What if health was more than genetics? What if it was everything we’re exposed to? The exposome represents the sum of all environmental, behavioral, and social factors that influence our biology from conception to death. In this playlist, experts explore how the exposome connects our microbiota, environment, lifestyle, and emotions; offering a new way to understand and prevent chronic diseases. From endocrine disruptors and stress to nutrition, integrative medicine, and early-life exposures, discover how these factors interact to shape health across a lifetime.

Dive into this series to better understand the science behind the exposome and how small, informed changes can make a big difference for global health

How can we avoid harmful exposures to our health?

Modern life is convenient but not always healthy. In this video, discover how everyday choices around food, lifestyle, and environment shape our long-term well-being and the health of future generations.

Through the lens of the exposome, this talk reminds us that true prevention starts with common sense habits: eating real, minimally processed food; moving daily; protecting mental health; and living more consciously for ourselves and for the planet.

You’ll learn:

• How modern habits and ultra-processed food impact health and inflammation
• Why balance, simplicity, and mindful consumption matter
• How early childhood and parenting shape lifelong resilience

Environmental & integrative medicine: a new way of healing?

Modern healthcare is evolving, moving beyond symptoms to explore how our environment, lifestyle, and mind-body balance influence chronic diseases.

This video explains how environmental medicine (understanding our exposures) and integrative medicine (combining evidence-based non-drug approaches) work together to improve prevention and patient outcomes.

You’ll learn:

• What environmental and integrative medicine mean in today’s healthcare
• The science behind validated non-drug practices: nutrition, activity, hypnosis, meditation, and acupuncture
• How these approaches support cancer, diabetes, obesity, and other chronic conditions

Exposome & health: does gender make a difference?

From hormone disruptors to occupational exposures, gender shapes how we interact with our environment and how it impacts our health.

In this video, discover how endocrine disruptors can influence the development of hormone-dependent cancers, early puberty, and reproductive disorders, and why understanding gender-specific exposures is key to protecting future generations.

You’ll learn:

• How endocrine disruptors impact men, women, and children differently
• Real-world examples: cosmetics, construction, farming, and beyond
• Why the exposome must include gender to advance precision prevention

Genome, epigenetics, exposome: how are they different?

Your genes are not your destiny. This video breaks down how genome (your DNA), epigenetics (how gene expression is switched on/off), and the exposome (the totality of life-long exposures) interact to shape health.

From DNA methylation and histones to endocrine disruptors, the microbiota, and windows of vulnerability (like the first 1,000 days), discover how environment and lifestyle orchestrate biology—and why prevention starts with understanding exposures.

You’ll learn:

• Clear definitions: genome vs. epigenetics vs. exposome
• How exposures modulate genes and drive low-grade inflammation
• Practical takeaways to reduce harmful exposures

How to introduce the exposome in consultation?

What if the key to understanding chronic diseases lies in everything we’re exposed to, from stress and diet to pollution and lifestyle?

In this video, Dr. Véronique Mondain, an infectious disease specialist, explains how studying the exposome — the sum of all environmental and behavioral exposures — transforms the way we approach prevention and integrative medicine.

Roughly one in six Chinese adults over 60 experience mild cognitive impairment (MCI) (sidenote: Mild Cognitive Impairment (MCI) MCI is a clinical stage between the expected cognitive decline of normal aging and the more severe decline of dementia. Individuals with MCI have noticeable memory or thinking problems but can still perform most daily activities, representing a critical window for intervention and study. ) , with an annual risk of progression to dementia of 6 to 15% (10 times higher than in people without MCI). How can we act at this stage? Through diet, according to a study that assessed how the inflammatory potential of the diet affects the diversity and composition of the oral and gut microbiota, as well as cognitive performance, in 54 Chinese adults over 60 (36 with MCI and 18 controls without).

Diet affects oral diversity

Oral microbiota diversity varies according to the dietary inflammatory score (measured by the E-DII (sidenote: E-DII score (Energy-adjusted Dietary Inflammatory Index) An epidemiological tool designed to assess an individual’s overall dietary inflammatory potential by adjusting this score according to total caloric intake, allowing standardized comparison between individuals regardless of energy consumption. ) ); oral microbial richness (measured by the Shannon index) decreases as the inflammatory potential of the diet increases.
However, the inflammatory score does not seem to significantly affect gut microbiota diversity.

