The Microbiome vs Non-Alcoholic Fatty Liver

You’re probably thinking, “How could the gut microbiome possibly interact with the liver?.”

The answer is primarily via the products that your gut microbes produce. Did you know your gut microbes produce substances that interact with your liver cells? Some of these substances include short chain fatty acids, indole, trimethylamine, secondary bile acids, and more. The substances can turn on or off fat metabolism, immune signaling, and your ability to balance antioxidant vs oxidant levels.

The Microbes in NAFLD

The Microbes in NAFLD

A study done on mice transplanted microbial strains B. thetaiotaiomicron and M. smithii into germ free adult mice resulting in fat production by their liver. Furthermore, the mice that were resistant to this had higher levels of the Roseburia and Barnesiella genera, and higher levels of Firmicutes.

Human trials have found higher levels of Enterobacteriaceae, Escherichia and Dorea, decreased Rikenellaceae, Coprococcus and Ruminoccaceae in NAFLD patients. Patients with advanced illness displayed increased gram negative microbes, Proteobacteria, Bacteroides vulgatus, E-coli, Streptococcus and decreased Firmicutes. 

SIBO and NAFLD

Clinical evidence suggests that Non-alcoholic steatohepatitis (NASH) patients have a higher prevalence of small intestinal bacterial overgrowth. SIBO was positive at 34.3% in those with NASH versus 14.8% in those with Celiac Disease and 0% in healthy volunteers.

Studies have also found that administration of antibiotics can improve NAFLD and associated inflammation markers. A good sign SIBO and the microbiome are involved.

Endotoxins and Endproducts

The main microbial endproducts elevated in NAFLD include: LPS, ammonia, ethanol, choline and choline metabolites.

NAFLD patients also have higher serum levels of bile acids, including secondary bile acids., as compared to control patients.

LPS is the strongest endotoxin in the body. Several lines of evidence have shown that increments of circulating LPS impairs intestinal barrier function and causes subsequent increases in intestinal permeability (Leaky Gut). More importantly, LPS that enters into the liver through the portal vein blood activates Kupffer cells and stellate cells via TLR4, which promote hepatic inflammation and fibrosis. In addition, activation of NLRP3 inflammasome induced by LPS has recently been shown to be linked with the progression of NASH.

FMT and NAFL

Faecal microbiota transplant is currently being explored as a treatment for NAFLD in clinical trials. Results of animal studies suggest that FMT improved NASH in mice by improving intrahepatic lipid accumulation, IR, and serum proinflammatory cytokine levels. Another study showed that animals with NAFLD which underwent fecal transplant had decreased hepatic gluconeogenesis and intestinal permeability. In a RCT, patients with metabolic syndrome who received gut microbiota from healthy individuals had increased insulin sensitivity and gut microbial diversity six weeks after FMT.

Prebiotics

Prebiotics and Synbiotics (Probiotic-Prebiotic combinations) are being explored as treatment in clinical trials currently.

Conclusion

Many of the clients I work with do or did have NAFLD as part of their SIBO/IBS dynamic. If SIBO symptoms are present we always start with breath testing. This helps us understand how much focus needs to be placed on microbial reduction and motility and SIBO related root causes vs. being able to start with building up the microbiome. In addition, we work on reducing ammonia, microbially produced alcohol and inflammatory signalling. A root cause analysis can lead us to focus on other areas that need support, that may be promoting SIBO or microbial imbalance.

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