Exploring the Role of Probiotics, Prebiotics, and Synbiotics in the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease—A Scoping Review

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver condition. Its prevalence is estimated to further increase. The gut–liver axis, which represents both anatomical and functional connections, contributes significantly to the development of MASLD. Dysbiosis, characterized by an imbalance in gut microbiota, can exacerbate the disease by increasing intestinal permeability, which permits harmful bacteria and their components to enter the bloodstream. This review sought to explore the impact of probiotics, prebiotics, and synbiotics on the treatment of MASLD. Method: The methodology for scoping reviews in accordance with Prisma-ScR guidelines was followed. A comprehensive search was conducted in databases such as PubMed, Scopus, and Medline. Out of 1390 studies screened, 25 were selected for the final analysis. Results: The findings of this scoping review highlight the therapeutic potential of probiotics, prebiotics, and synbiotics in the management and treatment of MASLD, as showcased by the existing literature. Conclusions: This scoping review offers important insights into the advantages of probiotics, prebiotics, and synbiotics in the treatment of MASLD. The limitations identified in this study emphasize the necessity for larger, long-term, and geographically diverse studies in order to obtain more solid scientific results.

1. Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver condition, closely linked to type 2 diabetes (T2D), obesity, as well as other cardiometabolic risk factors [1]. MASLD is associated with a significant increase in the risk of cardiovascular events, chronic kidney disease, and various cancers, including liver cancer, as well as liver-related complications such as liver failure and hepatocellular carcinoma (HCC) [2].

The term MASLD replaces the former designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the strong link between hepatic steatosis and metabolic dysfunction. It includes a spectrum of conditions, ranging from isolated steatosis and metabolic dysfunction-associated steatohepatitis (MASH) to fibrosis and cirrhosis, and aligns with a broader classification of steatotic liver disease (SLD) that also encompasses alcohol-related and genetically induced liver disorders [2,3].

Globally, MASLD affects approximately 30% of adults, with prevalence rising from 22% to 37% between 1991 and 2019, reflecting concurrent increases in obesity and metabolic syndrome [4,5]. MASH, the more aggressive form, is marked histologically by lobular inflammation and hepatocyte ballooning, often leading to fibrosis [6]. A large, multi-center, Asian cohort showed that 63% of MASLD patients undergoing biopsy were diagnosed with MASH, compared to only 7% among non-biopsied individuals [7].

CVD remains the leading cause of death among MASLD patients, although those with advanced liver fibrosis experience significantly increased liver-related mortality. A cohort study showed cardiovascular events are 2.03 per 100 person-years, convert to 0.43 for liver-related events exclusively in patients with advanced fibrosis [8,9].

The gut–liver axis plays a pivotal role in MASLD pathogenesis. This bidirectional communication system connects the gastrointestinal tract and the liver via the portal vein, bile ducts, and systemic circulation. Roughly, two-thirds of the liver’s blood supply originates from the gut, carrying nutrients and microbial products [10,11]. In return, the liver secrets bile and other bodies that shape the gut microbiota.

Disruption of this balance—gut dysbiosis—leads to increased intestinal permeability or “leaky gut”, allowing endotoxins and microbial products to enter the liver, where they activate immune responses and inflammatory cascades. This perpetuates liver damage and accelerates progression to MASH, fibrosis, or HCC [12]. The multiple-hit hypothesis explains MASLD pathogenesis as a complex interplay of genetic, environmental, and antimicrobial factors [13].

Contributors such as excessive caloric intake, physical inactivity obesity, and dysbiosis impair gut barrier function, allowing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to activate hepatic toll-like receptors (TLRs), notably TLR-4 and TLR-9, through molecules such as lipopolysaccharide (LPS), thus amplifying inflammation and disease progression [14,15].

Interventions such as prebiotics, probiotics, and synbiotics have shown promise in restoring microbial balance, strengthening the gut barrier, reducing systemic inflammation, and slowing MASLD progression. Probiotics enhance beneficial gut flora and immune function; prebiotics promote the growth of these microorganisms; and synbiotics, combining both, offer synergistic benefits [16,17,18]. Fermented foods also provide natural probiotic sources and may play a role in maintaining gut–liver homeostasis [17].

2. Materials and Methods

A literature review in a scoping review design was conducted to examine the effects of probiotics, prebiotics, and synbiotics in the treatment of MASLD [19,20]. Unlike systematic reviews, scoping reviews have distinct characteristics; they do not aim to answer specific research question about a particular intervention. Instead, they systematically explore results, identify variations, and highlight areas that require further investigation. Although the methodology shares some similarities with systematic reviews, scoping reviews do not exclude publications based on specific interventions.

For this scoping review, the PRISMA-ScR guidelines were followed to ensure transparency, methodological rigor, and reproducibility. The PRISMA-ScR checklist provided critical guidance throughout the process, from formulating research questions to data extraction and synthesis. By adhering to these protocols, the structured approach was ensured for this review, documenting the research strategy, inclusion criteria, and data extraction techniques. The protocol for this review was not registered in any publicly accessible repository. The study selection process consisted of two stages which started with title and abstract screening and was followed by full-text eligibility assessment. Two independent reviewers conducted the record screening process and resolved disagreements through discussion or by consulting a third reviewer. The researchers used a standardized form to extract data which included study characteristics and population details and intervention types (probiotics, prebiotics, or synbiotics) and measured outcomes and key findings (Table 1). The data extraction process was performed by one reviewer who received verification from a second reviewer to maintain data accuracy and consistency. This is a comprehensive overview of the current literature on MASLD, enhancing the credibility of the findings in order to make them valuable for researchers, clinicians, and policymakers.

The primary objective of this review was to evaluate the impact of probiotics, prebiotics, and synbiotics on the management of MASLD. The review process consisted of three main stages. The first one consisted of defining the research question and of identifying relevant literature; the second stage was selecting the appropriate studies, and the third one was to organize, to synthesize, and to summarize the information gathered [19,20].