Altered microbiota

Microbiota composition also changes. In individuals with an anti-inflammatory diet (tertile T1), the oral abundance of certain bacteria increases ¹. Among those following pro-inflammatory diets (T3), the most enriched taxa belong to the genus Lacticaseibacillus.
As for the gut microbiota, two taxa (the family Porphyromonadaceae and its genus Porphyromonas) were more abundant with a pro-inflammatory diet, while some bacteria (including the genera Haemophilus, Holdemanella, and norank.RF39) show reduced abundance.

Predicting cognitive decline?

Distinct oral and gut microbiota profiles could indicate the onset of disorders. Artificial intelligence models can predict mild cognitive impairment based solely on these microbiota, with moderate accuracy for the oral microbiota (AUC (sidenote: AUC (Area Under the Curve) A measure of a model’s ability to correctly distinguish between two classes (for example, “diseased” vs “healthy,” “positive” vs “negative”). It represents the area under a curve that plots the true positive rate (sensitivity) on the y-axis against the false positive rate on the x-axis. If the AUC equals 1, the model performs perfectly; above 0.80 it is generally considered very good, and above 0.90, excellent; at 0.5, it performs no better than random chance.
  ) = 0.75) and high accuracy for the gut microbiota (AUC = 0.87).

Vegetables, fruits, nuts, olive oil, fish... the Mediterranean diet, known for its many benefits, could have one more advantage: slowing cognitive decline.
That is what a study ¹ of 54 Chinese seniors with or without mild cognitive impairment (sidenote: Mild Cognitive Impairment (MCI) MCI is a clinical stage between the expected cognitive decline of normal aging and the more severe decline of dementia. Individuals with MCI have noticeable memory or thinking problems but can still perform most daily activities, representing a critical window for intervention and study. ) suggests. The study explored the effect of anti-inflammatory diets (sidenote: Anti-inflammatory diets Diets characterized by high consumption of fruits, vegetables, whole grains, legumes, fatty fish, nuts, olive oil and phytochemicals, while limiting the intake of foods with potentially pro-inflammatory properties such as red meat, refined carbohydrates and alcohol. The rationale for anti-inflammatory diets (including but not limited to the Mediterranean diet) lies in their capacity to decrease inflammation.

Source: Yu X, Pu H, Voss M. Overview of anti-inflammatory diets and their promising effects on non-communicable diseases. Br J Nutr. 2024 Oct 14;132(7):898-918. doi: 10.1017/S0007114524001405.  ) , in particular the Mediterranean diet.

When your plate calms inflammation and boosts cognition

The researchers observed that people who follow an anti-inflammatory diet have a more diverse population of oral bacteria, including a higher number of certain “good bacteria” such as Corynebacterium or Eubacterium yurii.
In return for the shelter and food we provide, these bacteria offer major benefits: they produce butyrate, for example, a compound that calms inflammation, protects the brain and supports memory. The same applies to the gut: the microbiota of people consuming anti-inflammatory diets hosts specific bacteria. 
Result of this mouth–gut–brain interconnection: higher cognitive scores on memory, attention and language tests among people who follow anti-inflammatory diets!

When your plate sparks inflammation, your brain takes the hit

In contrast, fans of diets high in saturated fat and low in fruits and vegetables (in short, pro-inflammatory diets) showed a decrease in oral bacterial diversity.

Less friendly bacteria such as Lacticaseibacillus took over. The problem: some of them are known to produce acids that cause cavities and trigger systemic inflammation, a factor linked to cognitive decline.
The same goes for gut microbiota: inflammatory diets promote bacteria associated with lower cognitive performance and weaken the microorganisms that could have boosted it.

Result: unimpressive cognitive scores for lovers of junk food!

Doctors treating endometrial cancer often focus on surgery, hormones, and tumor grade. But what if the microbes living in a patient’s body are quietly shaping how she feels, her stress levels, digestion, and even sexual interest? A new study from researchers at the University of Oklahoma turns that question into data ¹. They followed 140 women scheduled for hysterectomy, some with endometrial cancer (EC, n=47), others with benign gynecologic conditions such as fibroids or endometriosis (n=93).

