As obesity reaches epidemic numbers, our hard-working livers are suffering. This amazing organ is a multitasker par excellence: It detoxifies, builds proteins, and is crucial to metabolism. The burden of obesity complicates its job. And drugs and alcohol are no friends to our livers either.
Researchers have begun unravelling the relationship between gut microbiota and host metabolism in chronic liver diseases, most notably non-alcoholic fatty liver disease or NAFLD, which is the focus of this article.
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease numbers have soared right along with the obesity epidemic; global prevalence is 25%. It includes simple fatty liver (NAFL) and steatohepatitis (NASH) with possible fibrosis.
As its name indicates, NAFLD is marked by fat accumulation in liver cells, a manifestation of obesity and the metabolic syndrome. About 20% of patients with NAFLD develop NASH, inflammation that can progress to cirrhosis and liver cancer.
As close neighbors, gut microbes and the liver forge a symbiotic bond, stabilized with metabolic, immune, and neuroendocrine crosstalk. This bi-directional interface is called the gut-liver axis.
Dysbiosis and fatty liver
Several malfunctions can lead to gut dysbiosis. Obesity is a primary cause of gut- liver axis malfunction, allowing a deranged passage of bacterial components into circulation or so-called “leaky” gut. Increased intestinal permeability and bacterial translocation may allow microbial metabolites to reach the liver where they can inflame and disrupt. Gut dysbiosis may lead to NAFLD. Recent reviews report changes in gut-microbiota functioning in liver diseases. NAFLD and NASH patients have altered gut microbiomes. Interestingly, gut microbiome dysbiosis correlates closely to NAFLD severity and progression.
Pathways from dysbiosis to disease
Dysbiosis in the gut taints the normal gut–liver axis resulting in increased inflammation, steatosis, and fibrosis.
Inflammation: Intestinal dysbiosis spurs the translocation of bacterial products via a leaky gut to the bloodstream. Systemic and liver inflammation follows.
Steatosis: Dysbiosis can increase steatosis which is a fancy way of saying the buildup of fat in the liver. Dysbiosis increases fatty liver by changes in fat metabolism. In addition, steatosis results from overall increased short chain fatty acids (SCFA) production. This is tricky as not all SCFAs act the same. Remember, bacteria ferment fibers to spawn short chain fatty acids–mainly butyrate, propionate, and acetate. Acetate, produced by Bacteroidetes, is obesogenic whereas butyrate is anti-obesogenic and improves insulin sensitivity among other benefits. In dysbiosis of the gut, there are changes in the ratio of Bacteroidetes to Firmicutes, and increased acetate production. Yet another apparent pathway involves changes in bile acids due to disrupted gut microbes.
Fibrosis: Dysbiosis causes gut microbes to metabolize choline by an alternate route which disrupts glucose and fat metabolism; this in turn leads to hepatic inflammation, fibrosis, and steatosis.
Probiotics and NAFLD
If dysbiosis is a driver of liver disease, then reversing it may be one solution. As many studies have revealed, probiotics may restore normal gut flora. In doing so, gut walls are reinforced. A range of studies denotes that mucosal barrier function can be improved by probiotic treatment. But obviously not all probiotic species nor strains have the same impact on gut microbes. Probiotics may benefit the gut- liver axis not only though barrier function but also by impact on inflammation and metabolism.
Animals: Multiple experimental trials in animals have shown therapeutic effects of probiotics in NAFLD. Results varied, but improvement in liver enzymes, hepatic inflammation, hepatic steatosis, and hepatic fibrosis were seen.
Humans: Now scientists are testing whether probiotics may be beneficial in humans with NAFLD. An excellent 2019 review indicated that probiotics may indeed act in this capacity. The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD appeared in Diseases. The authors include trials along with specific probiotic strains in helpful charts. The available studies clearly show that probiotics have a positive effect on the various measures of NAFLD in patients. Numerous clinical studies (see chart) that assessed serum levels of common liver function tests (aspartate aminotransferase and alanine aminotransferase) demonstrated significant improvement with probiotic and synbiotic treatment. Numerous studies using probiotics showed good results when measuring other markers including steatosis and fibrosis. Role of Probiotics in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-analysis showed that a variety of parameters had significant improvement after probiotic treatment in different trials. However use of varying strains, dose patterns, and treatment duration clouded hopes for clinical protocols going forward. Importantly, no major adverse effects or safety issues were noted.
Future of probiotic therapy
Our knowledge about the clinical significance of probiotics’ use in liver disease is starting to take shape. However, questions remain. Which probiotic and which strain will meet the targets? Another confounder is that many of the studies included prebiotics which can act independently on liver disease.
Collectively, these clinical studies reinforced by prior animal research suggest a role for probiotics in a public health problem that is only getting bigger.
Note: The views and opinions expressed here are those of the author(s) and contributor(s) and do not necessarily reflect those of the publisher and editors of WholeFoods Magazine.
Clare Fleishman MS RD bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media and websites. From corporate whiteboards to refugee schools in Egypt, Fleishman agitates for personal and public change. In 2010, she launched www.ProbioticsNow.com to share the cascade of new discovery in the microbiome. Always amazed at this “forgotten organ” Fleishman also creates white papers, blogs, videos and social media for the International Probiotics Association.