UC Davis Researchers Discover Gut Bacteria Molecule That Reverses Liver Damage and Repairs Intestinal Barrier

UC Davis Health researchers have made a groundbreaking discovery that could transform treatment approaches for liver disease and gut dysfunction. Their study, published in mBio, reveals that 10-hydroxystearic acid (10-HSA), a natural molecule produced by Lactobacillus bacteria, can simultaneously reverse liver damage and repair intestinal barrier function after toxic exposure.

The research represents the first demonstration of a single microbial molecule capable of healing both organs within the gut-liver axis, according to lead author Satya Dandekar, distinguished professor and chair of the Department of Medical Microbiology and Immunology at UC Davis Health.

Targeting the Gut-Liver Connection

The gut-liver axis represents a critical therapeutic target, as these organs communicate through bile acids, immune responses, and lipid metabolism. When one organ suffers damage, the other inevitably follows. This interconnection becomes particularly relevant in non-alcoholic fatty liver disease (NAFLD), now also called MASLD, which affects more than 1 in 4 adults in the United States.

"NAFLD prevalence is on the rise in the United States. It has increased globally over 50% in the last 30 years," Dandekar explained. "Chronic liver diseases like NAFLD disrupt lipid metabolism and generate high levels of inflammation, also impacting gut health. It limits the gut digestive functions and breaks down the epithelial barrier."

Despite the crucial role this axis plays in maintaining homeostasis, treatments targeting both organs simultaneously remain under-investigated.

Dramatic Therapeutic Effects in Preclinical Studies

The research team used a mouse model that mimics NAFLD by exposing animals to aflatoxin B1 (AFB1), a toxic compound produced by Aspergillus fungi. This exposure triggered liver injury, inflammation, and damage to the gut lining, creating conditions similar to those seen in human liver disease.

Treatment with 10-HSA produced remarkable therapeutic effects across multiple parameters:

• Complete restoration of the gut epithelial barrier
• Normalization of key bile acid metabolites including cholesterol and deoxycholate
• Improved energy metabolism and detoxification functions in the liver
• Normalized gut immune responses

Mechanism of Action Through PPAR⍺ Activation

The therapeutic effects of 10-HSA operate through activation of PPAR⍺ (search)Search target, a protein that regulates lipid metabolism. Chronic liver diseases like NAFLD and cirrhosis are driven partly by suppression of PPAR⍺ signaling. By activating this pathway, 10-HSA repairs liver tissue and supports gut health without the side effects associated with synthetic drugs.

"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."

Co-author Abhaya Dandekar, a professor of plant sciences at UC Davis, emphasized the molecule's unique properties: "What makes this molecule special is that it is produced naturally in the gut and has no cytotoxic effects. It works only when the body and the microbiome are in sync."

Addressing Global Health Challenges

The discovery has particular relevance for aflatoxin exposure, which affects many people globally, especially in developing countries with poor food safety standards. Aflatoxin, commonly found in peanuts, corn, and other crops, represents a serious public health concern in agricultural areas.

First author Dylan Kramer, a graduate student in Dandekar's lab, highlighted the potential impact: "It would truly be a unique and exciting opportunity if we can provide a microbially-derived supplement that can alleviate or prevent the detrimental impact on human health."

Expanding Beyond Traditional Microbiome Research

The study also represents a shift in microbiome research focus. While scientists have traditionally concentrated on short-chain fatty acids (SCFAs) produced by gut bacteria, this work explores larger, more complex metabolites.

"While SCFAs are very important, our study serves as one of the first to broaden the focus to larger, more complex metabolites produced in direct response to pro-inflammatory conditions in the gut," Kramer explained.

Clinical Translation on the Horizon

With strong preclinical evidence and no toxicity concerns identified, the researchers are preparing for human clinical trials, particularly targeting patients with fatty liver disease or metabolic disorders. The study highlights the powerful therapeutic potential of the microbiome and suggests how tapping into this natural pharmacy could transform medical treatment approaches.

The research lays the foundation for developing simple, safe supplements that could provide life-changing benefits for patients suffering from liver disease and associated gut dysfunction.