Gut-liver axis: Clinical trial suggests novel and sustainable approach to manage fatty liver diseases

08 Sep 2023 --- International researchers suggest that daily intake of resistant starch – a non-digestible fiber – may help manage non-alcoholic fatty liver disease (NAFLD) by altering gut bacteria composition, lowering liver triglycerides and liver enzymes associated with liver injury and inflammation.

For four months, participants in a clinical trial consumed resistant starch – known to encourage the growth of beneficial gut bacteria – which reduced intrahepatic triglyceride content (IHTC) by 5.89% after adjusting for weight loss. IHTC accumulation can potentially lead to NAFLD. 

Moreover, supplementation decreased serum branched-chain amino acids (BCAAs) and gut microbial species, particularly Bacteroides stercoris, strongly linked to IHTC and liver enzymes.

“We identified a new dietary intervention for NAFLD, and the approach is effective, affordable and sustainable,” co-author professor Huating Li, from the Shanghai Sixth People’s Hospital, tells Nutrition Insight. 

“Compared with strenuous exercise or weight loss treatment, increasing resistant starch intake upon a normal and balanced diet is much easier for people to follow. We hope people can release the importance and effectiveness of lifestyle changes for disease management and put it into practice.”

New NAFLD intervention 
A fat buildup in the liver causes NAFLD and can lead to severe liver diseases. It affects about 30% of the global population and can contribute to other conditions, such as Type 2 diabetes, cardiovascular disease and chronic kidney disease. 

The consumption of resistant starch led to both weight loss (5.78%) and the reduction of liver triglycerides.There is no approved medicine to treat the disease. Doctors usually recommend dietary changes and exercise to alleviate the conditions. 

Professor Weiping Jia, co-author of the study, tells us that weight loss and resistant starch intake are effective dietary approaches to alleviating NAFLD. 

“Previous work has shown that weight loss is safe and dose-dependently improves histological disease activity in non-alcoholic steatohepatitis (the most severe form of NAFLD), with weight loss of 5% or more associated with NAFLD improvement and a weight loss equal to or less than 7% associated with histological improvement.” 

“In our study, it is worth noting that the consumption of resistant starch led to both weight loss (5.78%) and the reduction of liver triglycerides.” 

“More importantly, the effect of resistant starch in reducing liver triglycerides is independent of weight loss, with only 23% of liver fat reduction contributed by weight loss.”

Gut liver-axis 
The researchers note that evidence suggests that NAFLD is closely related to gut microbiota through the gut-liver axis. For example, patients in the early stages of the disease have an altered gut bacteria profile. Although microbiota-directed foods have shown promise in NAFLD patients, studies are in an early stage. 

In the current study, published in Cell Metabolism, 196 NAFLD patients followed a balanced dietary plan designed by a nutritionist. Over half of the participants (99) received a resistant starch powder derived from maize, while the control group consumed calorie-matched, non-resistant corn starch. 

Trial participants drank 20 g of the starch mixed with 300 mL water before meals twice daily over four months. 

“After the four-month resistant starch intake, the relative reduction of the liver fat fraction was 39.4% compared to the control,” highlights Li. “In prior research, an equal to or less than 30% reduction has been associated with an improvement in histological steatohepatitis, a more severe disease stage and is one of the leading causes of cirrhosis and hepatocellular carcinoma.”  

In addition, liver enzymes and inflammatory factors were reduced for participants consuming resistant starch. 

Underlying mechanism 
A biomarker for NAFLD was significantly reduced after the consumption of resistant starch. 

“Our study not only demonstrates the clinical benefits of using resistant starch in NAFLD via a randomized controlled clinical trial but also reveals the underlying mechanism,” says Jia. 

“From a double-blinded clinical trial to the identification of key microbial species, and further to the causal relationship between microbiome (and its metabolites) and host phenotype, our study is comprehensive and provides a complete chain of evidence for research into microbiome-linked diseases.”

Currently, there is no approved medicine to treat NAFLD, doctors advise dietary changes and exercise.The resistant starch group had a different microbiota composition and functionality than the control group. For example, resistant starch reduced the abundance in the gut of B. stercoris, a species highly correlated with IHTC. 

The researchers note that these correlations remained significant even after controlling for obesity-related parameters, suggesting that resistant starch’s effect is independent of body weight. 

After transplanting fecal microbiota from resistant starch-treatment patients to mice eating a high-fat, high-cholesterol diet, liver weight and triglyceride levels were significantly reduced. In contrast, liver tissue grading improved compared to mice receiving microbiota from the control group. 

Next steps 
The researchers suggest that further research may reveal other possible molecular mechanisms by which the resistant starch-altered metabolites or gut microbes lead to the accumulation or reduction of liver fat, inflammation and fibrosis in the liver.

“Confirming histological responses would need liver biopsy in further studies,” notes Li. 

Jia adds that liver biopsy is invasive but is the gold standard for disease diagnosis. “In addition, a standardized diet can be used to directly control for the effect of diet as a potential confounding factor.”

Earlier research found benefits for patients with NAFLD from coffee consumption, while the link between vitamin A and the disease warrants more research. 

By Jolanda van Hal