Bernd Schnabl
University of California-San Diego, CA·Medicine & Clinical Research
Heavy drinking damages the liver, but much of that damage appears to begin in the gut. Chronic alcohol use shifts the community of microbes living in the intestine and makes the intestinal lining leaky, so microbial products can travel to the liver and drive inflammation and injury.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Physiology
- Topics
alcohol-associated liver disease
alcoholic hepatitis
alcohol use disorder
- Grants
- 6 known grants, through Jun 2031
What they work on
- Test whether the sugar-adding enzyme Fucosyltransferase 2 (Fut2) on intestinal lining cells limits colonization and translocation of the gut bacterium Enterococcus faecalis and thereby reduces liver disease, using mouse models of ethanol feeding.
- Determine how CRIg, a receptor on liver Kupffer cells that engulfs bacteria, contributes to clearing Enterococcus faecalis and to liver injury, and test new strategies to prevent or ameliorate ethanol-induced liver disease in preclinical models.
- Test whether fecal levels of the protease Cathepsin B correlate with clinical severity and outcome in patients with alcohol-associated liver disease, by profiling host proteases in stool samples and intestinal biopsies.
- Define the source, regulation and protein substrates of Cathepsin B in gut barrier breakdown using mouse intestinal macrophages, human intestinal organoids, and mice lacking Cathepsin B in myeloid cells under chronic-plus-binge ethanol feeding.
- Test the gut-restricted Cathepsin B inhibitor CA-074 as an oral intervention to stabilize intestinal tight junctions and reduce liver disease in ethanol-fed mice.
- Test whether overgrowth of the fungus Candida albicans drives expansion of interleukin-17-producing Th17 cells that inflame and damage the liver, using a human cohort plus antifungal drugs, fungal supplementation and genetically modified mice.
- Test whether the fungus Malassezia restricta worsens alcohol-associated liver disease by binding the Dectin-2 receptor on liver Kupffer cells, using ethanol-fed mice.
- Evaluate the safety and feasibility of capsule-based fecal microbiota transplantation in eight patients with auto-brewery syndrome, tracking flares with blood and breathalyzer ethanol, diet records, and stool microbiome and anaerobic bioreactor assays.
- Operate center cores providing human biospecimens, gnotobiotic and conventional mouse phenotyping, and sequencing with bioinformatics, and run Pilot/Feasibility awards plus seminars, symposia and workshops for digestive disease investigators and trainees.
More about the research
Alcohol-associated liver disease affects several million people in the United States, and alcohol is the leading cause of liver cirrhosis in industrialized countries. The research program asks which gut microbes and host molecules drive liver injury, how alcohol lets them reach the liver, and whether blocking those steps protects it. Projects cover gut bacteria and their toxins, host enzymes that digest the gut barrier, and intestinal fungi. A separate clinical trial addresses a rare condition in which gut microbes themselves produce alcohol, and the PI also leads a regional center supporting digestive disease research.
Why it matters
Alcohol-associated liver disease affects millions of Americans and is the leading cause of cirrhosis in industrialized countries, yet the mechanisms linking drinking to gut leakiness and liver injury are poorly understood. Identifying the bacteria, fungi, toxins and host enzymes involved could yield new drug targets and preventive strategies, including gut-restricted protease inhibitors. For patients with auto-brewery syndrome, who currently have no accepted therapy, the trial tests whether fecal microbiota transplantation is safe and feasible.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xiaoqin Wu
University of Texas Health Science Center at Houston, TX·Microbiology & Immunology·Early-career
Characterize liver immune cell populations and cell death after Gao-binge alcohol feeding in Mlkl bone-marrow chimeric mice, using flow cytometry of isolated non-parenchymal liver cells.
David Goldberg
University of Miami, FL·Medicine & Clinical Research
Develop risk prediction models for transplant-free survival among patients with alcohol-associated liver disease who have limited access to transplant, to identify those most in need of early liver transplant referral.
Karuna Rasineni
University of Nebraska Medical Center, NE·Physiology
Determine how alcohol-induced ghrelin alters gut-liver communication through GLP-1, a gut hormone that regulates energy use, and whether ghrelin blocks GLP-1's effects on liver cell metabolism during alcohol-associated fatty liver.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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