A new mechanism mediating environment-microbe-host interactions

A new mechanism mediating environment-microbe-host interactions

Researchers have uncovered a new mechanism showing how microbes can alter the physiology of the organisms in which they live. In a paper published in Nature Cell Biology, the researchers reveal how microbes living inside the laboratory worm C. elegans respond to environmental changes and generate signals to the worm that alter the way it stores lipids.

"Microbe-host interactions have been known for a long time, but the actual molecular mechanisms that mediate the interactions were largely unknown," said senior author. "Microbes living inside another organism, the host, can respond to changes in the environment, change the molecules they produce and consequently influence the normal workings of the host's body, including disease susceptibility."

C. elegans is a laboratory worm model scientists use to study basic biological mechanisms in health and disease.

"This worm naturally consumes and lives with bacteria in its gut and interacts with them in ways that are similar to those between humans and microbes. In the laboratory, we can study basic biological mechanisms by controlling the type of bacteria living inside this worm as well as other variables and then determining the effect on the worm's physiology," author said.

In this study, authors compared two groups of worms. One group received bacteria that had been grown in a nutritionally rich environment. The other group of worms received the same type of bacteria, but it had grown in nutritionally poor conditions. Both groups of worms received the same amount and type of nutrients, the only difference was the type of environment in which the bacteria had grown before they were administered to the worms.

Interestingly, the worms carrying bacteria that came from a nutritionally poor environment had in their bodies twice the amount of fat present in the worms living with the bacteria coming from the nutritionally rich environment.

The researchers then carried out more experiments and determined that it was the lack of the amino acid methionine in the nutritionally poor environment that had triggered the bacteria to adapt by producing different compounds that then initiated a cascade of events in the worm that led to extra fat accumulation. In addition, the researchers observed that the tissues showing extra fat accumulation also had their mitochondria fragmented. The activities of the mitochondria, the balance between their fusion and breaking apart, are known to be tightly coupled with metabolic activities.

The researchers found that the bacteria were able to trigger mitochondrial fragmentation and then extra lipid accumulation because the molecular intermediates the bacteria had triggered allowed them to 'establish communication' with the mitochondria.

"We have found evidence for the first time that bacteria and mitochondria can 'talk to each other' at the metabolic level," author said.

Bacteria and mitochondria are like distant relatives. Evolutionary evidence strongly suggests that mitochondria descend from bacteria that entered other cell types and became incorporated into their structure. Mitochondria play essential roles in many aspects of the cell's metabolism, but also maintain genes very similar to those of their bacterial ancestors.

"It's interesting that the molecules bacteria generate can chime in the communication between mitochondria and regulate their fusion-fission balance," author said. "Our findings reveal this kind of common language between bacteria and mitochondria, despite them being evolutionary distant from each other."

Some components of this common language involve proteins such as NR5A, Patched and Sonic Hedgehog. The latter is of particular interest to the researchers because it has not been involved in regulating lipid metabolism and mitochondrial dynamics before.

Researchers discovered that methionine deficiency in bacterial medium decreases the production of bacterial metabolites that are essential for phosphatidylcholine synthesis in C. elegans. Reductions of diundecanoyl and dilauroyl phosphatidylcholines attenuate NHR-25, a NR5A nuclear receptor, and release its transcriptional suppression of GRL-21, a Hedgehog-like protein. The induction of GRL-21 consequently inhibits the PTR-24 Patched receptor cell non-autonomously, resulting in mitochondrial fragmentation and lipid accumulation.

"Microbes in the microbiome can affect many aspects of their host's functions, and here we present a new molecular mechanism mediating microbe-host communication," author said. "Having discovered one mechanism encourages us to investigate others that may be related to other physiological aspects, such as the stress response and aging, among others."