Obesity and NASH: The Bugs don’t Work. Or do They?

Insights on the Gut Microbiome, Obesity, and NAFLD: Part I

 

The human gastrointestinal (GI) tract is home to trillions of microorganisms, often collectively termed the gut microbiota (or microbiome when considering the associated genome). This vast array of life contains many times more cells (and genes) than in the whole human body. As such, there has been more and more interest in the influence these myriad organisms may have on human health. In particular, the effects of the gut microbiome’s impact on obesity and fatty liver disease have been subject to a growing body of research, hardly surprising considering the links between food intake, the gut, and increased adiposity. Now as we approach the holiday season, and the edible delights that come with it, two of our experts at DRG give their thoughts on the role the microbiome has in obesity and fatty liver disease and the potential for developing drugs from the bugs.

 

You are what you eat…

We are fat. And getting fatter. We all have trillions of microorganisms in our guts metabolizing food (and medicines), synthesizing vitamins, and preventing pathogen colonization, as well as modulating immune and endocrinological functions and responses. Research has already shown that the gut microbiota of lean people and obese can be significantly different. To me, it stands to reason that with this interdependence we must be able to optimize our microbiome or engage it to help treat the obesity epidemic that is driving the growing incidence of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes, among other problems.

 

Studies of certain probiotics have demonstrated positive effects of fatty acid production, weight gain, and energy metabolism.1 In murine studies, germ free animals appeared to have some degree of protection against obesity; transplanting gut microbes into germ-free mice led to increases in body fat.2

Fecal microbiota transplant from lean people to those with insulins resistance demonstrated an improvement in insulin sensitivity.3 In addition several prebiotics studies have shown anti-adiposity effects.4

 

… and you are what is eating what you eat…

The connection between the gut and liver from the portal venous system directly exposes the liver to the metabolites and byproducts of the gut microbiota. Like obesity, more and more evidence has been developed suggesting a prominent role of the gut microbiota in the development of nonalcoholic fatty liver disease via inflammation, metabolites, lipopolysaccharides, bile acids, and fatty acids.5 Moreover, there is evidence that certain changes in the gut flora can affect the ability of the GI tract as a barrier, the “leaky gut model”, leading to translocation of pathogens and eventually liver inflammation.5 Probiotics have also been associated with benefit for NAFLD patients, including improved liver transaminases, lipid profiles, and insulin resistance.6 Other probiotics trial have demonstrated benefits in liver function tests independent of BMI, as well as reductions in steatotis.7

 

…so targeting bugs could be as good as developing drugs.

We are increasingly recognizing the interdependence we have with our gut microbiota. This relationship and the research completed so far suggests that the gut microbiota and microbiome could offer a wealth of targets for treating obesity and NAFLD. Its early days but drugs from the bugs (or their genes) are not far away.

 

For further insights on the gut microbiome, obesity, and NAFLD from DRG’s Gideon Heap, please click here.

 

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References

  1. Brusaferro A, et al. Is It Time to Use Probiotics to Prevent or Treat Obesity? Nutrients. 2018 Nov 1;10(11). pii: E1613.
  2. Davis CD. The Gut Microbiome and Its Role in Obesity. Nutr Today. 2016 Jul-Aug;51(4):167-174.
  3. Vrieze A, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–916.
  4. Kho ZY and Lal SK. The Human Gut Microbiome - A Potential Controller of Wellness and Disease. Front Microbiol. 2018 Aug 14;9:1835.
  5. Bashiardes S, et al. Non-alcoholic fatty liver and the gut microbiota. Mol Metab. 2016 Jun 14;5(9):782-94.
  6. Ma YY, et al. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013 Oct 28;19(40):6911-8.
  7. Roychowdhury S, et al. The Role of the Gut Microbiome in Nonalcoholic Fatty Liver Dis Med Sci (Basel). 2018 Jun 5;6(2). pii: E47.