A comprehensive search was carried out across electronic databases, including PubMed, Scopus, CINAHL, Cochrane Library, Web of Science, Embase, and Medline. This search employed the combination of medical subject headings (MeSH) and then three terms such as “probiotics”, “prebiotics”, “synbiotics”, “non-alcoholic fatty liver disease”, and “metabolic dysfunction-associated steatotic liver disease”. From the search, 1390 studies were initially identified, with 24 meeting the inclusion criteria (see Figure 1). Only English language publications available before the end of September 2024 were considered. To ensure relevance to current clinical practice, only studies published within the last ten years (2014–2024) were included. Additionally, a supplementary search was conducted using Google to identify any potentially overlooked studies.

Studies were excluded if they were categorized as comments, opinion pieces, case studies, review articles, book chapters, or if they lacked original data. Eligible studies met the following criteria: randomized controlled trials (RCTs), single- or double-blinded designs, and well-defined intervention and control groups. Studies were excluded if they involved ineligible designs, such as observational or non-randomized studies, lacked original data, or focused on the interventions unrelated to probiotics, prebiotics, or synbiotics.

3. Results

A comprehensive search strategy identified a total of 1390 studies. After removing duplicates, 528 papers were subjected to a full-text review, resulting in 24 studies that met the inclusion criteria and were selected for detailed analysis (refer to Figure 1). The main reasons for excluding the remaining studies were their failure to meet the criteria for randomized controlled trials (RCTs) or their lack of relevance to the primary outcome of the review.

Data extracted from the selected studies were independently categorized by two researchers into four key areas: (1) sample characteristics, intervention duration, and outcomes; (2) type of intervention; (3) effects on MASLD; (4) risk of bias. Disagreements were generally resolved through discussion and mutual agreement. When consensus could not be achieved, a third reviewer was consulted, guided by standardized resolution criteria. The key findings from the RCTs are presented in Table 2, and the results pertaining to the objectives of the review are further elaborated.

3.1. Study Selection

Figure 1 illustrates the literature screening process, which involved reading, assessing, and discussing based on the established inclusion and exclusion criteria. In total, 23 articles related to MASLD were included, with 14, 2, and 11 studies examining the effects of probiotic, prebiotic, and synbiotic interventions, respectively. Additionally, two of these studies assessed the impact of different gut microbiota modulators on MASLD simultaneously.

3.2. Sample

The RCTs included study different sample sizes ranging from 8 to 117 participants diagnosed with NAFLD. The duration of the studies ranged from eight weeks to one year. All the studies were published in the last 20 years, with nine of them performed in Iran [22,23,24,25,26,27,28,29,30], two in the UK [31,32], two in Ukraine [33,34], two in Germany [35,36], one in Korea [37], one in Brazil [38], one in Bangladesh [39], one in Malaysia [40], one in Serbia [41], one in Spain [42], one in Italy [43], and one in India [44].

3.3. Randomization Process

Most of the RCTs included in this scoping review described the randomization methods employed to assign participants to either the intervention or the placebo group. Two studies employed a 1:1 allocation ratio [26,36]. In seven studies, a computer-generated random allocation sequence was implemented [20,22,28,31,32,39,40]. Block randomization was applied in another six studies [25,27,31,32,37]. In the study by Escouto et al. [38], randomization was conducted using www.randomization.com, and the allocation sequence remained concealed throughout the duration of the study. In a study by Alam et al. [39], the allocation of patients was carried out by research physicians who were aware of the study groups, resulting in absence of blinding. In the study by Aller et al. [42], a table of numbers was utilized for the randomization procedure. Derosa et al. [43] implemented randomization through a drawing of envelopes filled with codes, which were prepared by a statistician. The intervention groups of Manzhalii et al. [34], Mofidi et al. [24] and Eslamparast et al. [28] were randomly assigned to receive synbiotic supplementation, although no additional details about their randomization processes were provided.

3.4. Evaluation of Risks of Bias

The risk of bias in each RCT was evaluated using the Cochrane Review framework alongside the NICE methodology checklist [45] designed specifically for RCTs. This checklist assesses several critical domains of bias, including selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data), and reporting bias (selective reporting). The studies included in the review focused on RCTs examining the effects of probiotics, prebiotics, and synbiotics on MASLD-related outcomes.

Most of the studies, including those conducted by Escouto et al. [38], Behrouz et al. [23], Ahn et al. [37], Aller et al. [42], and Kobyliak et al. [33], exhibited robust designs characterized by minimal risks of selection, performance, attrition, and detection biases. Studies by Alam et al. [39] and Manzhalii et al. [34] presented significant selection biases alongside ambiguous performance and detection biases, thereby undermining the credibility of their results. Additionally, skepticism regarding low attrition risks in performance and detection outcomes was noted in studies by Mofidi et al. [24] and Scorletti et al. [31].

Table 1. Included studies.

