"Resistant Starch: The Missing Link in Non-Alcoholic Fatty Liver Disease (NAFLD) Diet"
New research suggests consuming resistant starch (RS) for 4 months can effectively reduce liver fat content in individuals with non-alcoholic fatty liver disease (NAFLD), independent of weight loss. The study indicates RS alters gut bacteria composition, potentially offering a dietary approach to manage NAFLD. .
DR T S DIDWAL MD
3/15/20246 min read
Recent studies have unveiled a promising avenue in the ongoing battle against non-alcoholic fatty liver disease (NAFLD). Researchers are now reporting that resistant starch, a type of nondigestible fiber, may offer a powerful ally in reducing liver injury, inflammation, and the risk of developing NAFLD. This groundbreaking research, published in the journal Cell Metabolism, has shed light on the potential benefits of incorporating resistant starch into our diets. This study investigated if resistant starch (RS) could help fight fatty liver disease (NAFLD). People with NAFLD took RS for 4 months. Their liver fat content significantly decreased, even if they didn't lose weight. This effect seems linked to changes in gut bacteria caused by RS. One specific gut bacteria, "Bacteroides stercoris," was reduced by RS and is thought to be linked to worse NAFLD. The study suggests RS intake might be a new way to manage NAFLD by influencing gut bacteria and how they function.
Key Findings:
Reduced Liver Fat: Consuming RS for 4 months effectively decreased the amount of fat stored in the liver (intrahepatic triglyceride content, - IHTC), independent of weight loss, in participants with NAFLD.
Gut Microbiome Plays a Role: Changes in gut bacteria composition due to RS intake seem to be responsible for the positive effects on NAFLD.
Specific Bacteria: A gut bacteria species named "Bacteroides stercoris" was found to be closely linked to NAFLD severity and was reduced by RS consumption.
Mechanism: The study suggests that RS alters gut bacteria, leading to lower levels of specific molecules (BCAAs) that contribute to NAFLD development.
Overall, the research indicates that incorporating RS into the diet might be a promising strategy to manage NAFLD by influencing the gut microbiome and its function.
Additional Points:
This study involved a clinical trial with participants, and further investigation using mice supported the findings.
The research highlights the potential for a dietary approach (consuming RS) to address NAFLD, offering a non-invasive intervention.
Introduction
Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as a significant global health concern, affecting approximately 30% of the world's population. This multifaceted condition not only poses a risk for severe hepatic complications but also contributes to the development of various extrahepatic ailments such as type 2 diabetes, cardiovascular diseases, and chronic kidney disease. Despite its prevalence and associated health risks, there remains a dearth of pharmacological treatments approved specifically for NAFLD. In light of this, the exploration of alternative intervention strategies is imperative to mitigate the progression of NAFLD and its associated comorbidities.
Understanding the Gut-Liver Axis in NAFLD Pathogenesis
Accumulating evidence suggests a close interplay between NAFLD and the gut microbiota through the gut-liver axis. This intricate relationship has sparked interest in therapeutic interventions aimed at modulating the gut microbiota to ameliorate NAFLD progression. Among these interventions, microbiota-directed foods (MDFs) have garnered attention for their potential to elicit targeted metabolic responses within the indigenous gut microbiota, thereby conferring health benefits upon the host. Prebiotics and synbiotics, such as oligofructose and yogurt, have shown promise in reducing insulin resistance, intrahepatic lipids, and histologically confirmed steatosis in patients with NAFLD/nonalcoholic steatohepatitis (NASH).
The Role of Resistant Starch in NAFLD Management
Resistant starch (RS), a type of prebiotic, nondigestible fiber fermented in the large intestine, has emerged as a potential therapeutic agent for NAFLD. Previous animal studies have demonstrated its efficacy in reducing adiposity and improving metabolic parameters. However, the therapeutic effects of RS on NAFLD in clinical settings have yet to be explored comprehensively.
Clinical Trial: Investigating the Effects of Resistant Starch on NAFLD
To address this knowledge gap, researchers conducted a randomized, double-blinded, placebo-controlled clinical trial in individuals with NAFLD. The trial, spanning four months, aimed to evaluate the efficacy of RS type 2 from high-amylose maize (HAM-RS2) in alleviating NAFLD symptoms. A total of 200 participants were recruited and randomized to receive either RS (40 g/day) or control starch (CS) with an equal energy supply. Comprehensive clinical measurements, including intrahepatic triglyceride content (IHTC) assessed by magnetic resonance spectroscopy (MRS), were conducted to monitor changes in metabolic phenotypes throughout the intervention period.
