Understanding how microbiota thrive in their human hosts
A research team led by scientists from the Max Planck Institute of Biology, Tübingen, Germany, has now made significant progress in understanding how gut bacteria succeed at the molecular level in their human hosts. They examined how bacteria produce inositol lipids, substances that are essential for many cellular processes in humans and other eukaryotes, but which until now have been rarely observed in bacteria. The results, now published in the journal Nature Microbiologyindicate that inositol lipids have implications for the symbiosis between the bacteria and their hosts.
Microorganisms such as bacteria and fungi inhabit the human gut and contribute to many biological functions such as metabolism or immunity. To understand the influence of the microbiome on humans, researchers have sought to not only identify which microorganisms are present in the human gut, but also shed light on the molecular mechanisms of the interactions between the microbiome and its human host. A research team led by scientists at the Max Planck Institute for Biology in Tübingen has now improved our understanding of these processes by examining how gut bacteria produce a particular family of chemical compounds known as inositol lipids.
Inositol Lipids: Modulators of Inflammation and Cell Signaling
Inositol lipids play an important role in many cellular processes in humans and most other non-bacterial life forms: they regulate how cells send signals throughout the body, modulate inflammation and help ensure that proteins reach the correct part of a larger cell. Imbalances in inositol levels have been linked to diseases such as polycystic ovary syndrome, the most common hormone disorder in women of reproductive age.
Unlike humans and other eukaryotes for whom inositol lipids are essential, bacteria produce them relatively rarely. The research team led by Ruth Ley, scientific director of the Department of Microbiome Science at the MPI for Biology, was able to describe the synthesis of inositol lipids in Bacteroides thetaiotaomicron, a common bacterium in the colon and a popular model organism in microbiome science.
By developing a previously undescribed strain of Bacteroides thetaiotaomicron for which they could check whether inositol lipids were being produced, the researchers found that these substances alter the physiology of the bacteria. “While we don’t fully understand the precise role of inositol lipids for bacterial fitness, we have seen that they are necessary for a bacterium to succeed in the gut of their host,” said Stacey Heaver, lead author of the publication.
The researchers found inositol in the bacteria’s capsule, an outer layer that protects them from being engulfed by the host’s immune cells. In addition, inositol lipids alter the resistance of Bacteroides thetaiotaomicron to antimicrobial peptides, substances used by the host to fight pathogens.
Possible crosstalk between bacterial and host lipids
The researchers also described the metabolic pathways for the synthesis of inositol lipids in Bacteroides thetaiotaomicron, that is, the chain of chemical reactions leading to the production of inositol lipids. They additionally identified a second putative pathway for bacterial synthesis of these lipids. “Finding out the pathways is interesting because it allows us to predict which other microbes can make inositol lipids in the same way as our model organism,” Heaver explains. “With this knowledge, we may even be able to manipulate or manipulate the production of inositol lipids.”
Heaver looks forward to future research on whether and how bacterial inositol lipids may benefit the host organism: “It is possible that there is a crosstalk between the bacterial lipids and the inositol lipids produced by the mammalian host,” she says. “We’ve just come a big step closer to understanding the magnitude of such interactions.”
Stacey L. Heaver et al, Characterization of inositol lipid metabolism in gut-associated Bacteroidetes, Nature Microbiology (2022). DOI: 10.1038/s41564-022-01152-6
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