Editors' ChoiceMicrobiome

Blame the gut for a fatty liver!

See allHide authors and affiliations

Science Translational Medicine  25 Jul 2018:
Vol. 10, Issue 451, eaau8085
DOI: 10.1126/scitranslmed.aau8085


Microbiota dysbiosis may play a key role in triggering hepatic steatosis in nondiabetic obese women.

Hepatic steatosis refers to the excessive buildup of lipids in the liver with the propensity to develop liver inflammation, leading to progression into end-stage liver disease. The condition is commonly associated with insulin resistance in obesity, but the mechanisms remain speculative. Here, Hoyles et al. utilized omics phenotyping technologies to describe the link between the microbiota and hepatic steatosis in nondiabetic obese women.

In their study, the authors included two cohorts of morbidly obese women without evidence of type 2 diabetes, and a range of biological samples were collected from them for investigation. To characterize the link between the microbiota and hepatic steatosis development, the investigators analyzed the microbiota metagenomes from patient fecal matter and found that women with severe hepatic steatosis had reduced diversity of microbiota genes. Molecular phenotyping of liver, serum, and urine samples from the same set of patients showed that genes associated with both liver inflammation and the insulin receptor were linked to microbiota diversity. To validate these findings, the investigators examined the role of the gut-brain axis by transplanting fecal microbiota from patients with severe hepatic steatosis into recipient mice. They reported that transplanted mice developed hepatic steatosis and shared similar molecular characteristics of steatosis as in the donors.

Another physiological disruption identified in women with severe hepatic steatosis was microbiota-driven amino acid metabolism. The investigators examined the contributions of the microbial metabolite phenylacetic acid (PAA), a product of phenylalanine metabolism, in hepatic steatosis. They observed that chronic treatment of PAA was sufficient to induce features of hepatic steatosis in human hepatocytes and mice.

From these findings, microbiota dysbiosis and particularly PAA provide a possible explanation for hepatic steatosis development. Future studies should investigate whether probiotics and antibiotics (which alter the gut microbiome) could influence disease development. This could help identify dietary interventions that could reverse the progression of hepatic steatosis in obesity.

Highlighted Article

Stay Connected to Science Translational Medicine

Navigate This Article