Intestinal bacteria influence the metabolism as suppliers of important fats

Scientists attribute an important significance for health to the microbiome in the intestine. However, it is still largely unknown what mechanisms are behind this. Scientists from the Max Planck Institute for Developmental Biology in Tübingen have now provided evidence that intestinal bacteria have a direct influence on the fat metabolism of their host. They published their results in Nature Communications.

Bacteroides thetaiotaomicron, the sphingolipid-producing bacteria used in the study. Copyright: Jürgen Berger / MPI for Developmental Biology

The human organism contains around ten times as many microorganisms as human cells. Particularly prominent are the microbial ´flatshares´ on the skin and in the intestine. They perform a protective function and prevent, for example, the spread of pathogens. But in the last 15 years it has become increasingly clear that these ´flatmates´ living in the body can do much more. They support the immune system, digestion and the absorption of nutrients into the blood. They provide valuable vitamins and building blocks and even influence the mind. Finally: The microorganisms in the intestine play a role in determining the health and illness of their host.

The mechanisms by which intestinal microbes influence the metabolism of their host in detail are still largely unknown. It is also not always clear what role the nutrients and building blocks produced by the microbes actually play for the host organism. Ruth Ley, Director at the Max Planck Institute for Developmental Biology in Tübingen, and her team have now investigated this, using sphingolipids as an example. Sphingolipids are an important group of lipids, i.e. fat molecules that are fundamental components of the cell membrane and also of many signalling molecules. An imbalance in the sphingolipid balance is associated with metabolic disorders such as insulin resistance or fatty liver.

The human body can synthesize sphingolipids itself. In addition, the fats are absorbed through food. "However, the intestinal microbiome contains a remarkably high proportion of bacteria that also produce sphingolipids," said Ley. "This affects around 30 to 40 per cent of the microbiome, i.e. it is so dominant that it seems likely that the spingolipids from bacteria play a role in the host," said Ley. However, so far, it is only known that the bacterial sphingolipids are involved in the signalling pathways of the inflammatory immune response in the intestine. It has not yet been clarified whether they are also involved in the fat metabolism of the host.

Ruth Ley and her team initially used cell culture experiments to show that human cells are able to use the sphingolipids from the bacteria for their metabolic activities. At the same time, the presence of bacterial sphingolipids reduces the cells' own production.

In order to test the role of the sphingolipids from the microbiome in the living organism, the Max Planck scientists from Tübingen worked with sterile mice that were not colonized by any microorganisms. These animals have a significantly altered fat metabolism compared to mice with a normal microbiome. For example, the aseptically kept animals produce more sphingolipids in the liver than their conspecifics that grow up under normal conditions.

This changed dramatically when Ruth Ley's team of scientists inoculated the germ-free animals with the sphingolipid-synthesizing microorganism Bacteroides thetaiotaomicron. From then on, the sphingolipid production in the animals' liver was reduced to normal levels.

In addition, bacterial sphingolipids could also be detected in the blood of the rodents - but not in the liver itself. It is assumed that the fats are involved in the metabolism without being transported to the liver. It is possible that they are converted before they reach the liver, or that they send signals to the liver, the scientists believe.  "The fact that the sphingolipid synthesis in the animals' liver is reduced by the presence of bacterial sphingolipids clearly shows us that they have an effect on the metabolism," said Ley. We still need to find out whether this finding can also be confirmed in the human organism. Nevertheless, the results of the Max Planck researchers already provide decisive indications as to how the microbiome can directly influence the fat metabolism and thus health.

 

Scientific contact:

Prof. Ruth Ley, Ph.D.
Max Planck Institute for Developmental Biology
Phone: 07071 601-449
e-mail: ruth.ley(at)tuebingen.mpg.de

 

Original publication:

Johnson EL, Heaver SL, Waters JL, et al Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Nat Commun. 2020;11(1):2471. published 2020 May 18. doi:10.1038/s41467-020-16274-w