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Probiotics in Nonalcoholic Fatty Liver Disease (NAFLD) - Prevention and Management

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The gut microbiome is closely linked to the development of NAFLD. In NAFLD cases, probiotic therapy regulates liver function, insulin, and lipid levels.

Medically reviewed by

Dr. Ghulam Fareed

Published At May 20, 2024
Reviewed AtMay 20, 2024


NAFLD, once considered a disorder primarily linked to alcohol consumption, is now recognized as a growing concern globally, surpassing other causes of chronic liver disease. It involves NAFL and NASH, with the latter often progressing to cirrhosis or liver cancer. While the precise pathogenesis remains complex, metabolic abnormalities like insulin resistance and obesity play central roles. The gut microbiota, crucial for overall health, influences NAFLD through the gut-liver axis, where the liver’s immune functions are closely tied to gut health.

Dysbiosis and microbial metabolic dysfunction are common in NAFLD patients, affecting liver health. This imbalance disrupts intestinal homeostasis, leading to immune disturbances and liver diseases. Currently, treatment primarily involves lifestyle modifications, as pharmaceutical options have limitations. Probiotics, beneficial microorganisms, promise NAFLD management by restoring gut microbiota balance and improving risk factors. Clinical trials support their potential therapeutic role, providing a foundation for evidence-based treatment strategies.

What Is Nonalcoholic Fatty Liver Disease (NAFLD)?

Nonalcoholic Fatty Liver Disease (NAFLD) is a prevalent chronic liver condition that typically results from nonalcoholic or drug-induced fat buildup in liver cells, known as hepatocyte steatosis. Globally, it affects roughly 25 percent of the population. Initially asymptomatic, NAFLD’s onset is gradual, potentially progressing to more severe stages like steatohepatitis, liver fibrosis, cirrhosis, and liver cancer without timely intervention. Alarmingly, it is also a leading cause of liver disease among children. The rising incidence, driven by shifting social lifestyles, poses a significant public health challenge.

How Is Gut Microbiota in NAFLD?

The growing body of research highlights the significant impact of gut microbiota dysbiosis on metabolic processes and immune responses, contributing to conditions such as obesity, metabolic syndrome, and NAFLD. Studies have shown that patients with NAFLD often exhibit increased gut permeability and bacterial overgrowth, particularly in those with more severe steatosis. Symbiosis is characterized by changes in bacterial composition, with enrichment in Proteobacteria, Enterobacteriaceae, Lachnospiraceae, Escherichia, and Bacteroidetes.

Notably, the ratio between Bacteroidetes and Firmicutes appears to be altered in NAFLD patients, with some studies indicating an increase in Bacteroidetes and a decrease in Firmicutes, while others show conflicting results. Furthermore, certain bacterial species, such as Escherichia coli, have been implicated in ethanol production, contributing to liver inflammation and oxidative stress in NASH.

Recent research suggests that gut microbiota composition may serve as a biomarker for the severity of fibrosis in NAFLD patients, with advanced fibrosis associated with an increase in Proteobacteria and E. coli. Similarly, cirrhotic patients exhibit an alteration in microbial diversity, with a decrease in Bacteroidetes and an increase in Proteobacteria and Fusobacteria.

Can Probiotics Help Treat or Prevent Nonalcoholic Fatty Liver Disease (NAFLD)?

Current interventions for managing NAFLD primarily focus on dietary and lifestyle changes, but patient compliance with these measures is often poor, leading to discouraging results. While hypolipidemic drugs, anti-TNFα agents, antioxidants, and diabetes medications have been proposed for NAFLD/NASH, no pharmacological therapies or surgical procedures have been approved for treatment.

In recent years, considerable efforts have been made to develop new strategies targeting the gut-liver axis, which has the potential to prevent NAFLD onset and progression. These approaches include untargeted methods like dietary modifications, probiotics, prebiotics, antibiotics, and fecal microbiota transplant (FMT), as well as microbiota-targeted therapy (MTT) aimed at selectively altering microbial and host metabolites.

