage along the “gut-liver” axis. The key to the effect is the activation of the lipid metabolism regulator PPARα, which is often “switched off” in chronic liver diseases. The work was published in mBio on August 12, 2025.

Background

• Why look at the gut-liver axis at all? The liver receives blood directly from the gut via the portal vein, along with microbial molecules and metabolites ranging from short-chain fatty acids to bile acids and lipopolysaccharides. Gut barrier disruption and dysbiosis increase inflammation and metabolic stress in the liver, which is implicated in NAFLD and other chronic liver diseases. This is the long-established concept of the gut-liver axis.
• Where is PPARα? The nuclear receptor PPARα is the master “switch” for fatty acid oxidation in the liver; its activation improves lipid metabolism, reduces lipotoxicity and inflammation. PPARα agonists (fibrates) are already being considered as an option in MASLD; there is growing interest in strategies that “turn on” PPARα more physiologically.
• Aflatoxin as a real and experimental problem. Aflatoxin B1 is a mold toxin ( Aspergillus ) that can damage the liver and simultaneously "shake up" the intestinal barrier (oxidative stress, inflammation), which causes an increase in the flow of inflammatory signals to the liver. Therefore, it is often used to model breakdowns along the "gut-liver" axis.
• Microbial acids of the HYA/10-HSA series — where they come from. A number of Lactobacillus can convert linoleic acid into 10-hydroxy-cis-12-octadecenoic acid (synonyms in the literature: HYA/10-HSA) and related compounds (KetoA, KetoC, etc.). Back in 2013–2014, it was shown that these metabolites are actually formed in the intestine and are capable of strengthening the intestinal epithelial barrier in inflammation models. That is, they already had a “biological reputation” before the current work.
• From "probiotics" to point metabolites. The field is moving away from crude interventions (bacterial cocktails) to targeted microbial metabolites with a clear target (sometimes called "postbiotics", although according to the ISAPP consensus, pure metabolites are not formally considered postbiotics). The idea is to give an effector molecule with predictable pharmacology and without the risk of overpopulating the intestine with unnecessary strains.
• What exactly does the current paper add? The authors showed that a single microbial molecule, 10-HSA, can simultaneously: (i) repair the gut barrier and (ii) restore hepatic lipid metabolism via PPARα in mice after aflatoxin toxicity. In doing so, they have “connected” the two ends of the gut-liver axis in a single intervention and identified a candidate class of “microbial drugs” for NAFLD.
• Why this seems plausible biologically. The link “gut barrier ↔ flow of inflammatory triggers ↔ liver metabolism” is supported by reviews, and PPARα logically explains shifts in the bile acid profile and energy metabolism of the liver. In this context, 10-HSA is not a random “vitamin”, but a link in a known regulatory network.

What did they do?

The team modeled metabolically associated fatty liver disease/nafld (MASLD/NAFLD) disorders in mice using aflatoxin B1, a mold toxin that damages the liver and exacerbates inflammation and leakiness in the gut barrier. They then gave the animals 10-HSA, a metabolite naturally produced by Lactobacillus in response to inflammation. The results were reversible improvements in two organs: tight junctions in the intestinal epithelium were restored, energy metabolism and detoxification pathways in the liver were normalized, and bile acid profiles (including cholesterol and deoxycholate) were shifted toward a “healthy” profile.

How does this work

10-HSA activates the PPARα “switch” protein, which is responsible for burning fat and fine-tuning lipid metabolism in the liver. When PPARα “wakes up,” inflammation quiets down, fibrotic signaling (such as the TGF-β axis) decreases, and cells cope better with the toxic load. At the same time, the intestinal barrier is strengthened, which reduces the flow of toxins and bacterial molecules into the blood — and, therefore, reduces the flow of inflammatory triggers to the liver. In essence, one molecule “repairs” the intestinal-liver axis from both ends at once.

Why is this important?

• The scale of the problem. MASLD/NAFLD is one of the most common chronic liver diseases in the world; affordable, safe, and targeted treatments are few. Therapies that act simultaneously on the liver and gut are in short supply—the link that is often broken in the disease.
• Origin matters. 10-HSA is a natural product of the microbiota and has not shown cytotoxicity in preclinical tests. The idea of “targeted” microbial metabolic therapy may become an alternative to the crude interventions in the microbiota with whole probiotic cocktails.
• Aflatoxin is a real threat. In regions with food contamination risks (peanuts, corn, etc.), aflatoxin remains an important factor in liver damage. If 10-HSA proves effective in humans, it could be used as a preventive supplement for risk groups.

What exactly did they see in the mice?

• Intestines: restoration of the epithelial barrier and normalization of the local immune response.
• Liver: Improved energy metabolism, enhanced detoxification functions, shifted bile acids to a “healthy” range.
• Systemic effect: The action of 10-HSA is consistent with the activation of PPARα, a key regulator of lipid metabolism, which is often suppressed in chronic liver diseases.

What about security?

Preclinical experiments have not revealed toxicity or cytotoxic effects of 10-HSA — plus, it is important that the molecule is normally produced by “its own” intestinal bacteria. This does not cancel out thorough testing on people, but the entry threshold looks more favorable than that of synthetic candidates.

What's next?

The authors are preparing a transition to clinical trials, primarily in patients with fatty liver disease or metabolic disorders. A separate area is prevention in regions with high aflatoxin exposure. Conceptually, the work pushes towards a new class of agents: not a “probiotic as a strain,” but a verified microbial metabolite with a clear target and predictable pharmacology.

Reference

• 10-HSA is a fatty acid produced by some Lactobacillus bacteria and is thought to act as a “microbial medicine” for the gut-liver axis.
• PPARα is a nuclear receptor that controls fatty acid oxidation and lipid metabolism in the liver; its activation reduces lipotoxicity and inflammation.
• Aflatoxin B1 is a mold toxin ( Aspergillus ), a common cause of liver damage in countries with food storage and control problems.

Source: mBio article (August 12, 2025) and UC Davis/EurekAlert and Technology Networks press materials summarizing key findings from the study ( DOI: 10.1128/mbio.01718-25 ).