Predict Obesity and its complications: better to use our “Other Genome” than our Genome?
Most of the cells in our body are not human but bacterial and are mainly localized in our intestines. The composition of the gut flora of individuals seems to stay stable in adults and thus can be considered as a characteristic of each individual. In that sense, the genome of these bacteria can truly be called our “other genome”. If the heritability of obesity is well proven, the genetic polymorphism explains only a few percent of the Body Mass Index (BMI) and it cannot be used as a reliable predictor of obesity and its complications. ICAN members participated to two articles in the latest Nature’s issue which, together, show that our “other genome” could be used as a better predictor of obesity and of the efficiency of some dietary intervention.
Based on the genes diversity present in the “other genome”, the first study shows the diversity of the gut flora varies a lot between individual and defines a threshold (see graph on the right) between a low diversity (LGC) and a high diversity (HGC). These two groups exist in both lean and obese individuals recruited in the MetaHit European project but most of the LGC individuals were obese. LGC HGC
The LGC individuals also displayed many symptoms, in comparison to HGC, which together bring them at increased risk of pre-diabetes, type-2-diabetes and cardiovascular disorders. Obese LGC individuals also gained more weight in 9 years than obese HGC individuals.
These difference could be assigned to eight bacterial species which were all less abundant in LGC than in HGC individuals and could thus protect against weight gain opening the way in the future for new treatment influencing gut bacteria composition such as probiotic treatment. Furthermore, the study was able to define 18 species which allow to distinguish between lean and obese individuals with a better accuracy than the analysis of 32 human genome loci.
The second study performed in the ICAN clinical investigation platform shows a change in dietary allowed to increase the diversity of the gut flora of obese LGC individuals. A 6-weeks energy-restricted (but fiber rich) diet effectively increased the richness of the LGC individuals’ flora but not for the HGC individuals’ flora. This increase in flora diversity was associated with an overall improvement of their metabolic risks and of their low-grade inflammation*. Although they improve their intestinal bacterial diversity, people with LGC, however, had less improvement in metabolic parameters such as triglyceride levels, and also the low-grade inflammation in adipose tissue and circulating.
Gut flora diversity (Gene richness) for HGCGut flora diversity (Gene richness) for HGC (black line) and LGC (grey line) individuals along 6-weeks energy-restricted and 6- weeks weight-maintenance diets.
Some of the change, but not all, of the composition of LGC individuals’ flora were conserved along a 6-more-weeks of weight-maintenance diet leading to the hope that, even if the gut flora composition is stable in adults, some change in dietary could modify it and so improve the symptoms of obese individuals.
These two studies brings the “other genome “ on the spotlight as good marker and predictor of the metabolic state of individuals and also some new possibilities of preventive and cure treatments.
Cotillard et al. Nature 500, 585–588 (29 August 2013)
Le Chatelier et al. Nature 500, 541–546 (29 August 2013)
Dr. Ludovic Le Chat, Science Attaché ICAN
* Low-grade inflammation: systemic inflammation without a focal origin.