Effects of Probiotics (P. Pentosaceus, L. Lactis or L. Helveticus) in NASH

Effects of Probiotics (P. Pentosaceus, L. Lactis or L. Helveticus) in Patients With Nonalcoholic Hepatitis

A study for evaluating the improvement effect on Metabolic dysfunction-associated steatotic liver disease (MASLD) of probiotics

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with dysbiosis of the gut microbiota and altered host metabolic homeostasis. Probiotics have been proposed as a potential therapeutic strategy to modulate gut microbial composition and improve metabolic and hepatic outcomes in MASLD; however, clinical evidence regarding next-generation probiotic strains remains limited.

This study was designed to evaluate the effects of three next-generation probiotic strains-Lactobacillus delbrueckii subsp. lactis (LL001), Lactobacillus helveticus (LH001), and Pediococcus pentosaceus KID7 (PPKID7)-on liver function parameters and gut microbiome composition in patients with MASLD.

We conducted a randomized, double-blind, placebo-controlled, parallel-group clinical trial. A total of 110 adult patients diagnosed with MASLD were screened for eligibility. Eligible participants were randomly assigned to receive one of the three probiotic formulations (3 capsules per day, total 9×10⁹ CFU) or placebo for 8 weeks. All participants received concomitant silymarin during the intervention period.

Clinical assessments, serum samples, and stool samples were collected at baseline and at the end of the intervention. Liver function parameters were predefined as the primary outcome measure. Secondary outcomes included changes in anthropometric parameters, serum metabolic markers, gut microbiota composition assessed by 16S rRNA gene sequencing, and lipidomic profiles derived from serum and fecal samples. Compliance was monitored throughout the study period.

The study protocol was approved by the institutional review board, and written informed consent was obtained from all participants prior to enrollment.

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Fatty Liver Disease; MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease
• Intervention / Treatment: Dietary supplement: Probiotics

Detailed Description

Metabolic dysfunction-associated fatty liver disease applies to adults exhibiting hepatic steatosis identified through imaging techniques, blood biomarkers, or liver histology. This diagnosis is made in individuals who are overweight or obese, or who have type 2 diabetes mellitus, or at least two other metabolic risk abnormalities. Subsequently, in June 2023, a multi-society Delphi consensus statement was issued on a revised nomenclature for fatty liver diseases. This statement introduced the term metabolic dysfunction-associated steatotic liver disease (MASLD), effectively replacing the previous nonalcoholic fatty liver disease. Representative etiologies of MASLD are known to include insulin resistance, lipid toxicity due to excessive fat accumulation, inflammatory response, and endoplasmic reticulum stress.

The global rise in obesity has contributed to the increased prevalence of MASLD. MASLD affects approximately 30% of the global adult population, with its prevalence rising from 22% to 37% between 1991 and 2019. This increase aligns with the growing rates of obesity and related conditions worldwide. The more severe manifestation of MASLD, known as metabolic dysfunction-associated steatohepatitis (MASH), is histologically characterized by lobular inflammation and hepatocyte ballooning and is linked to a higher risk of fibrosis progression. Among individuals diagnosed with MASLD who do not meet criteria for a liver biopsy, the prevalence of MASH is approximately 7%. MASLD is one of the most common causes of chronic liver disease and liver-related death and serves as a risk factor for extrahepatic diseases such as diabetes and cardiovascular disease. As a result, the burden of social and economic costs caused by the disease is increasing.

Recently, interest in the role of the gut microbiome in the pathogenesis and treatment of liver diseases has increased, and the disease linkage caused by intestinal bacterial imbalance has been identified [16, 17]. Animal studies have demonstrated potential causal roles of the gut microbiota in MASLD [18, 19]. Human studies have described microbiome alterations in healthy individuals and patients with MASLD and have found several consistent specific taxa that differentiate between healthy individuals and patients with MASLD and advanced liver disease. Despite unknown mechanisms and lack of validation, therapeutic strategies utilizing the gut microbiome have the potential to provide beneficial effects in patients with MASLD.

Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. In our previous animal studies, Lactobacillus and Pediococcus supplementation improved MASLD by modulating gut microbiota and inflammation. Additional experiments with candidate strains have shown promising results in the prevention of MASLD progression. Several randomized controlled trials using ultrasonography and MASLD diagnostic markers of short duration have suggested that administration of probiotics may have a positive effect on hepatic steatosis and insulin resistance in patients. However, none of the previous studies reported the therapeutic effect of probiotics on the microbiome in patients with MASLD. In this clinical trial, we aimed to investigate whether administering probiotics for 8 weeks could effectively improve blood biochemical parameters and induce alterations in the gut microbiota among patients diagnosed with MASLD.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Korea
  • Gangwon-do
    • Chuncheon, Gangwon-do, South Korea, 200-704
      • Hallym University Chuncheon Sacred Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 62 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Those who agreed to participate in this study and signed a written consent
2. Adult men and women over 20