Results: Resistant Starch Intervention Alleviates NAFLD
Study findings indicate that RS intervention over four months led to significant improvements in NAFLD parameters among Chinese adults. Participants receiving RS demonstrated reductions in IHTC levels, suggesting a potential therapeutic benefit in mitigating hepatic steatosis. Importantly, adherence to RS intake was high throughout the intervention, underscoring its feasibility as a dietary intervention strategy for NAFLD management.
Implications and Future Directions
The results of this study highlight the promising therapeutic potential of RS in the management of NAFLD. Further research is warranted to elucidate the underlying mechanisms of RS-mediated NAFLD improvement and to validate these findings in larger, more diverse populations. Additionally, long-term prospective studies are needed to assess the sustained efficacy and safety of RS supplementation in NAFLD patients.
The Promise of Microbiome-Directed Therapies
Previous clinical trials have underscored the ability of microbiota-directed foods (MDFs) to modulate immune status and promote healthier metabolic profiles. Among these MDFs, resistant starch (RS) has emerged as a compelling candidate for NAFLD treatment. In a randomized clinical trial, the effects of RS as an MDF for NAFLD treatment were meticulously evaluated, utilizing magnetic resonance imaging (MRI) for precise quantification of changes in liver fat content.
Unveiling the Therapeutic Potential of Resistant Starch
The 4-month intervention with RS demonstrated remarkable efficacy in reducing intrahepatic triglyceride content (IHTC) in NAFLD patients, with an absolute reduction of -5.89% and a relative reduction of -24.30% after adjusting for weight loss. This profound effect was attributed, in part, to the altered composition and metabolic profile of the gut microbiota induced by RS consumption. Notably, fecal microbiota transplantation (FMT) from RS recipients into mice fed a high-fat, high-cholesterol (HFHC) diet resulted in reduced hepatic steatosis and inflammation, affirming the causal role of gut microbiota in mitigating NAFLD.
Molecular Mediators of Resistant Starch Benefits
Amino acids (AAs) emerged as potential molecular mediators of the beneficial effects of RS. Specifically, alterations in AA metabolism, particularly aromatic AAs (AAAs) and branched-chain AAs (BCAAs), were implicated in NAFLD pathogenesis. The RS intervention led to significant reductions in serum levels of phenylalanine, tyrosine, and glutamic acid, as well as BCAAs. Importantly, the correlations between BCAAs and hepatic steatosis remained significant even after adjusting for obesity-related parameters and insulin resistance (IR), highlighting the direct influence of BCAAs on NAFLD pathogenesis.
Exploring Specific Microbial Species
Multi-omics integration analysis identified specific microbial species associated with NAFLD development, notably B. stercoris, which exhibited a positive correlation with IHTC, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The abundance of B. stercoris in the gut was validated in independent case-control cohorts, further substantiating its role in NAFLD progression. Monocolonization studies confirmed the NAFLD-promoting effect of B. stercoris, with implications for LPS and BCAA production.
Implications for FGF21 Sensitization
The intervention with RS also resulted in decreased serum levels of FGF21, a key regulator of lipid metabolism, and enhanced expression of its receptor complex and downstream effectors. This suggests that RS-induced microbiome alterations may sensitize the actions of FGF21, offering a novel avenue for the treatment of metabolic disorders, including NAFLD.
Conclusion
In conclusion, the findings of the study underscore the potential of RS as a microbiota-targeted therapeutic option for NAFLD. The elucidation of RS-induced alterations in gut microbiota composition and functionality provides valuable insights into NAFLD pathogenesis and the development of innovative therapeutics. Further research is warranted to explore additional molecular mechanisms underlying RS benefits and to validate these findings in diverse populations.
Reference Articles
Ni, Y., Qian, L., Siliceo, S. L., Long, X., Nychas, E., Liu, Y., Ismaiah, M. J., Leung, H., Zhang, L., Gao, Q., Wu, Q., Zhang, Y., Jia, X., Liu, S., Yuan, R., Zhou, L., Wang, X., Li, Q., Zhao, Y., . . . Jia, W. (2023, September). Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations. Cell Metabolism, 35(9), 1530-1547.e8. https://doi.org/10.1016/j.cmet.2023.08.002
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