Before surgery, each woman completed validated surveys assessing mental and physical health, GI symptoms, stress, sexual function, and vaginal comfort. At the same time, scientists collected vaginal and rectal swabs for microbiome sequencing. The goal: connect quality-of-life metrics to microbial fingerprints across two key body sites.

The microbial paradox of endometrial cancer

Here’s where things got surprising. In most healthy women, low vaginal diversity, dominated by protective Lactobacillus crispatus species, is considered a sign of balance. But in this study, endometrial cancer patients showed the opposite pattern: they had higher vaginal microbial diversity (sidenote: Vaginal microbial diversity Refers to the variety and balance of bacterial species living in the vagina. Changes in this diversity can influence symptoms like dryness, irritation, and infection risk.
  ) , and the more diverse their microbiome, the worse their vaginal dryness and irritation. Even more unexpected, Lactobacillus iners (sidenote: Lactobacillus iners A less protective vaginal bacterium that produces only L-lactic acid, often associated with microbial imbalances and vulnerability to opportunistic infections ) , often thought of as not very “friendly”, was enriched in women reporting worse symptoms, alongside Lactobacillus gasseri, and Streptococcus agalactiae, a rather “friendly” vaginal bacteria. In short, microbes that normally spell health appeared to coincide with discomfort in this cancer population, suggesting that the rules of vaginal ecology may shift under oncologic conditions.

Rethinking the role of microbes in cancer care

What makes this study stand out is its integration of patient experience with molecular biology, a rare bridge between the clinic and the lab. Rather than viewing the microbiome as a passive bystander, the data suggest it may be an active participant in symptom expression and recovery. In the future, mapping these microbial patterns could help predict which patients are most likely to struggle with vaginal or gastrointestinal side effects during cancer treatment, or whose emotional well-being might be at risk.

It also opens the door to precision microbiome interventions, from targeted probiotics to dietary strategies, designed not just to fight disease, but to restore comfort, intimacy, and resilience in women navigating endometrial cancer and its aftermath. As the lead authors put it, the microbes of the vagina and gut may soon become “vital signs” of how a woman feels, not just what disease she carries.

For decades, multiple sclerosis (MS) has been understood as a disease of the immune and nervous systems, a chronic battle of inflammation and neurodegeneration. But in recent years, evidence has been mounting that the gut microbiome may be a silent third player, influencing how patients respond to therapy, experience fatigue, and ultimately, how their disease evolves. Still, one question has remained unanswered: can gut microbes actually predict who will worsen?

A new longitudinal study from Laura Cox and Howard Weiner at Harvard Medical School, published in Cell Reports Medicine¹, brings us closer to that answer. Using the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) cohort, the team followed 192 people with MS over two years, pairing stool and serum metabolomics with MRI scans, cognitive tests, and quality-of-life data. Their goal was to find the microbial and metabolic fingerprints that appear just before patients transition from relapsing to progressive MS.

The missing microbes of stability

Among those whose disability worsened, several beneficial microbes had quietly disappeared. Eubacterium hallii, Butyricicoccus, and Blautia, all key producers of anti-inflammatory metabolites, were markedly reduced. In contrast, Alistipes onderdonkii and Bacteroides vulgatus expanded, tracking with higher MRI-detected brain atrophy and cognitive decline. Although these beneficial microbes are known to produce short-chain fatty acids (SCFAs) (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. ) like butyrate, the study found no change in SCFA levels. This implies that their role extends well beyond fiber fermentation. These species may shape immune and neural signaling through bile acid conversion, lipid modulation, and vitamin biosynthesis, a more complex and far-reaching mechanism than previously appreciated.

A clinical application?

Imagine adding microbiome screening to annual checkups for patients with relapsing-remitting MS - tracking the abundance of protective species or the loss of bile-acid producers as an early alert that the disease is changing course. This kind of “gut signature monitoring” could one day guide treatment intensity, rehabilitation planning, or nutritional interventions.
The therapeutic implications are equally compelling. If specific microbial metabolites, like vitamin B3, B6 derivatives, or secondary bile acids, act as neuroprotective agents, dietary supplementation or next-generation probiotics could restore that lost metabolic communication. The goal wouldn’t be to replace immunotherapy but to add a gut-targeted layer of neuroprotection (sidenote: Neuroprotection The preservation of neuronal structure and function against injury or degeneration. In the context of MS, neuroprotective strategies aim to prevent the loss of axons and myelin. The study suggests that certain microbial metabolites, such as vitamin B3, B6 derivatives, and bile acids, may exert neuroprotective effects, positioning the gut as a potential therapeutic target to slow disease progression. ) , helping patients preserve function longer.