Study	Sample	Intervention	Duration	Outcome
Escouto et al., 2023 (Brazil) [38] NCT02764047	8	Probiotics (Lactobacillus acidophilus Bifidobacterium lactis) vs. Placebo	6 months	Reduced AST to Platelet Ratio Index (APRI) score; no microbiota change. Glucose: no statistically significant differences between groups at the end of the study.
Behrouz et al., 2020 (Iran) [24] IRCT201410052394N13.	89	Probiotics (Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium longum, and Bifidobacterium breve), Prebiotics (Oligofructose; ORAFTI P95), Control	12 weeks	Lower ALT, AST, GGT in probiotic group. Lower TG, total cholesterol, ALT, AST, GGT in prebiotic group. No significant alterations in the levels of Glu.
Ahn et al., 2019 (Korea) [37] CT0001588	65	Probiotics (Lactobacillus acidophilus, L. rhamnosus, L. paracasei, Pediococcus pentosaceus, Bifidobacterium lactis, and B. breve) vs. Placebo	12 weeks	Reduced intrahepatic fat fraction (IHF), TG, Glu values did not change in either group.
Kobyliak et al., 2018 (Ukraine) [33] NCT03434860	58	Multi-probiotic (Lactobacillus + Lactococcus, Bifidobacterium, Propionibacterium, Acetobacter) vs. Placebo	8 weeks	Lower FLI, AST, GGT, TNF-α, IL-6.
Scorletti et al., 2022 (UK) [31] NCT01680640	104	Synbiotics (fructo-oligosaccharides (4 g/twice day) + Bifidobacterium animalis subsp. lactis BB-12) vs. Placebo	12 months	No liver fat change; weight loss linked with synbiotics. Glu: no statistically significant differences between groups at the end of the study.
Manzhalii et al., 2019 (Ukraine) [34] The trial was not registered in a publicly accessible database	75	Probiotic cocktail (Lactobacillus casei, L. rhamnosus, L. bulgaricus, Bifidobacterium longum, Streptococcus thermophilus and fructooligosaccharides (LBSF)) vs. Control	12 weeks	Lower ALT, stiffness; GGT unchanged. Decreased BMI and serum cholesterol levels, serum glucose remained constantly within the normal range between groups.
Mofidi et al., 2017 (Iran) [24] NCT02530138	50	Synbiotic (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum and Lactobacillus bulgaricus) and prebiotic (125 mg fructo-oligosaccharide) vs. Placebo	28 weeks	Reduced steatosis, inflammation, TAG.
Mohamad Nor et al., 2021 (Malaysia) [40] NCT04074889	39	Multi-strain probiotics (six different Lactobacillus and Bifidobacterium species) vs. Placebo	6 months	No change in steatosis and fibrosis; fasting glucose did not show any significant differences within both groups after the Intervention.
Mantri et al., 2024 (Germany) [35] The trial was pre-registered at Open Science Framework (https://osf.io/utsn4)	117	Synbiotic (Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, and Lactococcus lactis) vs. Placebo	7 weeks	Reduced ALT; alteration in microbiome composition.
Nabavi et al., 2014 (Iran) [25] Not registered	72	Probiotic yogurt (Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12) vs. Conventional	8 weeks	Lower ALT, AST, TC, LDL. Changes in serum. Glucose levels were not significant.
Duseja et al., 2019 (India) [44] No. CTRI/2008/091/000074	39	Probiotics (each capsule containing 112.5 billion live, lyophilised, lactic acid bacteria and bifidobacteria, namely Lactobacillus paracasei DSM 24733, Lactobacillus plantarum DSM 24730, Lactobacillus acidophilus DSM 24735, and Lactobacillus delbrueckii subsp. bulgaricus DSM 24734, Bifidobacterium longum DSM 24736, Bifidobacterium infantis DSM 24737, Bifidobacterium breve DSM 24732, and Streptococcus thermophilus DSM 24731) + Lifestyle mod.	1 year	Improved hepatocyte balloning, lobullar inflammation, NAS, ALT; lower TNF-α. No significant change in the HOMA-IR levels in both groups of patients at 3 and 12 months.
Aller et al., 2011 (Spain) [42] Not registered	30	Probiotics (Lactobacillus bulgaricus and Streptococcus thermophilus) vs. Placebo	3 months	Reduced ALT, AST, GGT.
Derosa et al., 2022 (Italy) [43] Not registered	60	VSL#3® (one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08) vs. Placebo	3 months	Lower TG, hs-CRP, transaminases, GGT, (AST)/alanine aminotransferase (ALT) ratio, and hepatic steatosis index (HSI). Non-significant decrease in fasting plasma glucose (FPG) in intervention group.
Chong et al., 2021 (UK) [32] ISRCTN05474560	Unknown	VSL#3® (one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08) vs. Placebo	10 weeks	Improved biomarkers related to cardiovascular risk.
Sepideh et al., 2015 (Iran) [26] IRCT: 2012122911920N1	42	Probiotic capsules (Lactobacillus casei 3 × 109 CFU/g, Lactobacillus acidophilus 3 × 1010 CFU/g, Lactobacillus rhamnosus 7 × 109 CFU/g, Lactobacillus bulgaricus 5 × 108 CFU/g, Bifidobacterium breve 2 × 1010 CFU/g, Bifidobacterium longum 1 × 109 CFU/g, and Streptococcus thermophilus 3 × 108 CFU/g) vs. Placebo	8 weeks	Lower insulin, insulin resistance, TNF-a, and IL-6.
Mitrovic et al., 2024 (Serbia) [41] Not registered	84	Synbiotic (Lactobacillus acidophilus CBT LA1 (16 × 109), Lactobacillus casei CBT LC5 (16 × 109) and Bifidobacterium lactis CBT BL3 (32 × 109) with 6.4 g of inulin) vs. Placebo	12 weeks	Reduced steatosis, hs-CRP.
Abhari et al., 2020 (Iran) [27] IRCT20100524004010N23	45	Synbiotic (B. coagulans and inulin) vs. Placebo	12 weeks	Lower ALT, GGT, TNF-α, nuclear factor-kB activity. Non-significant Glu decrease.
Eslamparast et al., 2014 (Iran) [28] NCT01791959	52	Synbiotic (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum, and Lactobacillus bulgaricus) and prebiotic (fructooligosaccharide) and probiotic cultures [magnesium stearate (source: mineral and vegetable) and a vegetable capsule (hydroxypropyl methyl cellulose)] vs. Placebo	28 weeks	Reduced ALT, AST, GGT, hs-CRP, TNF-α, and fibrosis score.
Bakhshimoghaddam et al., 2018 (Iran) [29] IRCT2017020932417N2	102	Synbiotic yogurt (Bifidobacterium animalis/mL and 1.5 g inulin) vs. Control	24 weeks	Lower NAFLD grade, ALT, AST, GGT, and alkaline phosphatase. Non-significant Glu decrease.
Javadi et al., 2018 (Iran) [22] IRCT201301223140N6	75	Probiotics (Bifidobacterium longum (B.L) and Lactobacillus acidophilus (L.A), Prebiotics, Combo	3 months	Lower ALT, AST, hs-CRP, TNF-a, and TAC with the combination of pro- and prebiotics.
Crommen et al., 2022 (Germany) [36] NCT03585413	60	Probiotics (Lactobacillus acidophilus, Bifidobacterium breve, B. longum, L. delbrueckii susp. bulgaricus, L. helveticus, L. plantarum, L. rhamnosus, L. casei, Lactococcus lactis susp. lactis, and Streptococcus thermophiles) + Micronutrients vs. Control	12 weeks	Better NAFLD fibrosis score, TG, and the visceral adiposity index. Changes in the HbA1c concentrations did not differ between groups after 12 wk. Fasting glucose, insulin concentrations, and HOMA-IR were not affected by either supplementation protocol.
Asgharian et al., 2016 (Iran) [30] IRCT2013122811763N15	80	Synbiotic capsules (Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophilus) vs. Placebo	8 weeks	Lower steatosis grade with synbiotic treatment.
Alam et al., 2022 (Bangladesh) [39] No. BSMMU/2017/12512	85	Probiotics (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum, and Lactobacillus bulgaricus) vs. Placebo with adjunct dietary modifications	6 months	Significant improvement in liver function and reduced ALT, AST, and inflammation markers. No effect of probiotics on the glucose levels of both obese and non-obese patients.

