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Gut microbes can cause obesity, and we're getting closer to understanding how

ScienceAlert Feb 08, 2022

Medical researchers have discovered a molecule linking the tiny creatures that call our guts home to levels of fat in our bodies.

"We now have a molecular mechanism that provides a starting point to understand our microbiome as a link between our diet and our body composition," explained Emory University biochemist Dean Jones.

Hints of this link have been growing for some time now as we've been learning just how much this ecosystem of microbes within us – populated by bacteria, yeast, and other microbes and their parasites – can powerfully influence our health, lifespans and shape our bodies.

Recent studies have even suggested that leanness or weight gain could be contagious, through the spread of different microbes. 

The rise of the obesity epidemic in modern times has coincided with massive changes in our gut microbiomes. But obesity, with its associated health problems, including heart disease and diabetes, is a complicated condition involving the interplay between our genes, environment, and diet as well as our microbiome composition.

Studies have revealed 10% of circulating metabolic molecules in mice can be traced back to their microbiome, so molecular biologist Ken Liu and colleagues decided to examine these chemicals more closely.

They detected the molecule delta-valerobetaine in mice exposed to microbes, but not in microbiome-free mice raised and kept in pristine conditions as a control group. Using cell cultures, the team demonstrated that delta-valerobetaine decreased the levels of carnitine.

One of carnitine's roles in our bodies is to transport long fat molecules into the mitochondria – our cells' powerplant – where it is broken down to be used for energy. So when mice with delta-valerobetaine were fed fattier Western diets, they were unable to make efficient use of it without enough carnitine. The mice gained weight and accumulated more fat in their livers; the mice on the normal, control diet maintained their weight levels.

While the researchers couldn't directly show this mechanism in humans, correlations between levels of delta-valerobetaine, carnitine, and body fat levels all matched up. In 214 humans, they found the average blood levels of delta-valerobetaine was 40% higher for people with a BMI greater than 30 compared to those with lower BMIs.

Emory University pathologist Andrew Neish explained that some types of bacteria likely produce more delta-valerobetaine than others. This would explain how factors influencing our microbiome composition, from diet to who we live with and what medications we take, also change how our microbiome affects our weight.

In an accompanying review of the study, Vanderbilt University nutrigenomicist Jane Ferguson points out that delta-valerobetaine is also present in common foods, including meat and milk, and has been found to play a role in reducing cancer cell viability.

"Thus, delta-valerobetaine may have both positive and negative effects on host health," she wrote.

Liu suspects that mammalian bodies' sensitivity to delta-valerobetaine may have evolved as a way to promote fat storage for when food was scarce.

"This type of information could potentially help someone develop a personalized strategy for weight loss," Liu said. "But there are a lot of things we need to understand better about how delta-valerobetaine functions in context."

Their research was published in Nature Metabolism.

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