Impact of a Probiotic Supplementation With Lifestyle Modification on Liver Steatosis, Fibrosis, and Metabolic Health in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Official title

Impact of a Multi-strain Probiotic Supplementation With Lifestyle Modification on Liver Steatosis, Fibrosis, and Metabolic Health in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Overview

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the new clinical term introduced in 2023 to redefine what was formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD). It is defined as fatty liver confirmed by imaging or biopsy, accompanied by at least one cardiometabolic risk factor (e.g., hyperglycemia, dyslipidemia, hypertension, or obesity). Its pathological progression ranges from simple steatosis to steatohepatitis, primarily driven by excessive energy intake, hepatic lipid accumulation, and insulin resistance. MASLD is currently the most prevalent chronic liver disease globally, with a prevalence rate of approximately 30-40%. However, there is no satisfactory pharmacological treatment, leaving lifestyle modification as the primary therapeutic approach. Many patients struggle to effectively adjust their habits, leading to persistent hepatic inflammation and damage, which may eventually progress to end-stage diseases such as cirrhosis and hepatocellular carcinoma. In many developed countries, MASLD has become the leading indication for liver transplantation, imposing a heavy burden on healthcare systems. Gut dysbiosis is closely linked to MASLD. An imbalance in the gut microbiota disrupts the gut-liver axis, leading to impaired intestinal mucosal barrier function. This allows bacterial components to enter the circulation, further triggering hepatic inflammation and abnormal lipid metabolism. Consequently, modulating the gut microbiota is considered a potential therapeutic strategy. Over the past decade, probiotics, prebiotics, and synbiotics have been extensively studied as non-pharmacological treatments for NAFLD. Multiple studies indicate that these products can reduce liver enzymes (AST, ALT), insulin resistance (HOMA-IR), and inflammatory markers (hs-CRP, TNF-α). The most effective combinations typically involve Lactobacillus, Bifidobacterium, and Streptococcus, with a recommended duration of approximately 12 weeks. However, the impact of these products on liver fibrosis, hepatic fat accumulation, and cardiometabolic risk factors remains inconclusive. The probiotic product to be tested consists of Lactobacillus salivarius AP-32, Lactobacillus rhamnosus bv-77, Bifidobacterium animalis CP-9, and Lactobacillus reuteri GL-104. This formulation complies with food safety regulations. In clinical studies, it had been proven as an effective adjuvant method that increased beneficial gut bacteria such as Akkermansia muciniphila and improved the control of blood glucose, lipids, and inflammatory markers. Study Objectives This study aims to investigate the efficacy of this probiotic product as an adjuvant therapy alongside lifestyle modifications in adult patients with MASLD. We will evaluate its impact on: 1. The degree of liver fibrosis and steatosis 2. Cardiometabolic risk factors (BMI, waist circumference, blood lipids, and blood glucose). 3. Inflammatory markers. 4. Gut microbiota composition.

Interventions

• Dietary supplement Probiotic product
  The probiotic product contains Lactobacillus salivarius AP-32, Lactobacillus rhamnosus bv-77, Bifidobacterium animalis CP-9 and Lactobacillus reuteri GL-104
• Behavioral Life style modification
  Life style modification of MASLD provided by an gastroenterologist in an outpatient s
• Dietary supplement placebo
  placebo sachet looked and taste very similar to the probiotic product being tested

Primary outcome measures

• Change in shear wave elastography (m/s) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]

Secondary outcome measures (12)

• Change in ultrasound attenuation coefficient (dB/cm/MHz) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood LDL level (mg/dL) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood HDL level (mg/dL) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood total cholesterol level (mg/dL) at 12 weeks [Time frame: Time Frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood triglycerides level (mg/dL) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in HOMA-IR at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood fasting insulin level (μU/mL) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood fasting glucose level (mg/dL) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood AST level (U/L) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood ALT level (U/L) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood gamma-GT level (U/L) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in blood alkaline phosphatase level (IU/L) at 12 weeks [Time frame: From enrollment to the end of treatment at 12 weeks]

Eligibility criteria

Inclusion criteria

• ALT ≥ 60 U/L
• Liver steatosis identified by ultrasound
• Meet at least one cardiometabolic criteria:

• BMI ≥ 25 kg/m2 (Asian ≥23)
• Waist circumference: > 94cm (M) 80cm(F)
• Fasting blood glucose ≥ 100 mg/dL
• HbA1c ≥ 5.7
• Receiving treatment of diabetes
• Receiving treatment of Hypertension
• Average home blood pressure: ≥ 130/85 mmHg
• TG ≥ 150 mg/dL
• HDL ≤ 40 mg/dL
• Receiving treatment of dyslipidemia

Exclusion criteria

• HBsAg(+)
• Anti-HCV (+)
• Cirrhosis
• Excessive alcohol intake ( Male over 210g/wk; Female over 140mg/wk)
• Could not rule out Autoimmune hepatitis (ANA, or AMA or ASMA (+))
• Could not rule out drug related hepatitis
• Receiving drug that might induce liver steatosis:
• Glucocorticoids
• Amiodarone
• Tamoxifen
• Methotrexate
• Valproate
• Tetracycline
• Chemotherapeutic agents
• Receiving immune modulators or biologics
• Receiving antibiotics within 1 month
• Receiving any cancer treatment
• Have diagnosis of "Catastrophic Illness" defined by Health Administration of Taiwan
• eGFR<60
• Pregnancy
• Currently enrolled in other dietary or pharmacology clinical trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 2 centers

• Fu Jen Catholic University Hospital — New Taipei City
• Fu Jen Catholic University Hospital — New Taipei City

Publications

• Abhari K, Saadati S, Yari Z, Hosseini H, Hedayati M, Abhari S, Alavian SM, Hekmatdoost A. The effects of Bacillus coagulans supplementation in patients with non-alcoholic fatty liver disease: A randomized, placebo-controlled, clinical trial. Clin Nutr ESPEN. 2020 Oct;39:53-60. doi: 10.1016/j.clnesp.2020.06.020. Epub 2020 Jul 24. PMID 32859329
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• Farrow A, Farrow SC, Little R, Golding J. The repeatability of self-reported exposure after miscarriage. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Int J Epidemiol. 1996 Aug;25(4):797-806. doi: 10.1093/ije/25.4.797. PMID 8921459
• Jansson JH, Boman K, Brannstrom M, Nilsson TK. High concentration of thrombomodulin in plasma is associated with hemorrhage: a prospective study in patients receiving long-term anticoagulant treatment. Circulation. 1997 Nov 4;96(9):2938-43. doi: 10.1161/01.cir.96.9.2938. PMID 9386160
• Yang Y, Yang L, Wu J, Hu J, Wan M, Bie J, Li J, Pan D, Sun G, Yang C. Optimal probiotic combinations for treating nonalcoholic fatty liver disease: A systematic review and network meta-analysis. Clin Nutr. 2024 Jun;43(6):1224-1239. doi: 10.1016/j.clnu.2024.04.004. Epub 2024 Apr 13. PMID 38643738
• Wu J, Chen X, Qian J, Li G. Clinical improvement effect of regulating gut microbiota on metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis of randomized controlled trials. Clin Res Hepatol Gastroenterol. 2024 Aug;48(7):102397. doi: 10.1016/j.clinre.2024.102397. Epub 2024 Jun 13. PMID 38879003
• Sharma S, Tiwari N, Tanwar SS. The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep;398(9):11541-11579. doi: 10.1007/s00210-025-04069-z. Epub 2025 Apr 9. PMID 40202676

Identifiers

NCT: NCT07400367 · FJUH114502

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