Table 1. Included studies.

Study	Sample	Intervention	Duration	Outcome
Escouto et al., 2023 (Brazil) [38] NCT02764047	8	Probiotics (Lactobacillus acidophilus Bifidobacterium lactis) vs. Placebo	6 months	Reduced AST to Platelet Ratio Index (APRI) score; no microbiota change. Glucose: no statistically significant differences between groups at the end of the study.
Behrouz et al., 2020 (Iran) [24] IRCT201410052394N13.	89	Probiotics (Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium longum, and Bifidobacterium breve), Prebiotics (Oligofructose; ORAFTI P95), Control	12 weeks	Lower ALT, AST, GGT in probiotic group. Lower TG, total cholesterol, ALT, AST, GGT in prebiotic group. No significant alterations in the levels of Glu.
Ahn et al., 2019 (Korea) [37] CT0001588	65	Probiotics (Lactobacillus acidophilus, L. rhamnosus, L. paracasei, Pediococcus pentosaceus, Bifidobacterium lactis, and B. breve) vs. Placebo	12 weeks	Reduced intrahepatic fat fraction (IHF), TG, Glu values did not change in either group.
Kobyliak et al., 2018 (Ukraine) [33] NCT03434860	58	Multi-probiotic (Lactobacillus + Lactococcus, Bifidobacterium, Propionibacterium, Acetobacter) vs. Placebo	8 weeks	Lower FLI, AST, GGT, TNF-α, IL-6.
Scorletti et al., 2022 (UK) [31] NCT01680640	104	Synbiotics (fructo-oligosaccharides (4 g/twice day) + Bifidobacterium animalis subsp. lactis BB-12) vs. Placebo	12 months	No liver fat change; weight loss linked with synbiotics. Glu: no statistically significant differences between groups at the end of the study.
Manzhalii et al., 2019 (Ukraine) [34] The trial was not registered in a publicly accessible database	75	Probiotic cocktail (Lactobacillus casei, L. rhamnosus, L. bulgaricus, Bifidobacterium longum, Streptococcus thermophilus and fructooligosaccharides (LBSF)) vs. Control	12 weeks	Lower ALT, stiffness; GGT unchanged. Decreased BMI and serum cholesterol levels, serum glucose remained constantly within the normal range between groups.
Mofidi et al., 2017 (Iran) [24] NCT02530138	50	Synbiotic (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum and Lactobacillus bulgaricus) and prebiotic (125 mg fructo-oligosaccharide) vs. Placebo	28 weeks	Reduced steatosis, inflammation, TAG.
Mohamad Nor et al., 2021 (Malaysia) [40] NCT04074889	39	Multi-strain probiotics (six different Lactobacillus and Bifidobacterium species) vs. Placebo	6 months	No change in steatosis and fibrosis; fasting glucose did not show any significant differences within both groups after the Intervention.
Mantri et al., 2024 (Germany) [35] The trial was pre-registered at Open Science Framework (https://osf.io/utsn4)	117	Synbiotic (Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, and Lactococcus lactis) vs. Placebo	7 weeks	Reduced ALT; alteration in microbiome composition.
Nabavi et al., 2014 (Iran) [25] Not registered	72	Probiotic yogurt (Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12) vs. Conventional	8 weeks	Lower ALT, AST, TC, LDL. Changes in serum. Glucose levels were not significant.
Duseja et al., 2019 (India) [44] No. CTRI/2008/091/000074	39	Probiotics (each capsule containing 112.5 billion live, lyophilised, lactic acid bacteria and bifidobacteria, namely Lactobacillus paracasei DSM 24733, Lactobacillus plantarum DSM 24730, Lactobacillus acidophilus DSM 24735, and Lactobacillus delbrueckii subsp. bulgaricus DSM 24734, Bifidobacterium longum DSM 24736, Bifidobacterium infantis DSM 24737, Bifidobacterium breve DSM 24732, and Streptococcus thermophilus DSM 24731) + Lifestyle mod.	1 year	Improved hepatocyte balloning, lobullar inflammation, NAS, ALT; lower TNF-α. No significant change in the HOMA-IR levels in both groups of patients at 3 and 12 months.
Aller et al., 2011 (Spain) [42] Not registered	30	Probiotics (Lactobacillus bulgaricus and Streptococcus thermophilus) vs. Placebo	3 months	Reduced ALT, AST, GGT.
Derosa et al., 2022 (Italy) [43] Not registered	60	VSL#3® (one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08) vs. Placebo	3 months	Lower TG, hs-CRP, transaminases, GGT, (AST)/alanine aminotransferase (ALT) ratio, and hepatic steatosis index (HSI). Non-significant decrease in fasting plasma glucose (FPG) in intervention group.
Chong et al., 2021 (UK) [32] ISRCTN05474560	Unknown	VSL#3® (one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08) vs. Placebo	10 weeks	Improved biomarkers related to cardiovascular risk.
Sepideh et al., 2015 (Iran) [26] IRCT: 2012122911920N1	42	Probiotic capsules (Lactobacillus casei 3 × 109 CFU/g, Lactobacillus acidophilus 3 × 1010 CFU/g, Lactobacillus rhamnosus 7 × 109 CFU/g, Lactobacillus bulgaricus 5 × 108 CFU/g, Bifidobacterium breve 2 × 1010 CFU/g, Bifidobacterium longum 1 × 109 CFU/g, and Streptococcus thermophilus 3 × 108 CFU/g) vs. Placebo	8 weeks	Lower insulin, insulin resistance, TNF-a, and IL-6.
Mitrovic et al., 2024 (Serbia) [41] Not registered	84	Synbiotic (Lactobacillus acidophilus CBT LA1 (16 × 109), Lactobacillus casei CBT LC5 (16 × 109) and Bifidobacterium lactis CBT BL3 (32 × 109) with 6.4 g of inulin) vs. Placebo	12 weeks	Reduced steatosis, hs-CRP.
Abhari et al., 2020 (Iran) [27] IRCT20100524004010N23	45	Synbiotic (B. coagulans and inulin) vs. Placebo	12 weeks	Lower ALT, GGT, TNF-α, nuclear factor-kB activity. Non-significant Glu decrease.
Eslamparast et al., 2014 (Iran) [28] NCT01791959	52	Synbiotic (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum, and Lactobacillus bulgaricus) and prebiotic (fructooligosaccharide) and probiotic cultures [magnesium stearate (source: mineral and vegetable) and a vegetable capsule (hydroxypropyl methyl cellulose)] vs. Placebo	28 weeks	Reduced ALT, AST, GGT, hs-CRP, TNF-α, and fibrosis score.
Bakhshimoghaddam et al., 2018 (Iran) [29] IRCT2017020932417N2	102	Synbiotic yogurt (Bifidobacterium animalis/mL and 1.5 g inulin) vs. Control	24 weeks	Lower NAFLD grade, ALT, AST, GGT, and alkaline phosphatase. Non-significant Glu decrease.
Javadi et al., 2018 (Iran) [22] IRCT201301223140N6	75	Probiotics (Bifidobacterium longum (B.L) and Lactobacillus acidophilus (L.A), Prebiotics, Combo	3 months	Lower ALT, AST, hs-CRP, TNF-a, and TAC with the combination of pro- and prebiotics.
Crommen et al., 2022 (Germany) [36] NCT03585413	60	Probiotics (Lactobacillus acidophilus, Bifidobacterium breve, B. longum, L. delbrueckii susp. bulgaricus, L. helveticus, L. plantarum, L. rhamnosus, L. casei, Lactococcus lactis susp. lactis, and Streptococcus thermophiles) + Micronutrients vs. Control	12 weeks	Better NAFLD fibrosis score, TG, and the visceral adiposity index. Changes in the HbA1c concentrations did not differ between groups after 12 wk. Fasting glucose, insulin concentrations, and HOMA-IR were not affected by either supplementation protocol.
Asgharian et al., 2016 (Iran) [30] IRCT2013122811763N15	80	Synbiotic capsules (Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophilus) vs. Placebo	8 weeks	Lower steatosis grade with synbiotic treatment.
Alam et al., 2022 (Bangladesh) [39] No. BSMMU/2017/12512	85	Probiotics (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium longum, and Lactobacillus bulgaricus) vs. Placebo with adjunct dietary modifications	6 months	Significant improvement in liver function and reduced ALT, AST, and inflammation markers. No effect of probiotics on the glucose levels of both obese and non-obese patients.

