Humanity faces an unprecedented epidemic of obesity, diabetes and cardiovascular diseases. Intestinal bacteria and their dialogue with the immune system have something to do with it.
We have 100 quadrillion bacteria in our digestive system. This intestinal microbiota (also called intestinal flora) is indispensable to our body’s health. It helps us digest, but that’s not all. ‘We suspect the intestinal microbiota plays a fundamental role in the appearance and development of obesity and related metabolic disorders: type 2 diabetes (or adult diabetes), cardiovascular disorders, etc.’, explains Prof. Patrice D. Cani, co-director of the UCL Metabolism and Nutrition Research Group.
We’re not all equal when faced with these diseases. Take two people of the same age and sex, who exercise and eat similarly: one will maintain stable weight while the other gains wait and/or develops type 2 diabetes. ‘The difference, which has also been observed among identical twins, could be due to the composition of their microbiota and the constant dialogue between it and other systems of the human body.’
To each his own microbiota
Intestinal microbiota is composed of numerous bacterial families. Just about all of them are in each of us, though their proportions vary. Based on a series of factors (genetics, age, sex, nutrition, medical preconditions, etc.), each microbiota has its own composition specific to the individual. For example, we know that obese and diabetic persons have a less diverse microbiota than others do.
Between 1,000 and 1,500 bacterial species exist. ‘In my laboratory, we’re very interested in Akkermansia muciniphila’, Prof. Cani says. ‘We discovered that this bacterium, which is present in great quantity in the microbiota, seems to protect against metabolic disorders. Even better, when following the same low-calorie diet, an individual with a high level of Akkermansia loses more visceral fat and reduces cardiovascular risk factors further than an individual with a lower level.’
Another research front: links between the microbiota and the immune system. Almost three-quarters of our immune cells are in our intestinal walls. Thus they’re in direct contact with intestinal bacteria and the compounds produced by their metabolism (metabolites). Yet some of the bacteria are pathogens, that is, they’re likely to make us sick. All’s well as long as these ‘bad’ bacteria are few and cause no trouble. But if they proliferate, they can cause gastroenteritis, inflammation, diarrhoea, etc. ‘Immune cells are the sentinels of our intestine. They trap substances and receive information released by bacteria and, if necessary, attack them. For their part, bacteria also influence our immune system, which is both innate (present at birth) and acquired: it evolves and diversifies in accordance with the microorganisms (bacteria, viruses, etc.) we encounter throughout our lives. In short, microbiota and immune system work hand-in-hand and influence each other.’
What’s this have to do with obesity? ‘We think that by slightly changing the innate immune system (by improving communication between certain bacteria and our body, for example), we might be able to protect the person against obesity and related metabolic disorders. That’s what our laboratory experiments are telling us.’
Microbiota and fat storage
Prof. Cani is also interested in the endocannabinoid system. What is it? ‘Almost all our cells produce bioactive lipids. Some of these substances have effects similar to those of cannabis. They’re involved in regulating appetite and inflammation and in intestinal transit. My hypothesis is that this endocannabinoid system, especially in adipose (fatty) tissue, also communicates with the microbiota and that intestinal bacteria can order this system to store or burn fat.’
While promising, the field is in its early stages. ‘We’re only beginning to establish the link between the microbiota and certain diseases’, Prof. Cani cautions. ‘Many questions remain. For example, we haven’t come close to studying all the species of intestinal bacteria; 70 to 80% have never been grown. So no one can say what makes up a healthy microbiota, which might guard against obesity and related metabolic disorders. That’s the challenge for fundamental research: trying to understand how it all works.’ So that we might one day discover new treatments.
Prof. Cani’s research is or has been funded mainly by the FNRS, the WELBIO Institute, the European Research Council (ERC), the Crédit InBev-Baillet Latour and the Fondation Saint-Luc.
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