Intestinal microbiota, obesity and overweight: proven close links

Recent scientific research suggests that intestinal flora may play a role in the development of obesity, although all the mechanisms are not yet understood. However, early studies indicate that modifying the microbiota could help prevent this chronic disease and its cardiovascular complications, offering hope to those affected.

The intestinal microbiota, made up of more than 100,000 billion microorganisms, mainly bacteria, resides in the digestive tract and plays a crucial role in health. It provides various beneficial functions, such as the production of vitamins, the breakdown of compounds resistant to the action of human digestive enzymes, and the prevention of infections by acting as a barrier against harmful microbes. Researchers now consider it as an organ in its own right. Over the past fifteen years, using modern gene sequencing techniques, scientists have identified more than 1,000 different bacterial species belonging to four major families: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Its composition varies considerably from person to person. Numerous scientific studies indicate that an unbalanced or poorly diversified microbiota could contribute to the development of various conditions such as inflammatory bowel disease (IBD), type 2 diabetes, allergies, and neurodegenerative disorders. In addition, overweight, obesity, and their complications are also linked to this imbalance.

Links between microbiota composition and excess weight

The impact of microbiota composition on overweight or obesity is well documented. Preliminary studies on laboratory rodents have shown that transferring the microbiota from obese mice to lean mice makes them obese in less than a fortnight. Conversely, obese mice “endowed” with the microbiota of lean mice quickly lost weight and fat mass.

In humans, an initial study carried out by a team of American researchers in 2006 observed a disparity in the composition of the microbiota between obese adults and lean adults, with fewer Bacteroidetes and more Firmicutes in the former. Although some subsequent work does not confirm these results, recent research from Denmark and France reveals that 20 to 40% of overweight or obese adults (up to 50% in cases of severe obesity) have a poorly diversified microbiota. . In the Danish study, individuals with a poor microbiota gained more weight over the 9 years of follow-up compared to those with a richer microbiota. Scientists are currently focusing on key bacteria, including Akkermannia muciniphila, whose presence in large quantities is associated with improved microbiota diversity in obese adults.

In the case of children, several studies have established a link between excess weight and the composition of the microbiota during the first months of life. For example, a cohort of more than 11,500 children born in the United Kingdom and monitored for 7 years showed that taking antibiotics during the first 6 months of life was associated with a significant increase in mass index. body between 10 months and 3 years. These drugs, which aim to eliminate harmful germs, also destroy part of the microbiota, and their repeated use seems to permanently alter its composition. In another cohort of 552 Norwegian children monitored for 12 years, the composition of the microbiota at age 2 was correlated with body mass index at age 12: a low proportion of Bacteroides or Bifidobacterium seemed to predict overweight within a few years. years later. In addition to antibiotic treatments, the variations observed in the composition of the microbiota can be explained by the mode of delivery (births by cesarean section being considered unfavorable) or by diet (breastfeeding appearing to protect against obesity).

What is the link between weight gain and the composition of the microbiota?

Various hypotheses are put forward to explain how bacteria in the microbiota could influence weight gain.

First of all, the digestion by certain bacteria of the microbiota of fibers or carbohydrates not broken down by human digestive enzymes leads to the production of fatty acids (fats) which are assimilable. A high proportion of these bacteria leads to a notable increase in assimilated calories.

Studies in rodents and humans show that certain bacteria can influence the expression of genes regulating the storage or burning of reserve fat.

In addition, certain bacteria in the microbiota interfere with the intestinal production of hormones that regulate feelings of hunger, satiation and satiety. For example, incretins calm hunger while ghrelin whets the appetite. An imbalance in the microbiota can lead to abnormal feelings of hunger, thus promoting overconsumption of calories.

In rodents and humans, an imbalance between Firmicutes and Bacteroidetes is associated with an increased capacity for assimilation of calories in the jejunum (part of the small intestine). Recent research has also observed an increase in the assimilation possibilities of the jejunum in obese adults.

How can we act on the composition of the microbiota to prevent or treat obesity?

Obesity is a chronic disease that is very complex to treat due to its multiple factors. Despite initial promises, several drugs have been abandoned due to lack of proven effectiveness. Restrictive diets are not a viable solution because they are often followed by weight regain, thus making the situation worse. The best approach to stabilizing weight remains a balanced diet combined with regular physical activity. However, recent research on the impact of the gut microbiota offers new hope for innovative therapeutic treatments.