In the coming years, as microbiome assays become cheaper and more standardized, it’s not hard to imagine a clinical future where neurologists, dietitians, and microbiome specialists work side by side, using microbial data to keep MS quiet, one gut metabolite at a time.
 

What is inside the probiotic coconut-based yogurt?

The coconut-based yogurt is made from organic coconut meat and coconut water, fermented with 16 custom probiotic strains, including Lactobacillus acidophilus, Bifidobacterium breve, and Streptococcus thermophilus.

What health benefits does it claim to offer? Is it truly beneficial for health?

It is reported online that consuming this yogurt may improve digestion, reduce bloating, promote healthier skin, and strengthen the immune system. While probiotics can offer health benefits, scientific evidence specifically supporting this yogurt’s claim remains limited.

We know that coconut flesh is mainly composed of lipids and such yogurt provides very little protein. On top of that coconut oil is used as a cure for all sorts of ailments, such as fighting viruses and bacteria, supporting immunity, reducing cholesterol, supporting thyroid function, and even weight loss ^1-4.

Coconut oil contains medium-chain triglycerides (MCT) fatty acids, which are more easily digested and less absorbed compared to longer-chain fatty acids. However, of all the saturated fatty acids in coconut oil, MCTs constitute only half. Some MCTs, such as lauric acid and capric acid, have antifungal and antiviral properties ^1-3, but the purpose of consuming food is to provide components that strengthen the immune system, which then fights microbes ⁴.

How does it impact the gut microbiota?

This probiotic-enriched yogurt contains live bacteria that can potentially influence gut microbiota. However, the effectiveness of probiotics depends on various factors, including the specific strains used, their ability to survive stomach acid, and the individual’s existing gut microbiome composition.

Some studies suggest that mediumchain triglycerides (MCTs), found in coconut, may affect microbiome composition. However, research on probiotic coconut-based products is still in its early stages. Moreover, while coconut oil contains antimicrobial compounds like lauric acid (converted into monolaurin in the body), this does not necessarily translate into overall gut health benefits ^{1, 3}.

An interesting rat study investigating different dietary oils’ effects on gut microbiota found that coconut oil consumption led to reduced bacterial diversity, increased markers of metabolic endotoxemia, fatty liver disease, and higher LDL cholesterol levels ⁵. While animal studies provide insight, further clinical trials in humans are needed to determine this probiotic-enriched yogurt’s actual effects on gut health.

From your dietary perspective, are these new probiotic products worth considering?

Remember that food is primarily intended to provide us with nutrients, vitamins and minerals. Coconut dairy, like yogurt, does not have high nutritional density ^{1, 3}.

While this probiotic-rich yogurt presents an innovative approach to delivering beneficial bacteria, its high-fat content, low protein levels, and cost should be considered when recommending it as a dietary option ^{2, 6}. Traditional probiotic-rich foods, such as yogurt, kefir, and fermented vegetables, provide similar benefits with a more balanced nutritional profile. A varied and balanced diet, low in processed foods and rich in vegetables, fruits, whole grains, and legumes, supports microbiome diversity.

Transgender women: a specific neovaginal flora

Some transgender women correct the gender incongruity of feeling like a woman in the depth of their being despite the physical presence of male genitalia and being referred to as a man by undergoing “penile inversion vaginoplasty.” In other words, by surgically transforming their penis into a vagina. However successful the surgery, the skin of this newly constructed vagina will combine skin from the penis and a skin graft from the scrotum and/or other area (s) (stomach, groin, etc.). How does this affect health? Vaginal microbiota makes a crucial contribution to good vaginal health in cisgender women.

