New research explains why the same high-fat diet affects people differently. The team found that they could predict which mice would gain more weight and develop glucose intolerance after switching to a high-fat diet by using gut microbe signatures that were present before the switch.
In a paper published in Cell Reports, researchers from Imperial College London in the United Kingdom and INSERM UMRS 1138 in Paris, France, among others, describe how they used genetically similar mice to show that gut microbes influence the body’s response to changes in diet and affect health.
If further research finds that the effect is also true of humans, the researchers believe that it could lead to doctors prescribing personalized diets for patients based on the unique composition of their gut flora.
“We know that our environment and genetics can influence our risk of obesity and disease, but the effects of these communities of bacteria living inside us are less well understood,” says study leader Dr. Marc-Emmanuel Dumas, a reader in translational systems medicine at Imperial College London.
The human gut, which represents one of the largest interfaces between the body and the environment, is home to vast colonies of bacteria and other microbes that have co-evolved with their hosts over thousands of years to play a vital role in health and disease.
From the day we are born, our gut microbiome – that is, the collection of gut microbes and their genetic material – is not only helping to digest food and make vitamins, but it is also shaping our immune system and the way our body responds to agents of disease.
Scientists are also starting to uncover a vast and complex system through which gut microbes might influence human brain development and behavior through their metabolites, the chemical byproducts of their activity.
It has also been established that diet is one of the main factors in shaping the gut microbiome over the course of life.
Now, Dr. Dumas and colleagues also show that there could be an effect in the other direction: that the gut microbiome may determine how the body responds to diet.
For their study, the researchers placed around 50 mice with similar genetic makeup on a high-fat diet and tracked changes in their health and behavior.
Before switching the mice to the high-fat diet, the team used magnetic resonance spectroscopy to screen urine samples from the animals for metabolites of their gut microbes. This yielded a “gut microbiome signature” for each animal.
The high-fat diet resulted in several changes in the mice, but not all of them were affected in the same way, despite the fact that they were genetically similar.
Some mice put on more weight than others, and some became less tolerant of glucose. Glucose intolerance is an early sign of diabetes. There were also some changes in behavior, such as in levels of anxiety and activity.
Analysis against the animals’ gut microbiome signatures showed that they were predictive of some of the changes. The team found that one metabolite in particular, called trimethylamine-N-oxide, was an accurate predictor of glucose intolerance.
Co-senior author Jeremy K. Nicholson, a professor and head of the Department of Surgery and Cancer at Imperial College London, explains that in early life, “we start off with very few bugs” and our microbiome enlarges as we acquire more microbes from our environment.
“This means that small differences in the local environment can result in a great diversity in terms of the microbiome,” he adds, as he sums up the research:
“This study is another fascinating example of the power of the microbiome to influence the host with respect to major health risks. It shows that value of a diet is determined not only by your genes, but also the genes of your gut microbes.”