3. Patients diagnosed with non-alcoholic fatty liver

   ※ Exclusion criteria for alcoholic liver disease

   • Those who have an alcoholic drinking ability of at least 60g per day for at least one year before visiting (30g for women)
   • 1 bottle of shochu 360 ml * 20% = 72 g, 1 bottle of beer 500 ml (330 ml for commercial use) * 5% = 25 (16.5 g)

4. Patients with higher liver numbers than normal ※ Adult normal liver level range by enzyme

   • AST, ALT: 40 or less
   • ALP: 20-130
   • GOT: 0-30, GPT: 0-38
   • GGT: 10-62 (male), 7-35 (female)

Exclusion Criteria:

1. Those who have consumed probiotics (lactic acid bacteria, etc.), prebiotics (dietary fiber, fructooligosaccharide, etc.), new biotics, fermented milk, etc. within the past month.
2. Those who have continuously taken antibiotics within the last 2 months or who are likely to take them during the study period
3. Those who have continuously consumed medicines or health functional foods that affect liver function within the past month.
4. Those who have participated in other clinical trials within the past 1 month (but not applicable to medical device clinical trials)

5. If you have any of the following

   • Alcoholic liver disease, hereditary metabolic disease, autoimmune hepatitis
   • systemic inflammatory disease or immune disease
   • Hepatocellular carcinoma
   • Uncontrolled cardiopulmonary disease
   • Other serious systemic disorders in the heart, lungs, blood, and endocrine system
6. A person with a history of malignancy diagnosis within the last 5 years
7. Pregnant or lactating women
8. Persons who have hypersensitivity to the test drug / placebo or components contained in the test drug / placebo or have severe allergic reactions
9. Those who are not suitable for the clinical trial because the investigator judges

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics group; The selected test subjects were randomly assigned to test group 1, test group 2, test group 3, or control group according to the order registered at visit 2 (week 0) after a 2-week run-in period, and for 8 weeks, the study drug or study After taking the treaty, analyze the results of the observations.	Dietary supplement: Probiotics; Experimental group Main ingredients: P. pentosaceus KID7, L. lactis CKDB001 or L. helveticus CKDB001 (containing 9 × 10^9 CFU / day); Control group Main ingredient: Crystalline cellulose; Other Names: Cellulose (Placebo)
Placebo Comparator: Placebo group; The selected test subjects were randomly assigned to test group 1, test group 2, test group 3, or control group according to the order registered at visit 2 (week 0) after a 2-week run-in period, and for 8 weeks, the study drug or study After taking the treaty, analyze the results of the observations.	Dietary supplement: Probiotics; Experimental group Main ingredients: P. pentosaceus KID7, L. lactis CKDB001 or L. helveticus CKDB001 (containing 9 × 10^9 CFU / day); Control group Main ingredient: Crystalline cellulose; Other Names: Cellulose (Placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic characteristics	The gender, date of birth, age, menstruation, and amenorrhea, FAMILY HISTORY	1 week
Primary Outcomes; Liver Function Test	Primary outcomes of liver function enzyme level (AST, ALT, rGT, CHOL, ALP)[IU/L]	Baseline of AST, ALT, rGT, CHOL, and ALP at first week.
Gut-Microbiome Composition	Change of the species and proportions of the gut microbiome. Proportion of phyrum level Composition of F/B ratio	Change from Baseline of fecal microbiome at 8 months
Computed Tomography	change of the Abdominal ultrasonography or Computed Tomography(CT): Upper abdominal ultrasound or CT to determine the degree of fatty liver disease ② Fibroscan: Objectively and quantitatively grasp the degree of liver fibrosis by measuring the degree of firmness (elasticity) of the liver	Change from Baseline of CT image at 8 months
change of BMI	Compare the body mass index. BMI=Body Weight/(Height)^2	Change from Baseline BMI and weight at 6 months
Secondary Outcomes; Liver Function Test	Secondary outcomes of liver function enzyme level (AST, ALT, rGT, CHOL, ALP)[IU/L]	Change from Baseline of AST, ALT, rGT, CHOL, and ALP at 8 months

Collaborators and Investigators

• Sponsor: Chuncheon Sacred Heart Hospital
• Collaborators: Chong Kun Dang Pharmaceutical

Publications and helpful links

General Publications

• Won SM, Joung H, Park IG, Han SH, Ham YL, Han JS, Kwon Y, Kim DJ, Suk KT. The effects of next generation probiotics on metabolic dysfunction-associated steatotic liver disease: a parallel, double-blind, randomized, placebo-controlled trial. J Transl Med. 2025 Dec 9;24(1):61. doi: 10.1186/s12967-025-07478-z.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2020
• Primary Completion (Actual): September 11, 2022
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Probiotics; Gut microbiota; Liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Fatty Liver; Liver Diseases; Non-alcoholic Fatty Liver Disease; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Carbohydrates; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Polysaccharides; Glucans; Biopolymers; Probiotics; Cellulose
• Other Study ID Numbers: PRO-NASH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Personal data is regulated by IRB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No