And American researchers have now turned their attention to the intimate flora of transgender women undergoing surgery: might the composition of neovaginal microbiota explain certain problems, including the frequently reported issue of vaginal discharge? It is a question worth asking, and one that has now been answered thanks to a study comparing the vaginal microbiota of transgender women undergoing vaginoplasty with that of cisgender women. The results? They have very different microbiota. The vaginal flora of cisgender women is not very diverse and is dominated largely by lactobacilli, which creates an acidic environment that repels pathogens. That of transgender women has less than 3% of these precious allies and is much more diverse. Diversity in the vagina is not a sign of good health; quite the opposite. It is observed in cisgender women suffering from bacterial vaginosis, which increases risk of sexually transmitted infections (including HIV/AIDS) and miscarriage.

How is this new microbial ecosystem created? Or more precisely, which bacteria make up the neovaginal microbiota of transgender women having undergone surgery? They result no doubt from the flora of the skin (penis, scrotum, etc.) used during surgery. However, oral-genital and genital-genital transmission also appears to be involved. In fact, the neovaginal flora of transgender women having undergone surgery has been shown to include bacterial species typical not only of the skin and digestive tract, but also of the mouth. Since sexual relations influence the likelihood of a bacterium called E. faecalis, there is also genital transfer.

On the other hand, while the proliferation of protective lactobacilli in cisgender women can be explained by hormones, the hormonal status of transgender women (comparable to that of cisgender women due to treatment) seemed to make no difference. Further studies on larger numbers of transgender women will be needed to better understand their neovaginal health.

^{Winston McPherson G, Goldstein Z, Salipante SJ, et al. The Vaginal Microbiome of Transgender and Gender Nonbinary Individuals. Transgend Health 2024; 9: 205-11.}

Gut microbiota regulates insomnia-like behaviors via gut-brain axis

While sleep is known to be in bidirectional connection with the gut microbiota, the underlying mechanisms have been largely unknown. However, it seems that gut-derived metabolites can affect some behaviors in the host, such as anxiety-like behavior. Additionally, some clinical studies have reported alterations in the gut microbiota in individuals with chronic insomnia.

Wang et al. sought to clarify how the gut microbiota could shape sleep behavior. For this purpose, they studied sleepwake behavior in specific pathogen-free (SPF) and germ-free (GF) mice. GF mice are free of all microorganisms, including those that are typically found
in the gut, while SPF mice are free of a specific list of pathogens by routine testing The recording of 24-h ambulatory electroencephalogram (EEG)-electromyogram (EMG) showed that GF mice had decreased time of wakefulness and REM sleep compared to SPF mice. To identify specific metabolites that are involved in gut microbiota-mediated sleep-related behavioral changes, the authors studied feces and hypothalamus tissue samples using targeted metabolomics. It was found that gut microbiota-derived short chain fatty acid, butyrate was the most significant modulator of sleep behavior. Further, oral administration of tributyrin, a precursor of butyrate administration led to a significant 39.50% reduction of wakefulness and 77.99% increase in REM sleep. The underlying mechanism seems to be that tributyrin inhibits lateral hypothalamus orexin neuron activity.

By studying humans, the authors also observed a decrease in 39 butyrate producers in insomnia patients compared with controls. Ultimately, the authors also showed that GF mice that received microbiota from insomnia patients exhibited sleep disturbances, which were recovered by butyrate supplementation. To conclude, the study highlights the potential of butyrate as a therapeutic agent to mitigate sleep disorders.

^{Wang Z, Wang Z, Lu T, et al. Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis. Mol Psychiatry 2025; 30: 2597-611.}

Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis

Several pro-tumorigenic bacteria, such as genotoxic Escherichia coli (E. coli), and enterotoxigenic Bacteroides fragilis (B. fragilis), have been associated with the promotion of cancer metastasis. In addition, cytolethal distending toxin (CDT)-producing Campylobacter have been found to be enriched in tumor tissues compared to normal adjacent tissues. However, the connection between genotoxin-producing bacteria and cancer metastasis is poorly understood. The authors of this study obtained primary colorectal cancer (CRC) tissues from 34 chemotherapy-naive patients (TNM stage I and IIA) with distant metastasis within 3 years (metastasis group) and 37 patients who remained metastasis-free (non-metastasis group) during 3 years’ follow-up. They found a significant enrichment of Campylobacter in the metastasis group, and that the patients with intratumor Campylobacter had significantly poorer prognosis. They also confirmed their findings using a validation cohort and a publicly available database. CDT is the major virulence factor responsible for Campylobacter-mediated pathogenesis, and in the host cells it induces DNA damage and cell-cycle arrest. The metastasis group expressed more bioactive CDT subunit cdtB and Campylobacter invasion antigen B (ciaB), a virulence factor specific to C. jejuni. In vitro, C. jejuni significantly increased cell migration and invasion ability of various CRC cell lines. In one mice model, administration of C. jejuni increased migration and invasion ability as compared with controls, and in another it significantly increased liver metastasis. Altogether, these findings prove that intestinal C. jejuni promotes CRC metastasis. Interestingly, the pro-metastasis ability was attenuated in the absence of CdtB. Mechanistically, it seems that CDT activated JAK-STAT signaling pathway leading to expression of MMP genes and tumor metastasis.

^{He Z, Yu J, Gong J, et al. Campylobacter jejuniderived cytolethal distending toxin promotes colorectal cancer metastasis. Cell Host Microbe 2024; 32: 2080-91.}

Quiescent Crohn’s disease, sulfidogenic microbes and sulfur metabolic pathways: the functional consequences

In the quiescent inflammatory bowel disease, there is no active inflammation. However, the patients report persistent symptoms, especially with Crohn’s disease (CD). The microbiome is shown to be altered in quiescent CD patients with persistent symptoms (qCD + S). Specifically, the patients with qCD + S have been shown to have more sulfidogenic microbes and microbial gene pathways of sulfur metabolism. Nevertheless, the functional significance of these changes has remained unknown. In this multicenter observational study,
metagenomic shotgun sequencing and metabolomics profiling of the qCD + S patients’ feces were performed. Additionally, patient with active Crohn’s Disease (aCD), with quiescent Crohn’s disease without persistent GI symptoms (qCD-S) and with diarrhea predominant irritable bowel syndrome (IBS-D) were included and compared with qCD + S.

The authors report that fecal metabolites within cysteine/methionine, bile acid, and fatty acid pathways were among the most differentially abundant in qCD + S patients relative to other groups. The differences persisted even when inflammation, i.e., calprotectin levels were lower. Glycine, serine, and threonine; glutathione; and cysteine and methionine were the most enriched pathways in
qCD + S, and these are important sulfur metabolic pathways in the human gut. In addition to metabolites, many bacterial sulfur metabolic genes were dysregulated in qCD + S. By integrating the metagenomic and metabolomic datasets, the authors further found that taurine and hypotaurine; nicotinate and nicotinamide; cysteine and methionine; and glycine, serine, and threonine were the top metabolic pathways associated with the enriched microbes in qCD + S. AS elevated H2S concentrations inhibit mitochondrial
functions of the host, the results suggest links between microbial-derived metabolites and host mitochondrial function in patients with qCD + S. Altogether, the results of this study suggest that strategies to decrease sulfidogenic microbes and associated sulfur metabolic pathways could represent a novel strategy to improve quality of life in quiescent Crohn’s disease with persistent symptoms.

^{Golob J, Rao K, Berinstein JA, et al. Why Symptoms Linger in Quiescent Crohn’s Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways. Inflamm Bowel Dis 2025; 31: 763-76.}

Mechanisms

Microbiota includes a wide variety of bacteria, viruses, fungi, and other microorganisms which have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host. We often referred to it as a “hidden organ”.

When this ecosystem is disrupted (dysbiosis), it can contribute to a wide range of diseases - from gastrointestinal diseases to systemic metabolic and neurological disorders ¹.

At birth, the newborn’s gut is sterile, but it is rapidly colonized by microorganisms from the environment, including Enterobacteria, Enterococci, Lactobacilli, and Bifidobacteria. The gut microbiota undergoes dynamic and gradual changes from infancy to adulthood, shaped by various internal and external factors. These microbial shifts are critical for establishing a stable and resilient microbiome that supports health across the lifespan. In healthy adults, the gut microbiota is estimated to include over 1,000 species of bacteria. Importantly, this microbial community can influence drug pharmacodynamics by either directly metabolizing drugs or modifying the host’s metabolic and immune responses.

