The intestinal microbiome is attributed as having a great impact on our health. However, the mechanisms behind this are still largely unknown. Scientists from the Max Planck Institute for Developmental Biology in Tübingen, Germany, have now provided evidence that intestinal bacteria have a direct influence on the lipid metabolism of their host. They published their results in the journal Nature Communications.
The human body contains around ten times as many microorganisms as actual human cells. Particularly prominent are the microbial “communities” 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 microorganisms living in our bodies 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. And if it weren't enough: the microorganisms in the intestine play a role in determining the health and illness of their host.
The detailed mechanisms by which intestinal microbes influence the metabolism of their host 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 looked into such mechanisms by using sphingolipids as an example. An imbalance in the sphingolipid population is associated with metabolic disorders such as insulin resistance or fatty liver.
The human body can synthesize sphingolipids by itself. "However, the intestinal microbiome contains a remarkably high proportion of bacteria that also produce sphingolipids," said Ley, adding that "this affects around 30 to 40 percent of the microbiome, i.e. it is so dominant that it seems likely that the bacterial sphingolipids play a role in the host". However, so far, it is only known that the bacterial sphingolipids are involved in the signaling pathways of the inflammatory immune response in the intestine. It has not yet been clarified whether they are also involved in a host’s lipid metabolism.
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 investigate the role of sphingolipids from the microbiome in the living organism, the Max Planck research team worked with mice that had been sterilely bred and were not colonized by any microorganisms. These animals have significantly altered lipid metabolism compared to mice with a normal microbiome. Thus, the aseptically kept animals produce more sphingolipids in the liver than their conspecifics that grow up under normal conditions.
This changed dramatically when the researchers led by Ruth Ley inoculated the germ-free animals with the sphingolipid-synthesizing microorganism Bacteroides thetaiotaomicron. From then on, the sphingolipid production in the liver of the animals was reduced to a normal level.
In addition, bacterial sphingolipids could also be detected in the blood of rodents - but not in the liver itself. It is assumed that the lipids are involved in the metabolism without being transported to the liver. The researchers believe that it may be possible they are converted before they reach the liver, or that they send signals to the liver. "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 metabolism," said Ley.
Scientists still need to find out whether this finding can also be confirmed in the human organism. Nevertheless, the results of the Max Planck team already provide decisive indications as to how the microbiome can directly influence the lipid metabolism, and by extension, our health.
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