Table 2. Risk of bias of included studies.

Study	Selection Bias	Performance Bias	Attrition Bias	Detection Bias
Escouto et al., 2023/Brazil [38]	Low risk	Low risk	Low risk	Unclear/unknown risk
Behrouz et al., 2020/Iran [24]	Low risk	Low risk	Low risk	Low risk
Ahn et al., 2019/Korea [37]	Low risk	Low risk	Low risk	Low risk
Kobyliak et al., 2018/Ukraine [33]	Low risk	Low risk	Low risk	Low risk
Scorletti et al., 2022/UK [31]	Low risk	Low risk	Low risk	Low risk
Alam et al., 2022/Bangladesh [39]	High risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Manzhalii et al., 2019/Ukraine [34]	High risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Mofidi et al., 2017/Iran [24]	Unclear/unknown risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Mohamad Nor et al., 2021/Malaysia [40]	Low risk	Low risk	Low risk	Low risk
Mantri et al., 2024/Germany [35]	Low risk	Low risk	Low risk	Low risk
Nabavi et al., 2014/Iran [25]	Low risk	Low risk	Low risk	Low risk
Scorletti et al., 2020/UK [31]	Low risk	Low risk	Low risk	Low risk
Sepideh et al., 2015/Iran [26]	Low risk	Low risk	Low risk	Low risk
Mitrovic et al., 2024/Serbia [41]	Low risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Abhari et al., 2020/Iran [27]	Low risk	Low risk	Low risk	Low risk
Eslamparast et al., 2014/Iran [28]	Low risk	Low risk	Low risk	Low risk
Bakhshimoghaddam et al., 2018/Iran [29]	Low risk	Unclear/unknown risk	Low risk	Low risk
Aller et al., 2011/Spain [42]	Low risk	Low risk	Low risk	Low risk
Javadi et al., 2018/Iran [22]	Low risk	Low risk	Low risk	Low risk
Crommen et al., 2022/Germany [36]	Low risk	Low risk	Low risk	Low risk
Derosa et al., 2022/Italy [43]	Low risk	Low risk	Low risk	Low risk
Asgharian et al., 2016/Iran [30]	Low risk	Low risk	Low risk	Low risk
Chong et al., 2021/UK [32]	Low risk	Low risk	Low risk	Low risk
Duseja et al., 2019/India [44]	Low risk	Low risk	Low risk	Low risk

Table 2. Risk of bias of included studies.

