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)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 80
- Locations
- 2
- Primary Endpoint
- Change in shear wave elastography (m/s) at 12 weeks
Study Overview
Brief Summary
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:
- The degree of liver fibrosis and steatosis
- Cardiometabolic risk factors (BMI, waist circumference, blood lipids, and blood glucose).
- Inflammatory markers.
- Gut microbiota composition.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
- •Pregnancy
- •Currently enrolled in other dietary or pharmacology clinical trial
Arms & Interventions
Intervention
Receive the probiotic product one sachet per day and standard lifestyle modification education for MASLD by a gastroenterologist.
Intervention: Probiotic product (Dietary Supplement)
Intervention
Receive the probiotic product one sachet per day and standard lifestyle modification education for MASLD by a gastroenterologist.
Intervention: Life style modification (Behavioral)
Placebo
Receive the placebo one sachet per day and standard lifestyle modification education for MASLD by a gastroenterologist.
Intervention: Life style modification (Behavioral)
Placebo
Receive the placebo one sachet per day and standard lifestyle modification education for MASLD by a gastroenterologist.
Intervention: placebo (Dietary Supplement)
Outcomes
Primary Outcomes
Change in shear wave elastography (m/s) at 12 weeks
Time Frame: From enrollment to the end of treatment at 12 weeks
Change in liver fibrosis at 12 weeks
Secondary Outcomes
- Change in ultrasound attenuation coefficient (dB/cm/MHz) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood LDL level (mg/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood HDL level (mg/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood total cholesterol level (mg/dL) at 12 weeks(Time Frame: From enrollment to the end of treatment at 12 weeks)
- Change in blood triglycerides level (mg/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in HOMA-IR at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood fasting insulin level (μU/mL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood fasting glucose level (mg/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood AST level (U/L) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood ALT level (U/L) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood gamma-GT level (U/L) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood alkaline phosphatase level (IU/L) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood BUN level (mg/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood Creatinine level (mg/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in eGFR level (mL/min/1.73m^2) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood albumin level (g/dL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in platelet level (*10^3/uL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in HbA1c level (%) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood hs-CRP level (mg/L) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood IL-6 level (pg/mL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood TNF-alpha level (pg/mL) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in Fib-4 score at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in ARPI score at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in NAFLD Fibrosis Score at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in blood pressures (mmHg) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in body weight (kg) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in BMI (kg/m^2) at 12 weeks(From enrollment to the end of treatment at 12 weeks)
- Change in waist circumference (cm) at 12 weeks(From enrollment to the end of treatment at 12 weeks)