What is the link between Microbiota and Obesity ?

Microbiota

Obesity and microbiota

The WHO (World Health Organization) defines obesity as "an abnormal or excessive accumulation of fat that presents a risk to health".

In adults, it corresponds to a BMI (Body Mass Index) equal to or greater than 30, the BMI being calculated according to the following formula: Weight (kg) / Height (m).

Photo Natasha Spencer in Pexels

In children, the measurement of obesity is based on the child's age and on baseline data that take into account height and weight for a given age.

The calculation basis differs according to the age group, from 0 to 5 years and from 5 to 19 years.

The WHO has recognized obesity as a chronic disease since 1997.

Prevalence

According to the WHO, in 2016, worldwide, the prevalence of obesity was 13% of the population, representing 650 million people. Among children, it was 6% among girls and 8% among boys.

In 2019, according to INSERM (Institut National de la Santé et de la Recherche Médicale), obesity will affect 17% of adults and children, 16% of boys and 18% of girls2.

The global prevalence of obesity has tripled since 1975, and although obesity is not a contagious disease, the WHO reports a pandemic3.

Consequences

Obesity is a major risk factor for many chronic diseases4 :

• Type 2 Diabetes
• Hypertension
• Cardiovascular diseases: myocardial infarction, stroke, etc.
• Joint diseases, particularly osteoarthritis and musculoskeletal disorders
• Cancers5 : uterus, ovaries, breast in women; prostate in men; liver, kidney, colon, esophagus for both sexes.
• Sleep Apnea
• Depression, etc.

Causes identified

The classic causes identified for obesity are

• A diet too abundant and rich in carbohydrates and fats.
• The sedentary lifestyle
• A positive imbalance between calories ingested and calories expended as a result of the first two factors
• Stress
• A deregulation of the biological clock: insufficient sleep, irregular meals, night work
• Genetic (gene related) and epigenetic (altering gene expression without changing the gene) factors
• Viruses.
• Taking certain medications

The usual treatments

They are based on an adapted diet, physical exercise7 , certain medications and, in extreme cases, bariatric surgery that reduces the volume of the stomach and brings satiety more quickly.

The main techniques used are: gastric banding, longitudinal gastrectomy or "sleeve", stomach bypass, biliopancreatic bypass8.

The case of the gastric bypass is interesting because it has been shown that it is not the reduction in stomach volume that causes weight loss, but rather the modification of the microbiota after the operation.

Therefore, the microbiota is directly related to the prevalence of obesity.

What is the intestinal microbiota?

From "micro", which means "small" and "bio", "life", the microbiota is the set of microorganisms: bacteria, fungi, archaea, viruses, unicellular eukaryotes that live in the human host, mainly in its digestive tract, with a maximum concentration in the colon.

Microbiota weigh from 1 kg to 5 kg in adults, this weight being related to the type of food and not to the weight of the person10.

The microbiota contains 100,000 billion bacteria belonging to 1000 species. They are mostly anaerobic, that is, adapted to an oxygen-free environment. The microorganisms are 10 times more numerous than the cells of the human body.

Each bacterium has its own DNA. The accumulated DNA of the bacteria in the microbiota constitutes a metagenome, which contains 100 times more genes than the human genome.

The microbiota bacteria are divided into families or Phylae, whose indicative distribution in a healthy individual is as follows

• Firmicutes (64%): lactobacilli, streptococci, enterococci, clostridium.
• Bacteroidetes (23%): bacteria present in the environment, soil, water, sea water
• Proteobacteria (8%)
• Actinobacteria (3%).
• Verrucomicrobia, Fusobacteria, TM7 (2%).

The precise composition of the microbiota is specific to each individual, like an identity card. It is primarily conditioned by the mode of birth: vaginal or cesarean. In fact, during a vaginal birth, the microbiota is transmitted from mother to child by the vaginal flora.

The microbiota is also determined by a person's geographical origin, in the sense of "living environment". Finally, it evolves according to a person's age, eating habits and environment.

Roles

The microbiota has recently been considered an organ in its own right.

The microorganisms that make up the microbiota are either beneficial or "commensal" to their human host, in this case a mutually beneficial association; or "parasites". In this case, the microorganisms benefit from shelter and food without giving anything in return to the host, whether pathogenic, that is, harmful or even dangerous to the survival of the host.

The microbiota performs important physiological functions:

• Protective and barrier function against exogenous pathogens
• Digestion of nutrients (lipids, carbohydrates, proteins),
• The metabolism of gases,
• Synthesis of vitamins (B12, K)
• Maturation and modulation of the immune system, modulation of brain functions13,
• Intestinal motility,
• Detoxification of compounds of food origin,
• The metabolism of food, bioactive substances produced by the body and drugs.

Obese and non-obese people

In obese people, compared to those who are not, there is a decrease in the diversity of bacterial species, a decrease in bacteroids and an increase in firmicutes14 ¹⁵.

For some research teams16 , modification of the microbiota is believed to be the cause of obesity.

They demonstrated this hypothesis by transplanting the microbes of obese mice into lean axenic mice, i.e. without intestinal flora: the axenic mice that received the "obese" microbiota became obese, without any change in diet.

In addition, obesity is said to be "transmissible" from mother to child through microbiota .

The researchers propose three theories.

Theory of the energy mechanism

It is believed that some bacteria, equipped with specific enzymes, have a greater capacity to digest complex sugars that are not digestible by humans (fiber) and to produce mono- and disaccharides, sugars that are digestible by humans, from these fibers.

This would increase the energy production of the alimentary bolus in obese subjects.

The inflammatory theory

Some intestinal bacteria have pro-inflammatory molecules called lipopolysaccharides or LPS on their surface.

