Gut microbiota may modulate liver metabolism

Researchers have found that the gut microbiota could contribute to liver function through the transfer of bacterial sphingolipids to the host’s liver.

What is already know
Metabolites produced by the gut microbiota can contribute to host health and disease. For example, bioactive sphingolipids (SLs), a class of lipids involved in energy metabolism, are produced by Bacteroides and Prevotella bacteria. SLs have been implicated in immune system modulation and decreased intestinal inflammation. But although it is known that bacterial sphingolipids can alter SL levels in the liver, the effects of bacterial sphingolipids on liver health remain elusive.

What this research adds
Researchers characterized and traced bacterial sphingolipids produced by the gut microbe Bacteroides thetaiotaomicron in mice. The researchers identified a previously unknown bacterial sphingolipid that transits to the colons and livers of mice. In a mouse model of hepatic steatosis — a condition characterized by increased build-up of fat in the liver, sphingolipid production rescued the excessive storage of lipids. Adding this sphingolipid to liver cells reduced the production of fat, the team found.

Conclusions
The findings suggest that the gut microbiota could contribute to liver function through the transfer of bacterial sphingolipids to the host’s liver.

Metabolites produced by the gut microbiota can contribute to host health and disease, but their effects in specific tissues remain elusive. Now, researchers have found that a specific class of lipids can modulate liver metabolism in mice.

The findings, published in Cell Host & Microbe, suggest that the gut microbiota could contribute to liver function through the transfer of bacterial lipids to the host’s liver.

Bioactive sphingolipids (SLs) are produced by Bacteroides and Prevotella bacteria and have been implicated in immune system modulation and decreased intestinal inflammation. But although it is known that bacterial sphingolipids can alter SL levels in the liver, the effects of bacterial sphingolipids on liver health are unclear.

To address this question, Elizabeth Johnson at Cornell University and her colleagues developed a method to characterize and trace bacterial sphingolipids produced by the gut microbe Bacteroides thetaiotaomicron in mice.

Bacteria-derived lipids

The researchers identified a previously unknown bacterial sphingolipid that transits to the colons and livers of mice. The transfer was not observed using a strain of B. thetaiotaomicron that is unable to produce sphingolipids, the researchers found.

“Despite extensive efforts to characterize other B. thetaiotaomicron-derived lipids that transit to the liver, thus far, our methods have detected only this specific candidate SL,” the researchers say. However, they note, other derivatives of bacterial SLs likely transit to host tissues.

Further analyses showed that the metabolism of fatty acids — the building blocks of fat in the body — was altered in mice with a sphingolipid-producing microbiota. Adding the B. thetaiotaomicron-derived sphingolipid to liver cells reduced the production of fat by improving respiration in cells incubated with excess sugar.

Fat build-up

Next, the team set out to monitor lipid-dependent metabolic effects in the liver. To do so, they fed mice a fat-free diet for two weeks. This diet results in excess storage of fat in the liver and the onset of hepatic steatosis — a condition characterized by increased build-up of fat in the liver.

Sphingolipid production rescued the excessive storage of lipids in mice with hepatic steatosis. Rodents with a sphingolipid-producing microbiota also showed higher expression of genes involved in lipid metabolism.

“Our metabolomic and gene expression data from hepatocytes and mouse livers suggest that the transfer of lipids from sphingolipid-producing bacteria may, directly and indirectly, decrease hepatic lipid accumulation induced by a fat-free diet,” the researchers say.

The findings may help to develop dietary approaches or drugs to target bacterial sphingolipid metabolism for therapeutic use, they add.