Although the precise mechanisms by which gut dysbiosis contributes to liver pathology remain uncertain, promising results have been reported in preclinical and human studies investigating the modulation of intestinal flora. Probiotics, defined as live microorganisms that confer health benefits when administered adequately, have garnered increasing attention as a potential treatment for NAFLD.

Criteria for selecting probiotic strains include safety, functionality, and technological usability. Commercialized strains like Streptococcus, Lactobacillus, and Bifidobacteria have been shown to promote an anti-inflammatory environment, support intestinal epithelial growth and survival, and modulate the immune system and host defense against pathogenic bacteria.

Over the years, experimental models of NAFLD have yielded promising insights into microbiome therapeutics, paving the way for clinical evaluations of probiotics to mitigate the development and progression of NAFLD.

Combination probiotic therapies have shown even more promising outcomes in randomized trials. Famouri et al. conducted a triple-blind trial involving 64 obese children with sonographic NAFLD, administering a probiotic capsule containing multiple strains for 12 weeks. This group demonstrated significant reductions in ALT, lipid profile, and intrahepatic fat content compared to the placebo group. In another study, NAFLD patients treated with a multi-probiotic cocktail saw improvements in hepatic steatosis, aminotransferase activity, and inflammatory markers.

Meta-analyses have further supported the efficacy of probiotics in reducing hepatic fat content, improving lipid profiles, and enhancing insulin sensitivity in NAFLD/NASH patients. Additionally, probiotics have shown benefits in cirrhotic patients, improving gut microbiome composition, reducing endotoxemia and inflammation, and even enhancing cognitive function.

Though research on probiotic therapy for HCC is limited, preoperative and postoperative probiotic supplementation in HCC patients undergoing hepatic resection has been associated with improved liver function and reduced complications.

How Do Probiotics Help Manage Nonalcoholic Fatty Liver Disease?

The World Health Organization defines probiotics as "live microorganisms which, when administered in adequate amounts, confer a health benefit to the host." Probiotics have gained popularity as a means of disease prevention and promoting well-being. While their efficacy has been demonstrated in only a few diseases, probiotics are increasingly being explored for their potential therapeutic benefits.

Studies focusing on nonalcoholic fatty liver disease (NAFLD) have investigated various combinations of probiotics, most commonly including Bifidobacteria and Lactobacilli, for their effects on liver health. For example, Loguercio et al. and Li et al. reported improved liver function parameters with probiotic treatment. Loguercio et al. found that NAFLD patients treated with a mixed-species probiotic containing Bifidobacterium and Lactobacillus showed reduced serum alanine aminotransferase activity (ALT) and decreased markers of oxidative stress and inflammation. Li et al., in a study using genetically obese mice fed a high-fat diet, observed similar improvements in hepatic histology and insulin resistance with probiotic treatment comparable to anti-TNF antibodies.

Among the probiotic formulations studied, VSL #3, a combination of eight bacterial species, has been extensively investigated in NAFLD and NASH patients. Wong et al. administered a probiotic and prebiotic formula containing five bacterial species and prebiotics to NASH patients for six months. They found a reduction in intrahepatic triglyceride content and AST levels in the probiotic group, along with changes in microbiota composition favoring Bacteroidetes over Firmicutes abundance, which correlated with reduced intrahepatic triglycerides.

Meta-analyses of clinical trials investigating probiotics for NAFLD and NASH patients have shown statistically significant improvements in metabolic and inflammatory parameters compared to placebo, supporting the potential use of probiotics as a treatment option for these conditions.


Dysbiosis of the gut, characterized by an imbalance in the microbiota composition, is recognized as a risk factor contributing to the development and progression of nonalcoholic fatty liver disease (NAFLD). The potential of probiotics to restore gut dysbiosis has spurred interest in exploring probiotic therapy as an alternative approach to NAFLD treatment. A study revealed that supplementation with probiotics significantly benefits patients with NAFLD. Furthermore, probiotic supplementation positively impacts lipid metabolism, reduces insulin resistance, modulates immune function, enhances liver function, and slows disease progression in NAFLD treatment.

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Dr. Ghulam Fareed
Dr. Ghulam Fareed

Medical Gastroenterology


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