Developing Microbial Therapy for MASLD: From Mechanism to Clinical Validation (MASLD)

March 18, 2026 updated by: Leeuwenhoek Laboratories Co. Ltd.

Development of Microbial Therapeutics for Metabolic Dysfunction-Associated Steatotic Liver Disease: From Mechanistic Investigations to Clinical Trials

Metabolic dysfunction-associated steatotic liver disease (MASLD), redefined in 2020, is an improved diagnostic standard evolved from non-alcoholic fatty liver disease (NAFLD), emphasizing the correlation between hepatic steatosis and metabolic dysfunction. Compared to NAFLD, which relies on exclusion-based diagnosis, MASLD criteria enhance population homogeneity in studies and accommodate patients with coexisting liver diseases, thereby improving the efficiency and relevance of drug development. MASLD affects approximately one-quarter of the global population. If left untreated, it may progress to liver fibrosis, cirrhosis, or hepatocellular carcinoma. Given its high clinical burden and the current lack of FDA-approved therapies, effective treatments for MASLD are urgently needed.

Previous studies suggest that diet and gut microbiota play crucial roles in the pathogenesis of MASLD. Dietary composition influences microbial balance and intestinal barrier function. In dysbiosis, gut-derived harmful substances such as pathogen-associated molecular patterns (PAMPs) and microbiota-derived metabolites (MDMs) may translocate via a leaky gut to the liver through the portal vein, contributing to hepatic injury. These processes, often described as the gut-liver axis, remain incompletely understood.

Animal studies have shown that dietary components regulating gut microbiota may help alleviate MASLD. While clinical evidence remains limited, incorporating microbiota-modulating and immune-regulating food ingredients holds potential. Next-generation probiotics have demonstrated benefits in improving hepatic lipid metabolism and modulating gut microbiota, potentially slowing MASLD progression through gut-liver axis modulation.

Our previous research investigated a pasteurized Akkermansia muciniphila strain, NTUH_Amuc03 (pAKK_LWHK0003), which attenuated fatty liver progression in preclinical models. In mice subjected to a high-fat, high-fructose, high-cholesterol diet, pAKK_LWHK0003 administration resulted in reduced body weight, improved dyslipidemia, lowered NAFLD activity scores, and improved HOMA-IR. These findings support the potential of pAKK_LWHK0003 in slowing MASLD progression.

This study aims to evaluate further the clinical efficacy and safety of pAKK_LWHK0003 in individuals with MASLD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The aim of this study was to evaluate the effects of administering indigenously derived inactivated Akkermansia muciniphila (pAKK_LWHK0003) on improving fatty liver in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess its clinical safety.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
        • Principal Investigator:
          • Ming-Shiang Wu
        • Contact:
        • Sub-Investigator:
          • Chun-Jen Liu
        • Sub-Investigator:
          • Wei-Kai Wu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Fibroscan，CAP ≧ 260db/m

Exclusion Criteria:

A. Pregnant women or women who are breastfeeding. B. Use of probiotics and prebiotic-related products (including yogurt, yogurt, Yakult, etc.) within 14 days before the screening visit.

C. Patients who have used antibiotics (except skin lotions) or antifungal drugs within 30 days before the screening visit.

D. Use of glucagon-like peptide-1 receptor agonists (GLP1-RAs) within six months prior to the screening visit.

E. Use of drugs that may affect the evaluation index within 14 days before the screening visit, during the screening visit, or during the planned trial period, such as steroids, immunosuppressants, or anti-inflammatory drugs, or drugs containing ingredients for treating hepatitis or affecting fat metabolism, including HMG-CoA reductase inhibitors (statins), fibrates, silymarin, thiazolidinediones, metformin, cholestyramine, ezetimibe, orlistat, and sodium-glucose transporter type 2 inhibitors (SGLT2i). This restriction does not apply if the above-mentioned drugs have been used continuously for more than six months and the dosage is not changed during the trial.

F. Those who have had severe gastrointestinal infection diarrhea symptoms within 14 days before the screening visit (more than three watery stools in 24 hours).

G. Have the following medical history or laboratory abnormalities:

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pasteurized Akkermansia muciniphila LWHK0003 _low dose
400 mg/capsule/day. Duration: 120 days
Biological: Pasteurized Akkermansia muciniphila LWHK0003_low dose
400 mg/capsule/days. Duration: 120 days
Experimental: Pasteurized Akkermansia muciniphila LWHK0003 _medium dose
400 mg/capsule/day. Duration: 120 days
Biological: Pasteurized Akkermansia muciniphila LWHK0003_medium dose
400 mg/capsule/day. Duration: 120 days
Experimental: Pasteurized Akkermansia muciniphila LWHK0003 _high dose
400 mg/capsule/day. Duration: 120 days
Biological: Pasteurized Akkermansia muciniphila LWHK0003_high dose
400 mg/capsule/day. Duration: 120 days
Placebo Comparator: Placebo
400 mg/capsule/day. Duration: 120 days
Other: Placebo
400 mg/capsule/day. Duration: 120 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver steatosis, fibrosis, liver stiffness, and FIB-4 index
Time Frame: From enrollment to the end of treatment, up to 52 weeks
To assess the statistical differences between baseline and Weeks 12 and 16 (Visit V5 and V6) after administration of placebo or different doses (10⁹, 10¹⁰, 10¹¹ CFU) of pAKK LWHK0003 capsules, in terms of liver fat content (steatosis), fibrosis, liver stiffness, and FIB-4 index as measured by FibroScan and MRI/MRE.
From enrollment to the end of treatment, up to 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leeuwenhoek Laboratories Co. Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

February 5, 2025

First Submitted That Met QC Criteria

March 18, 2026

First Posted (Actual)

March 23, 2026

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 18, 2026

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • LL-IRB-2403

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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