LPS would participate in the inflammatory processes through the following mechanism:

The small intestine can be damaged by multifactorial causes (diet, alcohol, contaminants, stress, etc.) and become too permeable, which is called "filtering intestine syndrome" or "porous intestine syndrome" or "intestinal hyperpermeability".

In case of intestinal hyperpermeability, the LPS would pass from the small intestine into the blood and generate an antibody/antigen type inflammatory reaction. The immune system, through T-lymphocytes, attacks the LPS, creating a so-called "low-grade" inflammation.

The molecules circulating in the blood, called cytokines, are produced during these inflammatory reactions19. 19 LPS circulating in the bloodstream causes inflammation in fatty tissue.

Regulation of adipose tissue composition

LPS in the blood increases insulin secretion, through mechanisms that are not fully elucidated.21 21 Insulin is a hormone that reduces blood glucose levels by "moving" glucose into cells.

In adipocytes, glucose is metabolized and stored as triglycerides. It is as if the bacteria in the microbiota help their host store calories in their fat tissue for later use (to the benefit of the bacteria).²²

Complications

The "obesity-like" microbiota is also believed to be responsible for the complications of obesity23 .

Type 2 Diabetes

Hyperinsulinemia (too much insulin in the blood) causes insulin resistance. The insulin receptors on the cells no longer respond to insulin and the cells no longer allow glucose to enter.

The result is that the cells no longer have enough glucose to produce energy and the glucose builds up in the bloodstream where it has toxic effects.

Atherosclerosis and cardiovascular diseases

A high level of bacterial fragments and metabolites circulating in the blood, also known as endotoxemia, is associated with inflammation, one of the triggers of atheromatous and cardiovascular diseases24.

Cancers

Endotoxemia and low-grade inflammation play a role in tumor initiation, while hyperinsulinemia promotes the growth of cancer cells25.

An adapted diet

The diet, which promotes a balanced microbiota and combats obesity, is based on the following principles :

Reduce saturated fats: meat, fatty deli, cheese, fried foods, cakes, sauces, chocolate

Reducing trans fats: hydrogenated margarines, milk and derived products ;

Limit the consumption of corn, sunflower, grape seed, nut or soybean oils, which are rich in unsaturated fatty acids of the omega-6 series.

Avoid quick sugars: sugar, soft drinks, honey, sweets, white bread, potatoes, white pasta, white flour, white rice, especially sushi and risotto rice;

Favour unsaturated fatty acids, especially those of the omega-3 series: rapeseed oil, linseed oil, camelina oil, walnut oil, fatty fish.

Increase the consumption of plants, vegetables and fruits rich in complex carbohydrates, especially those with prebiotic activity, i.e. that serve as "food" for the microbiota27 : leeks, onions, garlic, asparagus, artichokes, parsnips, Jerusalem artichokes, chicory.

Eat foods rich in polyphenols: red berries, pomegranate, red apples, red grapes, red onions, green tea, soy, cocoa, etc.

However, adherence to these dietary principles does not always lead to lasting weight loss in obese people.

Action of probiotics

According to the WHO, probiotics are "living microorganisms that, when ingested in sufficient quantities, produce beneficial health effects in those who consume them.

The best known probiotics are lactobacilli and bifidobacteria, present in lactofermented foods such as yogurt, sauerkraut, kefir and kimchi.

Probiotics are able to influence the weight of individuals in both directions. In fact, some probiotics can promote growth and cause weight gain, which is one of their applications in poultry farming28.

In addition, probiotics to combat obesity have been the subject of numerous studies and some applications29 :

Lactobacillus plantarum, Lactobacillus acidophilus and Lactobacillus casei strains appear to be effective in the treatment of obesity, hyperlipidemia and related metabolic disorders.

Lactobacillus gasseri is a gram-positive anaerobic lactobacillus.

L. gasseri strain SBT2055 is believed to have antiobestive and anti-inflammatory effects. It would reduce the size of adipocytes. However, only after a certain size the adipocytes secrete pro-inflammatory cytokines.

This phenomenon could be explained by the unfavorable action of L-gasseri on the hydrolysis of fats in the intestine by pancreatic lipase, an enzyme produced by the pancreas and released in the intestine, whose function is to hydrolyze dietary fats.

There are several dietary supplements containing L-gasseri on the market. Here is a non-exhaustive list of the laboratories that market these nutritional supplements: Supersmart, Copmed, Vit All+, Cell Innov, AraganClasseri, etc.

• Akkermansiamuniciphila (Verrucomicrobia) is a Gram-negative bacteria.

Akkermansiamuniciphila is present in smaller quantities in obese people. It plays a role in intestinal permeability, reduces inflammation and has positive effects on insulin resistance and dyslipidemia33.

The commercialization of food supplements based on A. municiphila is being developed.

• Saccharomyces cerevisiae var. boulardii, Enterobacter halii are other strains under study that offer interesting potential in the fight against obesity.

In conclusion, the use of probiotics to modulate the microbiota is a developing strategy that seems promising in the fight against obesity. However, lifestyle modification, through diet and exercise, remains inevitable.

Stool transplantation

Fecal transplantation consists of implanting the microbiota of a healthy person into the intestine of a sick or obese person. This technique is performed through a nasojejunal tube: the healthy microbiota from the donor is introduced directly into the small intestine of the recipient.

Stool transplantation is only authorized and practiced in case of recurrent colitis with clostridium difficile, a pathogenic and antibiotic-resistant bacteria that causes severe diarrhea.

The role of the microbiota is fundamental to the understanding and treatment of obesity and its complications.

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