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Rich or poor in gut bacteria: we are not all equal facing obesity associated diseases
Published simultaneously today in Nature, two studies could lead to important outcomes in the field of preventive and personalized medicine. Carried out by INRA in France jointly with French and international partners*, these studies showed for the first time that 2 groups of individuals can be distinguished in the population, according to differences in the richness of their gut bacteria (microbiota). Scientists observed that individuals lacking gut bacteria (diversity depletion) are at greater risk to develop diseases associated with obesity. Parallel to this, they succeeded in improving the microbiota composition thanks to a specific diet. It would therefore be possible to develop a simple identification test for these people at risk and offer them a dedicated preventive solution.
The obesity epidemic affected 400 million adults in 2005; it will affect more than 700 million in 2015 and will continue to grow. The causes are partly due to external factors (sedentary lifestyle, high energy food easily obtained…) and partly due to genetic factors. However, the latter seem to count for only a minor part of the trend. More and more data show that variations in our “other” genome, the microbiome, i.e. the global genome of all microorganisms we host in our bodies, may have greater consequences on the onset of obesity than variations in the human genome.
Two groups of individuals according to the bacterial composition of the digestive tract
A first study conducted by the MetaHIT* consortium focused on a cohort of 292 Danish adults, comprising 123 non-obese and 169 obese. The scientists analyzed their gut bacterial genome with the help of a new analytical approach called quantitative metagenomics. They found that two groups of people can be distinguished by the richness of bacteria they carry and the abundance of certain bacterial species. A quarter of the cohort is “poor” in bacteria, whereas the rest is “rich”. “This is the first time we find evidence of such a distinction in the population. Besides, this distinction is not dependent on corpulence since lean and obese are found in both groups, even though 80% of the low bacterial richness group are obese”, explains Stanislas Dusko Ehrlich, corresponding author of the study.
An increased risk of obesity-associated complications
When comparing the two groups, scientists discovered that people with a poor microbiota have more body fat, are more resistant to the action of insulin, have unfavorably altered blood lipids and show increased blood levels of inflammation markers and white blood cells, bringing them at increased risk of contracting pre-diabetes, overt type 2 diabetes, cardiovascular disorders and possibly cancer.
Some bacterial species limit weight gain
Researchers also observed that obese people from the poor group gain more weight over time than the lean ones. These individuals either lacked entirely or had a very low abundance of eight particular bacterial species, which might therefore have a protective role against weight gain. Their discovery could, in turn, lead to the development of new probiotics which help fight against weight gain.
Six bacterial species suffice to differentiate the “poor” from the “rich”
The second study conducted by the French consortium MicroObes* on a cohort of 49 French obese or overweight persons, confirms the results of the first study. The low or high bacterial communities are similar in both French and Danes. Moreover, it is possible to differentiate the “rich” communities from the “poor” ones with only six typical bacterial species, with an accuracy of 95%. These results could lead to the elaboration of a simple method to determine what type of microbial community an individual carries.
A specific diet enriches the microbiota
The French study focused on the impact of a diet, high in protein and fiber, and low in calories, on the richness of the gut microbiota. This diet, after 6 weeks, led to not only an expected improvement of the clinical characteristics of the individuals under study, but also to an increase of the richness within the poor group. Scientists were thus able to correlate the increase of the bacterial richness with the weight and fat loss. The way is now open not only for diagnosis of individuals at risk but also to nutritional recommendations to help them.
However, chronic inflammation could not be corrected by diet within the poor group as efficiently as in the rich group, indicating the need for personalized treatments. Other means may be required for this, possibly medication.
“A hope for future is that clinical signs associated with obesity could be corrected or even better prevented by the early detection of microbiota alteration and specific nutritional recommendations” says Dusko Ehrlich. The two studies thus pave the way to a preventive medicine for chronic diseases, an alternative to curative treatment the cost of which for industrialized societies becomes more and more financially unsustainable.
Emmanuelle Le Chatelier et al. Richness of human gut microbiome correlates with metabolic markers. Nature, 29 August 2013. DOI: 10.1038/nature12506
Aurélie Cotillard et al. Dietary intervention impact on gut microbial gene richness. Nature, 29 August 2013. DOI: 10.1038/nature12480
* Two research consortia focusing on the human gut microbiota
MetaHIT (METAgenomics of the Human Intestinal Tract) is a FP7 research project, coordinated by INRA, that ended in June 2012 and gathered within an international consortium 14 European research institutions and private firms (France, Germany, Denmark, Spain, Italy, Netherland, UK) and China. http://www.metahit.eu/
MicroObes (Human gut microbiome with obesity and nutritional transition) is a program funded by ANR, coordinated by INRA, that ended in January 2011 and gathered 5 research units from INRA, INSERM, AP-HP, CEA. http://www7.inra.fr/micro_obes_eng/le_projet