Study	Selection Bias	Performance Bias	Attrition Bias	Detection Bias
Escouto et al., 2023/Brazil [38]	Low risk	Low risk	Low risk	Unclear/unknown risk
Behrouz et al., 2020/Iran [24]	Low risk	Low risk	Low risk	Low risk
Ahn et al., 2019/Korea [37]	Low risk	Low risk	Low risk	Low risk
Kobyliak et al., 2018/Ukraine [33]	Low risk	Low risk	Low risk	Low risk
Scorletti et al., 2022/UK [31]	Low risk	Low risk	Low risk	Low risk
Alam et al., 2022/Bangladesh [39]	High risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Manzhalii et al., 2019/Ukraine [34]	High risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Mofidi et al., 2017/Iran [24]	Unclear/unknown risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Mohamad Nor et al., 2021/Malaysia [40]	Low risk	Low risk	Low risk	Low risk
Mantri et al., 2024/Germany [35]	Low risk	Low risk	Low risk	Low risk
Nabavi et al., 2014/Iran [25]	Low risk	Low risk	Low risk	Low risk
Scorletti et al., 2020/UK [31]	Low risk	Low risk	Low risk	Low risk
Sepideh et al., 2015/Iran [26]	Low risk	Low risk	Low risk	Low risk
Mitrovic et al., 2024/Serbia [41]	Low risk	Unclear/unknown risk	Low risk	Unclear/unknown risk
Abhari et al., 2020/Iran [27]	Low risk	Low risk	Low risk	Low risk
Eslamparast et al., 2014/Iran [28]	Low risk	Low risk	Low risk	Low risk
Bakhshimoghaddam et al., 2018/Iran [29]	Low risk	Unclear/unknown risk	Low risk	Low risk
Aller et al., 2011/Spain [42]	Low risk	Low risk	Low risk	Low risk
Javadi et al., 2018/Iran [22]	Low risk	Low risk	Low risk	Low risk
Crommen et al., 2022/Germany [36]	Low risk	Low risk	Low risk	Low risk
Derosa et al., 2022/Italy [43]	Low risk	Low risk	Low risk	Low risk
Asgharian et al., 2016/Iran [30]	Low risk	Low risk	Low risk	Low risk
Chong et al., 2021/UK [32]	Low risk	Low risk	Low risk	Low risk
Duseja et al., 2019/India [44]	Low risk	Low risk	Low risk	Low risk

3.5. Probiotics, Prebiotics, and Synbiotics

The strains most frequently utilized in the studies included in this scoping review consist of Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium longum, and Streptococcus thermophilus. These strains are commonly found in both probiotic capsules and synbiotic products, often paired with prebiotics such as inulin or fructooligosaccharides to improve their effectiveness. Additionally, Lactobacillus casei and Lactobacillus bulgaricus are regularly referenced, especially in yogurt-based products.

3.6. Hepatic Steatosis and Fibrosis Markers

Nine studies examined the impact of probiotics on markers of hepatic steatosis and fibrosis. According to Escouto et al. [38], there were no statistically significant differences in liver fibrosis and steatosis activity between the intervention group and the placebo group. Similarly, Mohamad Nor et al. [40] indicated that there were no significant changes in hepatic steatosis and fibrosis levels by the end of their study. In the research conducted by Ahn et al. [37], the mean intrahepatic fat (IHF) fraction decreased after 12 weeks of treatment in the probiotic group compared to baseline, while the placebo group showed no reduction. Manzhalii et al. [34] found that liver stiffness was decreased in the probiotic-treated group compared to the control group. Additionally, Kobyliak et al. [33] reported that the multiprobiotic “Symbiter” administered to the intervention group led to a significant decrease in the fatty liver index (FLI), with no change observed in the placebo group. Similarly, Crommen et al. [36] observed that Pro + SM enhanced the NAFLD fibrosis score and the visceral adiposity index in contrast to Con + BM. Additionally, Derosa et al. [43] reported a significant reduction in the hepatic steatosis index (HSI) within the VSL#3^® group. Duseja et al. [44] noted that at the one-year mark, there were significant improvements in hepatocyte ballooning, lobular inflammation, and NAS score in the probiotic group compared to baseline. Furthermore, Javadi et al. [22] indicated that the fatty liver grade in both the probiotic and prebiotic plus probiotic groups decreased relative to the placebo group.

Eight studies investigated the impact of synbiotics on liver steatosis. In the research conducted by Bakhshimoghaddam et al. [29], a notable reduction in the grades of NAFLD was observed in the synbiotic group when compared to the control groups. Another study revealed that both the intervention and control groups experienced reductions in hepatic steatosis and fibrosis; however, the synbiotic group showed a significantly greater mean reduction than the placebo group [24]. Similarly, Mitrovic et al. [41] reported a significant decrease in liver steatosis following 12 weeks of synbiotic use. Abhari et al. [27] also found a significant reduction in hepatic steatosis within the synbiotic group compared to the placebo group. Furthermore, Asgharian et al. [30] noted a significant decrease in ultrasound grades from baseline in the synbiotic group, while no significant changes were detected in the control group. Conversely, in the RCT by Scorletti et al. [31], no significant difference in liver fat reduction was found between the intervention and control groups after the synbiotic treatment.

3.7. Hepatic Function

Eight studies assessed the effects of probiotics on liver function. Escouto et al. [38] reported that the primary outcome, measured using the AST to Platelet Ratio Index (APRI), decreased over time in the intervention group. Similarly, Kobyliak et al. [33] found that probiotics reduced serum aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) levels. Manzhalii et al. [34] demonstrated that a 12-week probiotic treatment significantly lowered serum ALT by over 20% compared to the control group, though the reduction in GGT was not significant. Nabavi et al. [25] observed that probiotic yogurt consumption was associated with reduced serum alanine aminotransferase (ALT) and AST levels. Aller et al. [42] also noted decreases in ALT, AST, and GGT levels, whereas liver function parameters remained stable in the control group.

Crommen et al. [36] found no significant differences in serum ALT levels between groups, while Pro + SM showed improvements in serum AST compared to Con + BM. Derosa et al. [43] reported significant reductions in transaminases and GGT in the VSL#3^® group compared to the placebo group, with the AST-to-ALT ratio notably lower in the VSL#3^® group. Lastly, Duseja et al. [44] observed a substantial improvement in ALT levels in the probiotic group after one year compared to the placebo.