Recent knowledge suggests that a modification or enrichment of the microbiota of the people concerned could play a role in the prevention or treatment of overweight and obesity. Since diet appears to be a determining factor in the composition of the microbiota, various intervention studies have evaluated the effect of supplementation with prebiotics or probiotics, as well as that of an overall rebalancing of the diet.

Addition of prebiotics

Prebiotics are defined as compounds resistant to degradation by human digestive enzymes (similar to fiber), whose regular consumption stimulates the growth or activity of certain bacteria. Among the most studied, we find inulin and fructo-oligo-saccharides, available in the form of food supplements but also present in certain foods such as garlic, artichoke, asparagus, banana, chicory, onion, leek, salsify and rye.

Their regular consumption leads to an increase in the proportion of Bifidobacterium or Lactobacillus in the microbiota. In recent years, they have been tested on small samples of healthy, overweight, obese or diabetic people, with encouraging results: reduction of the feeling of hunger and improvement of satiety (by modulation of the intestinal hormones involved), reduction of inflammation and LPS blood levels, reduction of insulin resistance and even loss of fat mass. However, their mechanisms of action are not yet fully understood and, given that they are fermented by certain bacteria in the microbiota, they can cause digestive disorders. Researchers from the University of Montreal (Canada), who recently reviewed existing studies, believe that it is necessary to conduct larger-scale studies in order to confirm their effectiveness and determine optimal doses. Until more is known, it is recommended to regularly consume natural sources of these prebiotics, which provide many other beneficial nutrients such as fiber and antioxidants.

Addition of probiotics

Probiotics are microorganisms that reach the intestine alive and have a beneficial effect on health. They are available in the form of fermented milks or food supplements. The analysis of 15 studies carried out in humans with various strains of Bifidobacterium or Lactobacillus shows that in 85% of cases, they make it possible to lose weight or fat mass compared to a placebo. In a study of obese children, they increased incretins (intestinal “appetite suppressant” hormones) and reduced hepatic steatosis (fat accumulation in the liver). However, in rare cases, certain strains of Bifidobacterium or Lactobacillus can cause weight gain. Other bacteria are currently being studied. Professor Cani’s team (University of Louvain, Belgium), which has been working on the intestinal microbiota since the early 2000s, published a pilot study in 2019 using Akkermannia muciniphila. Overweight or obese adults with insulin resistance who received the bacteria saw their insulin resistance and levels of inflammation decrease. In three months, they lost on average 2.2 kilos, 1.4 kilos of body fat and 2.6 cm in waist size. French researchers from the Inserm unit in Rouen have developed a food supplement based on Hafnia alvei, a bacteria producing a protein improving the feeling of satiety. In hyperphagic obese mice, this bacteria reduced the quantity of food ingested, weight gain, fat mass and blood sugar levels. So far, no clinical studies in humans have been published, but overweight people who tested it reported a reduction in their appetite.

Ultimately, regular ingestion of certain probiotics could positively influence the microbiota and promote weight loss. It remains to be precisely determined the strains of bacteria and effective doses, because their effectiveness can vary from one person to another depending on the composition of their microbiota. These microorganisms do not necessarily establish themselves in the digestive tract, so regular treatments are necessary to maintain their effect. In addition, probiotics are not recommended for children or adults suffering from an immune deficiency, whether congenital, linked to an illness (lymphoma, leukemia, etc.) or to medical treatment (immunosuppressant, corticosteroid, chemotherapy, etc.). .).

Diet change

The effect of a change in diet was evaluated in the French MicroObese study. A moderately restrictive diet (1,200 to 1,500 kcal per day), rich in protein, fiber and slow-absorbing carbohydrates, led to a 30% increase in bacterial diversity in individuals with a low diversity microbiota. However, after 6 weeks, this change did not reduce insulin resistance or blood triglyceride levels as much as in the group whose microbiota was diverse at the start.

In general, the analysis of various diets and their associated microbiota shows that the diet most favorable to a diversified microbiota corresponds to a traditional diet, rich in varieties of plants, fresh and dried fruits and vegetables, whole grains, and low in meat, animal fats and ultra-processed industrial foods. In addition to its impact on the microbiota, such a diet is beneficial in containing obesity and its complications. Plant fibers reduce the feeling of hunger, the glycemic index of meals, and the blood level of LDL-cholesterol. Their numerous antioxidants, vitamins C and E, carotenoids, polyphenols, contribute to cardiovascular prevention.

Thus, various studies demonstrate that the intestinal microbiota can contribute to the development of obesity. Modulating its composition is one of the therapeutic options, but this is probably not enough to control this multifactorial disease. Progress still needs to be made to determine the ideal composition of the microbiota