Microbiota and exposome: a dialog at the core of our health

The problem is that many features of the external exposome (low-fiber or high-fat diet, emulsifiers, heavy metals, phthalates, microplastics, fine air particles, pesticides, environmental pollutants, stress, etc.) can upset the balance of our microbiota and lead to dysbiosis. 

We know that dysbiosis is linked to numerous chronic diseases, such as obesity, type 2 diabetes, asthma, chronic inflammatory bowel disease, autoimmune diseases, depression, and cerebral development disorders ¹. 

Collapse of biodiversity = microbiota and health at risk

This ticking time bomb has been confirmed by international expert group IPBES : biodiversity is “declining globally at rates unprecedented in human history” ¹³ . This collapse is the result of global warming, over-exploitation of land, and pollution. 

That’s a problem for our microbiota, since fewer animal and plant species means less microbial diversity in ecosystems and therefore more alteration of microbiota-mediated immunomodulatory circuits, as well as more allergies and autoimmune diseases ¹⁴. 

According to the World Allergy Organization, the loss of biodiversity results in reduced interaction between environmental and human microbiota, which can lead to immune dysfunction and impaired tolerance mechanisms ¹⁵. 

On the other hand, we’ve known since 2005 that microbe-rich environments (living on a farm, close to nature, etc.) are associated with protection against immune diseases. 

Fungal exposome: regulating the immune response

The microbiota, whether in the gut, vagina, lungs, or on our skin, comprises not only bacteria, but also viruses, archaea... and fungi. The fungal “mycobiota” is essential to the balance and stability of our microbiota. Numerous studies on infants have shown the microbiota fungal composition to be associated with the risk of developing an allergic disease. 

We now know that the mycobiota largely depends on the fungal exposome. Analyses of fungal taxa have shown that the fungi most frequently found in the gut, mouth, lungs, and on the skin are the same as those found in the environment, whether indoors (walls, furniture, indoor air, etc.) or outdoors (food, water, soil, etc.).  

Fungi present everywhere in the environment may therefore come into sustained contact with our organism, modulating our immune responses.

Drugs, exposome, microbiota: a delicate balance  

As part of our exposome, drugs interact in complex ways with the gut microbiota, influencing both its composition and functions. 

Take, for example, common treatments such as proton pump inhibitors (PPIs), used to treat gastroesophageal reflux disease. PPIs modify the acidic environment of the stomach, allowing oral bacteria to reach the gut. This can influence the microbial ecosystem by favoring the growth of certain strains. These changes are associated with an increased risk of infection, such as those caused by Clostridium difficile, but can be controlled through appropriate use (avoiding long-term treatment where possible) and medical follow-up ²⁰.  

The  microbiota is no mere bystander. It plays an active role in the processing of drugs. 

For example, gut bacteria can improve the efficacy of metformin (an anti-diabetic drug) by stimulating the production of short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) (SCFAs) beneficial to health. 

Conversely, in rare cases, the  microbiota can transform active molecules into toxic compounds, as in the case of brivudine, a now-banned antiviral used to treat shingels, which gut microorganisms can convert into liver-toxic bromovinyluracil.

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