Longevity Briefs: A Single Gut Microbe That Prevents Weight Gain In Mice

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

As we age, the diversity of microorganisms living in our gut (collectively known as the gut microbiota) tends to decline. This is now believed by many to be an important component of ageing and a contributor to some age-related diseases. A healthy gut microbiota helps prevent infection by out-competing foreign pathogens. Some gut bacteria are also able to synthesise molecules that have beneficial effects on human cells in the intestinal wall, and may even benefit distant organs via the bloodstream. Unsurprisingly, the gut microbiota also has a significant impact on how we respond to diet, while our diets can shape our microbiota for better or for worse.

In the hope of harnessing the benefits of the microbiota, some efforts have been made to identify which specific bacteria and bacterial products are ‘good’ and which are ‘bad’ for health. This is no easy task, as there are thousands of strains of bacteria living within the human gut, and the exact composition of the microbiota varies from one person to another. There are trends linking certain types of bacteria to health, but a single bacterium with significant health impacts is a rare find. In this study, researchers identify one such bacterium, at least in mice.

The discovery:

The research team isolated a single gut bacterium, Turicibacter (strain KKT8), that appears to protect mice against weight gain.

Human databases showing a correlation between low Turicibacter population and being overweight first prompted researchers to study Turicibacter in mice. Researchers then took germ-free mice (mice without any microbes) and gave them either a subset of gut spore-forming bacteria containing Turicibacter, or Turicibacter alone. They found that both groups gained less weight and had lower intestinal fat uptake than germ-free controls when fed a normal chow diet. However, when these mice were fed a high‑fat diet (HFD), Turicibacter abundance dropped and its protective effect was lost, suggesting that fat intake remodelled their microbiota composition.

To investigate how Turicibacter might be influencing fat uptake, the researchers used genetic sequencing and mass-spectrometry to study gene expression in gut epithelial cells as well as measuring lipid levels in cells and in blood. They found that Turicibacter altered the expression of genes controlling lipid uptake in epithelial cells while reducing ceramide levels in the blood and intestine. Ceramides are a type of lipid that, when elevated, appear to contribute to fat accumulation and type II diabetes.

Looking at Turicibacter in culture, researchers found that it produced unique bacterial lipids that suppressed fat uptake and ceramide production in epithelial cells. Administering either Turicibacter or its lipid products to mice that were fed a high-fat diet reduced weight gain in these mice, suggesting that these lipids were responsible for the protective effects of Turicibacter in previous experiments.

The implications:

Though yet to be confirmed in humans, this study suggests that Turicibacter can single-handedly reduce weight gain in mice fed a high-fat diet, and provides a mechanistic explanation: the lipids produced by Turicibacter suppress fat uptake by intestinal cells and suppress ceramide production. Ceramides are strong predictors of both metabolic conditions (like diabetes) and cardiovascular disease. Loss of Turicibacter with advancing age might contribute to increasing risk of these conditions, while high fat diets could accelerate the process.

Gut microbes play an important role in the digestive process. Diet shapes the microbiota composition, which in turn shapes how we respond to diet and may even influence the types of food we crave. Speculatively, this is probably a good thing from an evolutionary perspective – if our environment changes and forces a change of diet, say an increase in fat intake, then the microbiota composition may shift in a way that improves our ability to absorb fat. However, this becomes a problem when the change in diet is sustained long-term, leading to a microbiota composition that drives weight gain and age-related disease. Fortunately, these changes should be relatively easy to reverse if we can figure out which microbes are responsible. Given the finding that a single bacteria can prevent weight gain, this might be a more realistic goal than we initially thought.