Five studies evaluated the impact of synbiotics on liver function. In the research conducted by Bakhshimoghaddam et al. [29], there were notable reductions in serum levels of ALT, AST, alkaline phosphatase, and GGT across the synbiotic, conventional, and control groups. Similarly, Mantri et al. [35] reported that a 7-week intervention with synbiotics led to decreased ALT levels, particularly among participants with higher body fat percentages, likely due to changes in the gut microbiome. Furthermore, Abhari et al. [27] observed significant decreases in serum ALT and γ-GT in the synbiotic group compared to the placebo group. Eslamparast et al. [28] also noted significant alterations in ALT and AST levels in the synbiotic group relative to the control group. In contrast, Asgharian et al. [30] reported no association between synbiotic supplementation and changes in ALT or AST levels.

Two studies examined how probiotic and prebiotic interventions impact liver function. According to Behrouz et al. [23], levels of ALT, AST, GGT, and alkaline phosphatase were reduced in comparison to the control group. Similarly, Javadi et al. [22] reported that ALT and AST levels were lower in the intervention groups when compared to the placebo group.

3.8. Lipid Profiles

Three studies examining probiotics within the intervention group analyzed levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). Nabavi et al. [25] discovered that consuming probiotic yogurt led to reductions in total cholesterol and low-density lipoprotein cholesterol when compared to the control group. Similarly, Ahn et al. [38] found a greater decrease in TG in the probiotic treatment group compared to the placebo group. Manzhalii et al. [34] noted a more pronounced reduction in serum TC among those receiving probiotics versus the control group. Derosa et al. [43], however, found no significant changes in TC, LDL-C, HDL-C, or adiponectin (ADN) levels in either treatment group. Nonetheless, a statistically significant reduction in triglycerides was observed in the group receiving VSL#3^® compared to the placebo group. A study examining a synbiotic supplement assessed its impact on LDL-c, HDL-c, TC, and TG levels. According to Mofidi et al. [24], the TAG levels were notably lower in the group receiving the synbiotic compared to the placebo group.

3.9. Inflammation Markers

Four studies examined the impact of probiotics on inflammation markers. Kobyliak et al. [33] reported that, among markers of chronic systemic inflammation, only tumor necrosis factor (TNF) and IL-6 levels showed significant reductions following probiotic supplementation. Similarly, Sepideh et al. [26] found that TNF and IL-6 levels significantly decreased in the probiotic group by the end of the study. Derosa et al. [43] observed lower levels of high-sensitivity C-reactive protein (hs-CRP) in patients treated with VSL#3^® compared to the placebo group. Additionally, Duseja et al. [44] noted a significant reduction in TNF and endotoxin levels in the probiotic group compared to the placebo group after one year.

Two studies explored how probiotic and prebiotic supplementation affects inflammation markers. In the research conducted by Javadi et al. [22], significant differences were observed in the means of hs-CRP, TNF, and TAC among the four groups. The combination of pro- and prebiotics led to a notable reduction in hs-CRP levels compared to the placebo, as well as the probiotic and prebiotic groups. At the end of the study, the mean TNF levels in the probiotic, prebiotic, and combined probiotic plus prebiotic groups were significantly lower than in the placebo group. Similarly, Behrouz et al. [23] reported a significant decrease in high-sensitive C-reactive protein across all groups.

Four studies examined how synbiotic supplementation impacts inflammation markers. In the research conducted by Mofidi et al. [24] a reduction in most inflammatory mediators was observed in the group receiving synbiotics compared to those in the placebo group. According to Mitrovic et al. [41], patients who were treated with synbiotics exhibited a notable decrease in the levels of hsCRP. Abhari et al. [27] reported that synbiotic supplementation led to a significant reduction in serum TNF and activity of nuclear factor-kB. Additionally, Eslamparast et al. [28] found significant decreases in hsCRP and TNF within the synbiotic group.

3.10. Glucose Homeostasis

Across the included studies, the impact of probiotic, prebiotic, and synbiotic interventions on glucose homeostasis was generally limited. Most trials, including those by Ahn et al. [37], Escouto et al. [38], and Mohamad Nor et al. [40], reported no significant changes in fasting glucose. A few studies noted non-significant downward trends while the study of Sepideh et al. [26] showed a reduction in insulin resistance markers. Overall, the findings suggest that while these interventions may support metabolic health, their isolated effect on glycemic control in MASLD remains modest and inconsistent.

4. Discussion

This scoping review emphasizes the therapeutic promise of probiotics, prebiotics, and synbiotics for managing and treating MASLD, as demonstrated by the supporting literature. The gut–liver axis, essential to the pathophysiology of MASLD, highlights how dysbiosis and gut permeability contribute to the progression of liver disease. It seems that probiotics, prebiotics, and synbiotics can influence these elements, affecting hepatic steatosis, inflammation, and liver function.

Most of the studies featured in the review showed a notable positive impact from the intervention of probiotics on the indicators of hepatic steatosis and fibrosis. In line with this, Carpi et al. [46] noted that employing probiotics, prebiotics, and synbiotics is viewed as a potential and encouraging approach to manage gut microbiota and yields positive outcomes for individuals with liver diseases. The clinical trials referenced in this study illustrated that interventions targeting gut microbiota could enhance liver health by reducing hepatic enzymes along with steatosis and fibrosis.

The use of probiotics, prebiotics, and synbiotics has shown significant improvements in liver enzymes, including ALT, AST, and GGT, aligning with evidence from other systematic reviews and meta-analyses. Tang et al. [47] conducted a comprehensive analysis demonstrating that probiotic treatment reduced ALT and AST levels by 7.22 U/L each, ALP by 25.87 U/L, and GGT by 5.76 U/L. Another meta-analysis highlighted notable decreases in ALT, AST, and TC within the probiotic group compared to controls [48]. Similarly, Ma et al. [49] confirmed substantial reductions in ALT and AST levels with probiotic supplementation.

Xiao et al. [50] further revealed significant benefits of probiotic therapy on body mass index (WMD: −1.46, 95% CI: [−2.44, −0.48]), ALT (WMD: −13.40, 95% CI: [−17.03, −9.77]), AST (WMD: −13.54, 95% CI: [−17.86, −9.22]), and GGT (WMD: −9.88, 95% CI: [−17.77, −1.99]). Additionally, Zhou et al. [51] demonstrated that probiotic treatments lasting 12 weeks or more led to improvements in ALT, GGT, TG, and blood glucose levels.

