Clinical bottom line
Modulation of the gut microbiome represents a promising adjunctive strategy in managing nonalcoholic fatty liver disease (NAFLD), also termed metabolic-associated steatotic liver disease (MASLD). Evidence suggests that interventions targeting gut microbial composition and function—such as probiotics, prebiotics, dietary components, and phytochemicals—may improve hepatic steatosis and metabolic parameters by influencing bile acid metabolism, inflammation, and gut barrier integrity. However, clinical data remain preliminary, with heterogeneity in study designs and patient populations. Gut microbiome modulation should currently be considered complementary to established lifestyle and pharmacologic therapies pending further validation (Benedé-Ubieto et al., 2024; He et al., 2024).
What the evidence shows
Benedé-Ubieto et al. (2024) review the critical role of gut homeostasis in MASLD pathogenesis, emphasizing how dysbiosis disrupts bile acid signaling and promotes hepatic inflammation. They highlight that restoring microbial balance may alleviate disease progression.
He et al. (2024) conducted a randomized controlled trial demonstrating that curcumin supplementation reduced hepatic fat content in patients with nonalcoholic simple fatty liver disease, an effect linked to modulation of gut microbiota-dependent bile acid metabolism.
Saeed et al. (2025) discuss emerging microbiome-centered therapies, including probiotics, synbiotics, and fecal microbiota transplantation, which show potential in improving liver enzymes and insulin resistance, though large-scale trials are needed.
Milosevic et al. (2019) provide a comprehensive overview of the gut-liver axis, detailing mechanisms by which microbial metabolites influence liver health and how microbiota modulation may serve as a therapeutic target.
Heshmati et al. (2021) summarize clinical and preclinical studies supporting gut microbiome modulation as a strategy to reduce hepatic steatosis and inflammation in NAFLD.
Caveats and uncertainty
Most clinical trials to date are small, short-term, and heterogeneous in interventions and endpoints.
The complexity of gut microbiota and interindividual variability challenge standardization of microbiome-targeted therapies.
Long-term safety and efficacy data for interventions such as fecal microbiota transplantation are lacking.
It remains unclear which patient subgroups derive the greatest benefit from microbiome modulation.
Microbiome changes may be secondary to lifestyle modifications, complicating attribution of effects.
How this may change practice
Clinicians should consider gut microbiome modulation as a complementary approach alongside diet, exercise, and pharmacotherapy in NAFLD management.
Incorporation of specific probiotics or phytochemicals like curcumin may be reasonable in selected patients, recognizing current evidence limitations.
Future integration of microbiome profiling could personalize therapy and monitor response.
Ongoing research will clarify optimal agents, dosing, and patient selection to maximize benefit.
Multidisciplinary collaboration including hepatologists, nutritionists, and microbiome specialists will enhance implementation.