Orally administered drugs travel through the gastrointestinal (GI) tract, with their absorption and metabolism influenced at each stage. Drugs that are not completely absorbed in the upper GI tract may reach the colon. In turn, the gut microbiome actively participates in the chemical transformation of these drugs, affecting their pharmacokinetics, bioactivity, and potential toxicity.

Several mechanisms are involved by which drugs affect gut microbiota, including:

1 / direct effects (antibiotics can kill some species of microbiota, including both harmful and beneficial species, leading to imbalances
in gut microbiota);

2 / altered gut motility (particular drugs can slow down gut motility, which can lead to overgrowth of harmful bacteria);

3 / modulation of immune function (several drugs can interact with gut immunity which in turn can affect gut microbiota);

4 / changes in pH in the intestine (the pH balance plays a significant role in the gastrointestinal tract which affects the growth and survival of different types of species of gut microbiota. Some drugs can change the pH value of the gut, which affects the proliferation of different microbes, thereby affecting the overall composition of gut microbiota);

5 / interference with microbial metabolism (several drugs can interfere with microbial metabolism, which may have an effect on gut microbiota);

6 / dietary changes (certain drugs can change the dietary environment in the gut. This may influence gut microbiota by changing the availability of nutrients and other compounds that gut microbiota use to grow and survive) ^2-4.

Gut microbiome-drug interactions are shaped not only by microbial activity but also by host genetics, environmental exposures, and their interplay, posing a complex challenge for personalized therapy. Genome-wide association studies (GWAS) have identified human genetic variants, especially in genes related to immunity, metabolism, and digestion (e.g., C-type lectins and lactase) that influence gut microbiota composition.

The examples of irinotecan and cytochrome p450

Irinotecan, an anti-cancer medication, is reactivated in the gut by microbial enzymes causing severe diarrhea - a major side effect of the chemotherapy. Certain gut bacteria, particularly β-glucuronidase-producing species such as Escherichia coli, Clostridium and Bacteroides, produce enzymes that convert SN-38G back into its active form SN-38 in the intestine. This reactivation is toxic to intestinal
epithelial cells, causing mucosal injury, inflammation, and severe delayed-onset diarrhea ³.

The gut microbiome can profoundly influence the host’s drug-metabolizing enzymes, an emerging factor in personalized medicine. Cytochrome P450 enzymes, particularly CYP3A4, are modulated by gut-derived compounds. Short-chain fatty acids (SCFAs) can modulate enzyme gene expression through epigenetic mechanisms. Meanwhile, secondary bile acids interact with nuclear receptors like FXR, CAR, and PXR, altering drug metabolism ³.

Strategies for reducing the collateral damage of drugs on the microbiome ⁵

To protect the gut microbiome, one key strategy is to avoid drugs known to disrupt microbial balance whenever possible. Minimizing direct interaction between drugs and gut microbes can reduce negative effects. In contrast, restorative approaches aim to repair microbial communities after disruption. These include dietary interventions, probiotics, live biotherapeutic products, and fecal microbiota transplantation. Dietary interventions act as microbiota- targeted therapies. Dietary fibers, for instance, foster the growth of SCFA-producing bacteria, which are essential for immune function, epithelial development, and maintaining an anaerobic gut environment ⁵. Probiotics such as Saccharomyces boulardii CNCM I-745, Lactobacillus reuteri and Bifidobacterium spp. support colonization resistance, immune modulation, and gut barrier integrity. Postbiotics, composed of inactivated microbes or their components, also offer health benefits without requiring live organisms. Meanwhile, live biotherapeutic products represent a new category of medical interventions using live microbes specifically designed to treat or prevent disease, distinct from traditional supplements ³.

Restoring the microbial community involves more than simply recolonizing bacteria. It requires reestablishing a balanced ecosystem that supports immune, metabolic, and barrier functions. Strategies to protect the microbiome during drug therapy fall into two main categories: preventive approaches that minimize drug-induced disruption, and restorative approaches that aim to rebuild microbial diversity and function after damage has occurred ⁵.

Selecting the right strategy requires a precision-based approach, tailored to the drug, disease context, and patient. Success depends on a deep understanding of the ecological and biochemical principles that govern microbiota drug interactions. Ongoing research is essential to guide effective recovery and protection of the gut microbiome during and after drug therapy.