In this scoping review, we observed a notable improvement in the lipid profile of patients with MASLD who underwent probiotic treatment. In line with this, Tang et al. [47] reported significant reductions in TC, LDL cholesterol, and TG following probiotic intervention. Additionally, the meta-analysis conducted by Gao et al. [52] identified statistical variations in TC, HDL, and TG levels between the probiotics and control groups across diverse patient populations. Furthermore, Ma et al. [49] revealed that probiotic therapy led to a significant decrease in TC and HDL. However, this meta-analysis indicated that probiotics did not correlate with changes in LDL. Conversely, Xiao et al. [48] found that probiotic therapy did not yield positive effects on lipid profiles.

Additionally, we demonstrated that the intervention with probiotics led to significant improvements in inflammation markers within the studies analyzed. Conversely, the systematic reviews and meta-analyses conducted by Yang et al. [48] and Xiao et al. [50] concluded that there was no association between probiotic therapy and changes in TNF. In Zhou et al.’s meta-analysis [51], the findings indicated that probiotic intervention did not result in significant enhancements of inflammatory factors. However, the clinical trials reviewed in Carpi et al.’s study [46] showed that interventions targeting gut microbiota could positively affect various inflammation markers. Furthermore, Ma et al. [49] reported that the intervention group receiving probiotic therapy experienced a significant reduction in TNF compared to the placebo group. In Zhou et al.’s meta-analysis [51], the results again indicated that probiotic intervention did not meaningfully improve inflammatory factors.

A comparative analysis of the probiotic and synbiotic formulations used across the 24 RCTs reveals that while certain strains, such as Lactobacillus, Bifidobacterium, and Streptococcus, were commonly employed, their clinical outcomes varied based on combination, dosage, and duration. For instance, studies using the VSL#3^® formulation consistently reported improvements in liver enzymes (ALT, AST), hepatic steatosis index, and inflammatory markers such as hs-CRP and TNF-a. In contrast, trials using more basic formulations (e.g., probiotic yogurt) showed modest benefits in lipid profiles but limited effects on glucose or liver stiffness.

Synbiotic combinations that included fructooligosaccharides generally led to greater reductions in hepatic steatosis and systemic inflammation compared to probiotic-only interventions. However, not all synbiotic studies showed consistent results. In one study, despite using Bifidobacterium animalis subsp. Lactis BB-12 with prebiotics, the authors observed no significant changes in liver fat content, suggesting that strain specificity and host factors (e.g., diet, microbiota baseline composition) critically influence outcomes.

Moreover, combinations that included Lactobacillus casei and Bifidobacterium longum were more effective in improving both biochemical markers and imaging-based outcomes, reinforcing the potential role of multi-strain formulations. In summary, while overlapping bacterial species were present in many formulations, therapeutic responses differed—likely due to heterogeneity in strain synergy, dosages, intervention duration, and patient profiles.

Emerging research subsists strong connection between gut microbiota and muscle health, particularly in the context of sarcopenia. Meta-analyses of randomized controlled trials have reported that probiotics may positively influence muscle mass, inflammation and mitochondrial activity, particularly in older adults or patients with liver disease. While not directly assessed in MASLD-focused studies, these findings warrant further exploration of probiotic therapies in patients with coexisting sarcopenia and metabolic liver dysfunction [53,54].

Recent meta-analyses and clinical trials provide growing evidence that probiotics, prebiotics, and synbiotics can positively influence patients with chronic kidney disease (CKD) by reducing systemic inflammation, improving uremic toxin clearance, and then chancing gut integrity [55,56]. Similarly, in patients with cirrhosis and portal hypertension, interventions targeting the gut–liver axis have shown promise in modulating endotoxemia and vascular resistance [57,58]. These findings support the broader utility of microbiota-targeted therapies in systemic diseases involving liver and kidney function.

Study Limitations

This review provides a novel synthesis of the therapeutic effects of probiotics, prebiotics, and synbiotics on MASLD, emphasizing their role in modulating the gut–liver axis but there are several limitations that should be considered. There is a notable variability in the study designs, the specific probiotic strains used in the intervention groups, and the lengths of the included studies. Additionally, the dosages of probiotics varied significantly across the studies. The absence of standardized protocols for probiotic interventions represents a major limitation and may lead to differences in outcomes as well as may affect the generalization of the findings.

Another limitation of the findings is the relatively small sample sizes of the studies included, which affects their statistical power. Although most of the studies showed significant improvements in the parameters of MASLD, a few did not reach significant results due to the small sample sizes. Consequently, this limits our capacity to make conclusive recommendations about the clinical effectiveness of probiotic supplements for treating MASLD.

Additionally, the length of the studies was generally brief, typically lasting from 8 weeks to a few months. This absence of extended studies restricts the impact of probiotic strains on the treatment of MASLD, as MASLD is a chronic condition that necessitates long-term interventions.

Another limitation of the study lies in its geographical focus, as most of the included research was conducted in Iran and other parts of Asia. These regions have distinct dietary patterns that may influence microbiota composition, differing significantly from those observed in European populations. Consequently, this regional specificity raises concerns about the global applicability of the findings, as variations in microbiota across populations could impact the effectiveness of probiotic interventions.

In conclusion, several of the studies reviewed failed to mention potential confounding variables such as medication usage or initial microbiota composition that could have affected their results.

5. Conclusions

In summary, this scoping review provides valuable insights into the benefits of probiotics on MASLD treatment. Future clinical trials should prioritize the development of standardized protocols for probiotic, prebiotic, and synbiotic interventions. This includes selecting strains with proven efficacy as well as ensuring consistency in dosages. Given the chronic progression of MASLD, future studies should incorporate extended follow-up periods, potentially spanning over several years. Such designs will provide critical insights into the long-term efficacy and safety of gut microbiota modulating interventions. The integration of probiotics, prebiotics, and synbiotics into clinical practice requires alignment with existing MASLD guidelines. Recommendations for incorporating these interventions into treatment plans, alongside dietary lifestyle modifications, can enhance patient outcomes.