Review Article

Emerging Role of the Gut Microbiome in the Progression of Nonalcoholic Fatty Liver Disease and Potential Therapeutic Implications

Saumya Jayakumar; Rohit Loomba

Disclosures

Aliment Pharmacol Ther. 2019;50(2):144-158. 

In This Article

Conclusions

The GI tract and the liver develop from the same embryologic origins in the foregut, and this close interrelationship is maintained. Obesity, diet and insulin resistance are common risk factors for the development of NAFLD,[15,83,84] and these risk factors seem to have a strong connection with the gut microbiome.[12] While diet and obesity play a role in the modification of bacteria in the gut microbiota, the bacteria, in turn, affect the ability of host cells to produce and absorb nutrient-derived energy.[34] SCFAs and the ratios of the different fatty acids produced by bacteria are affected by the predominant type of bacteria in the GI lumen. Excess production of certain SCFAs can lead to the accumulation of excess energy in the form of adipose tissue, and obese patients are found to have altered ratios of SCFAs compared with their lean counterparts.[64,66–69] These GI bacteria also affect host lipid metabolism and insulin sensitivity.[77,80,170]

Obesity and insulin resistance are also associated with increased intestinal permeability[171–173] and, therefore, increased rates of bacterial translocation, which activates proinflammatory cascades.[84,170,174,175] Kupffer cell activation by bacterial products such as LPS results in oxidative stress and the development of hepatocyte inflammation and fibrosis. LPS also promote the development of hepatic TG accumulation and hepatic steatosis.[12,100,112,113] There is a strong association between bacterial translocation and the degree of hepatic decompensation in the setting of cirrhosis of any aetiology,[174] and among gut microbiota, BA metabolism, FXR and hepatic steatosis and inflammation.[115,120,121,124] In addition, activation of TLRs by bacterial products results in increased systemic and hepatic inflammation, a major stimulus in the development of NASH and the progression to fibrosis.[100,112,113] Thus, treatment options aimed at targeting the gut microbiome, or the downstream cell-signalling effects of the microbiome, continue to be therapeutic targets for the treatment of patients with NAFLD.

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