Editors' ChoiceMetabolism

Dieting bacteria cure fatty liver disease

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Science Translational Medicine  14 Mar 2018:
Vol. 10, Issue 432, eaat1638
DOI: 10.1126/scitranslmed.aat1638

Abstract

Lowering carbohydrate intake treats fatty liver disease in humans by changing gut microbial composition and metabolism.

Nonalcoholic fatty liver disease (NAFLD) is an early stage liver disease that can progress into liver failure and hepatocellular carcinoma; it is also a risk factor for cardiometabolic diseases, including type 2 diabetes. NAFLD is characterized by massive lipid infiltration and de novo lipid synthesis in the liver. So far, the best way to stop disease progression is a low-carbohydrate diet, but the mechanisms underlying the successful intervention are poorly understood, especially due to most studies being confounded by concomitant weight loss.

Mardinoglu and colleagues prescribed a low-carbohydrate dietary intervention in patients with NAFLD over two weeks. To eliminate bias from weight loss, they provided an isocaloric diet in which carbohydrates were replaced by protein. As expected, fat content in the liver declined after the full two weeks, and remarkably, change was even detectable after just one day of dieting. These changes coincided with a metabolic shift from lipogenesis to lipid oxidation and were accompanied by a reduction in markers of liver damage and inflammation.

The authors ascribe the physiological benefits of the low-carbohydrate diet to changes in the gut microbiome. Indeed, one day of diet was sufficient to alter the gut microbial composition, and this transition continued throughout the first week of treatment. Folate-producing bacteria became more abundant, plasma folate levels increased, and folate cycle genes increased in expression when measured in liver biopsies of the dieting patients. Given that folate deficiency was previously linked to hepatic inflammation and fat metabolism, these key observations may explain the improved lipid homeostasis in NAFLD patients undergoing the low-carbohydrate intervention.

Altogether, this elegant study marks an important new step toward an integrated understanding of how diet, microbiota, and host genetics interact and contribute to the pathophysiology of NAFLD. Following up on these findings, it will be worth testing whether fecal microbial transplantation with folate-producing bacteria, or, more simply, micronutrient supplementation (e.g., with folate) can achieve similar effects without the need to change the diet.

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