Review article: can bugs be drugs? The potential of probiotics and prebiotics as treatment for non‐alcoholic fatty liver disease

Abstract

Summary Background Non‐alcoholic fatty liver disease (NAFLD) has become the most common chronic liver condition. A major current research effort is ongoing to find potential strategies to treat NAFLD‐non‐alcoholic steatohepatitis (NASH), with special attention to the gut microbiota. Multiple animal studies and pilot clinical trials are assessing different gut microbiota modulating strategies such as faecal microbiota transplantation, antibiotics, probiotics, prebiotics and synbiotics. Aim To review the role of microbiota in NAFLD‐NASH and determine whether pro‐ and prebiotics have potential as treatment Methods Information was obtained from critically reviewing literature on PubMed on targeting the gut microbiota in NAFLD. Search terms included NAFLD, NASH, non‐alcoholic fatty liver disease, steatohepatitis; combined with microbiome, microbiota, gut bacteria, probiotics and prebiotics. Results Animal studies and the first emerging studies in humans show promising results for both the common probiotics Lactobacillus, Bifidobacterium and Streptococci as for short chain fatty acid (SCFA) butyrate‐producing bacteria. Also, prebiotics have positive effects on different mechanisms underlying NAFLD‐NASH. Conclusions The most promising strategies thus far developed to alter the microbiome in NAFLD‐NASH are probiotics and prebiotics. However, pre‐ and probiotic treatment of NAFLD‐NASH is relatively new and still under development. Actual understanding of the involved mechanisms is lacking and changes in the intestinal microbiota composition after treatment are rarely measured. Furthermore, large clinical trials with comparative endpoints are unavailable. Personalised treatment based on metagenomics gut microbiota analysis will probably be part of the future diagnosis and treatment of NAFLD‐NASH.

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

“…To determine the mechanisms of the anti-steatosis and anti-fibrotic changes in the liver after visceral nerve blockade, we examined changes in tight junctions of the small intestine, intestinal bacterial flora and SCFAs, which are reportedly related to NAFLD and NASH development (Koopman et al, 2019;Rahman et al, 2016).…”

“…The etiology of the disease includes not only obesity and dyslipidemia but also impaired glucose tolerance, hypertension, insulin resistance, abnormal hormone secretion, genetic factors and gut-liver axis (Wiest et al, 2017;Tilg et al, 2020), and these factors have a complicated relationship (Drescher et al, 2019). The effect of the gut-liver axis has been focused on microbiota changes (Boursier et al, 2016;Hu et al, 2020), short-chain fatty acids (SCFAs) (De Vadder et al, 2014;Koopman et al, 2019) and tight junction (Miele et al, 2009;Gupta et al, 2020;Rahman et al, 2016), which are reportedly related to steatohepatitis, hepatic fibrosis (Loomba et al, 2017) and carcinogenesis (Yoshimoto et al, 2013) in NAFLD. However, as these factors are diverse and the pathologic network connecting these factors has not been elucidated, standard treatment methods for NAFLD have not been established.…”

Constant Light Exposure Alters Gut Microbiota and Promotes the Progression of Steatohepatitis in High Fat Diet Rats

“…However, changes in gut microbiota were not entirely consistent among studies (Kolodziejczyk et al, 2019). For example, among NAFLD individuals, an increase in Proteobacteria and Bacteroidetes has been reported (Boursier et al, 2016;Shen et al, 2017), while a reduction in Proteobacteria and Bacteroidetes was also observed (Shin et al, 2017;Koopman et al, 2019). Different ethnicities and living environments may help explain these discrepancies.…”

Molecular links between non-alcoholic fatty liver disease and hepatocellular carcinoma

“…SCFAs improve hepatic autophagy and gut barrier function, and reduce the permeability of bacterial toxins. These gut products can reduce pro-inflammatory pathways and insulin resistance, which are associated with the progression of chronic liver disease [78,79] . The gut microbiota composition is dynamic and may be influenced by diet, hygiene and the use of antibiotics [80] .…”