Intestinal Bacterial Implicated In Onset of Obesity and Diabetes Interview with:
Prof. Dr. Patrice D. Cani PhD,
Research Associate FRS-FNRS
Louvain Drug Research Instiute, Metabolism and Nutrition
WELBIO, Walloon Excellence in Life sciences and BIOtechnology
NeuroMicrobiota lab, European Associated Laboratory (INSERM/UCL) and
Dr Amandine Everard
Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group, Brussels, Belgium

Medical Research: What is the background for this study? What are the main findings?

Response: Our intestine harbors more than 100 trillions of bacteria. This huge number of bacteria permanently interacts with our own human cells. Among the systems involved in this crosstalk, the immune system plays a key role in these interactions.

We previously showed that specific gut bacteria are able to control energy metabolism, harmful inflammation associated with obesity, body weight gain and type-2 diabetes. However mechanisms involved these effects of gut bacteria on the host during obesity and type-2 diabetes were poorly understood.

We identify the essential role of the intestinal immune system in the onset of obesity and type-2 diabetes both induced by a high dose of fat in the diet. This discovery highlights an unexpected mechanism for the control of energy metabolism during obesity and type-2 diabetes.

We demonstrate for the first time that the inactivation of a part of the intestine immune system (more specifically the protein MyD88), which is overstimulated by a diet rich in fat, allows to induce weight-loss and to reduce type-2 diabetes associated with obesity.

When we tune the immune system by disabling the protein MyD88 specifically in cells covering the intestine, we are able to limit the adipose tissue development induced by the diet rich in fat, to slow down diabetes, to reduce harmful inflammation associated with obesity, to reinforce gut barrier function assumed by our intestine to avoid the inappropriate translocations of bacteria compounds from our intestine in our body.

We reveal various mechanisms explaining the partial protection against obesity induced by the inactivation of this protein of the immune system. Among them, we point out that mice that do not have this protein of the immune system (i.e. MyD88) in their intestine are partially protected against obesity because they spend more energy than other obese mice.

Moreover, our study shows that this protein of the immune system is able to shape the composition of the gut microbiota residing in our intestine under a high-fat diet. These changes observed in mice deleted for this protein also explain their protection against obesity because when we transfer intestinal bacteria of these mice into other mice that are axenic (without flora), these latest mice are also partially protected against obesity.

In conclusions, our studies published in the scientific journal Nature Communications, demonstrated that during consumption of fat food, the intestinal immune system plays an important role in fat storage regulation in the body and is capable to modify the composition of intestinal bacteria (including some which are still unidentified), confirm the implication of intestinal bacteria in the onset of obesity.

Medical Research: What should clinicians and patients take away from your report?

Response: When we approach obesity and metabolic disorders, we have to take into account the disease in its entirely and the totality of the organs and systems involved in this disease. If obesity is defined as an excessive fat mass accumulation, this disease is more complex than simply fat mass accumulation and a lot of organs and system are involved even if there are located at distance from the adipose tissue. The intestine and the gut microbiota act as master factors in the onset of obesity and type2 diabetes. This observation is not completely far fetched since intestinal cells are the first cells being in contact the nutrient. Moreover our study clearly unravel the essential role of intestinal immune system in obesity and type-2 diabetes revealing that this immune system has also to be considered in these disorders.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: We think that these results mainly provide new opportunity for the development of a putative therapeutic tool, mainly by targeting a protein of the intestinal immune system (MyD88) for the treatment of obesity and type-2 diabetes. This is the first study showing that the intestinal immune system plays a key role in body weight regulation. This is a very interesting advance since nowadays no drug without side effect is available to tackle efficiently obesity and related metabolic disorders. However since this discovery is based on genetic modification (mutation) in research animal, a lot of work and future researches should still be performed in order to develop a specific medicine able to invalidate this protein in the intestine of obese human patients.


Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status Amandine Everard et al
Nature Communications 5, Article number: 5648 doi:10.1038/ncomms6648 Published