While food additives (sidenote: Food additives Food additives are substances primarily added to processed foods, or other foods produced on an industrial scale, for technical purposes, e.g. to improve safety, increase the amount of time a food can be stored, or modify sensory properties of food.  Source: World Health Organization )  improve the texture and shelf life of many foods, they also raise health concerns. Some are suspected of promoting chronic inflammatory diseases by acting directly on our gut microbiota.

Nevertheless, the effects vary widely from one individual to another, according to a previous randomized controlled trial in humans (FRESH study: acronym for Functional Research on Emulsifiers in Humans). The additive used: carboxymethylcellulose (sidenote: Sodium carboxymethyl cellulose Sodium carboxymethyl cellulose (or cellulose gum, E466) is a food additive with multiple functional properties: firming agent, coating agent, bulking agent, emulsifier, thickener, gelling agent, humectant, stabilizer, etc. Its use is authorized in a wide range of products from dairy products (creams, fresh or processed cheese, dairy desserts, etc.) to cooked fish, from ice creams to dried or canned vegetables, from confectionery to breakfast cereals, from certain meats or fish to mustards and soups, from appetizers to beer or certain spirits, and so on. Source: Food and Agriculture Organization of the United Nations   ) (or E466).

How can this sensitivity be explained or even predicted? The team ¹ has continued its previous work by focusing on the microbiota. Their in vitro demonstration used a mini laboratory reactor capable of mimicking the human gut microbiota.

The reactor predicts sensitivity or resistance

When the researchers exposed the microbiota collected from the FRESH study volunteers to carboxymethylcellulose in the bioreactor, they found the same difference in sensitivity as observed in vivo in the FRESH trial: the microbiota of the same 2 of the 7 volunteers exposed to E466 were disturbed when exposed to the emulsifier.

In other words, the microreactor faithfully reproduces the variations between individuals observed in the FRESH trial, making it possible to predict whether a given microbiota is sensitive to E466, without the need for in vivo studies..

Transplanted flora transmit sensitivity to mice

To confirm that this intestinal flora was responsible for the intestinal inflammation observed in some FRESH trial subjects exposed to E466, the microbiota of 2 E466-"sensitive" individuals and 2 non-sensitive individuals were transplanted into flora-free mice.

Only mice given the "sensitive" flora and exposed to the additive developed intestinal inflammation and severe colitis:

• shortening of the colon
• damage to the mucosa
• macrophage infiltration 

Certain bacteria, including Adlercreutzia equolifaciens and Frisingicoccus caecimuris, were associated with this inflammation.

Emulsifiers, texturizers, preservatives, colorants: food additives (sidenote: Food additives Food additives are substances primarily added to processed foods, or other foods produced on an industrial scale, for technical purposes, e.g. to improve safety, increase the amount of time a food can be stored, or modify sensory properties of food.  Source: World Health Organization )  which are very common in ultra-processed products, have invaded our cupboards. These include E466, or carboxymethylcellulose (sidenote: Sodium carboxymethyl cellulose Sodium carboxymethyl cellulose (or cellulose gum, E466) is a food additive with multiple functional properties: firming agent, coating agent, bulking agent, emulsifier, thickener, gelling agent, humectant, stabilizer, etc. Its use is authorized in a wide range of products from dairy products (creams, fresh or processed cheese, dairy desserts, etc.) to cooked fish, from ice creams to dried or canned vegetables, from confectionery to breakfast cereals, from certain meats or fish to mustards and soups, from appetizers to beer or certain spirits, and so on. Source: Food and Agriculture Organization of the United Nations   ) , which is used in industrial ice creams and buns. The problem: several studies have alerted us to its potentially harmful effect on our intestinal and metabolic health.

A recent study ¹ also points out that the composition of our microbiota could be altered by repeated consumption of this type of emulsifier. In a clinical trial previously carried out on healthy volunteers (7 consuming E466, and 9 controls not consuming it, for comparison), researchers had shown that people’s responses to this additive differ: some people are sensitive, and their gut microbiota is disrupted, while others are resistant and their flora remains unaffected.

This difference is explained by the microbial composition in our gut, according to the latest studies by the same researchers. In other words, your flora predicts whether you're one of the lucky ones who digest fluffy industrial buns without a care in the world or one of those people who react badly to E466!

The gut microbiota predicts... and transmits!

To understand these differences, the researchers used a mini laboratory reactor capable of mimicking the human microbiota and testing the effect of E466 on different microbiota in vitro, in this case using the stools of the 7 volunteers from the previous study. And the experiment was a success! Only the stools of the sensitive patients hyper-reacted to the food emulsifier E466, making it possible to identify sensitive patients. This new approach could eventually allow us to predict the microbiota's response to certain emulsifiers.

What's more, sensitivity to the effects of E466 has been shown to be transmissible to mice, via fecal microbiota transplants. Flora from volunteers who are sensitive to E466 cause severe colitis in animals who consume the emulsifier, illustrating possible direct health consequences. These results also show the extent to which the bacteria in our microbiota can play an active role in the inflammatory response to certain additives.

A signature requiring refinement

It remained to be seen whether analyzing the DNA of the stool bacteria cocktail alone would be sufficient to predict sensitivity to E466. The researchers trained an algorithm to identify differences between the stool DNA of sensitive and non-sensitive volunteers. Results: 78 markers were counted. These bacterial markers, present in the microbiota of certain individuals, could predict sensitivity to emulsifiers. But this signature is not yet perfect: it worked in the clinical trial cohort, but its application to subjects from other studies has not yielded the expected results. Further studies are needed to validate this signature in wider populations.

While we wait for a universal signature that could facilitate screening, and thus avoid intestinal disorders in sensitive individuals, perhaps it's time to start cooking from scratch at home, especially since additives may also contribute to behavioral disorders. Not to mention microplastics in takeaway food packaging. We can't stress this enough: our diet is our primary medicine, and more sensible consumption, with unprocessed products, would also limit exposure to emulsifiers.

In recent years, the idea of using gut microbiota as a diagnostic tool has captured the imagination of the medical community. Yet, despite mounting interest, the clinical benefits of microbiome testing remain largely unproven.

A newly released international consensus report ¹ has now thrown light on this pressing issue. Spearheaded by 69 experts hailing from 18 countries, the initiative set out to build a clear, evidence‐based framework to guide clinicians and laboratories in adopting standardized microbiome testing practices.

The right panel

The panel, comprising clinicians, microbiologists, microbial ecologists, computational biologists, and bioinformaticians, embraced the Delphi method (sidenote: Delphi method A structured process for achieving expert consensus through multiple rounds of anonymous surveys and feedback. ) to forge a set of recommendations. Working in five dedicated groups, the experts tackled general principles, pre-test procedures, microbiome analysis, reporting standards, and clinical relevance. Each statement underwent rigorous scrutiny and was rated on a Likert scale, with an 80% agreement threshold ensuring only robust recommendations made the final cut.

The consensus: what you need to know

The below are four recommendations are a MUST for every clinician interested into using the microbiome in their clinical practice. 

• Ditch Direct-to-Consumer: The consensus strongly discourages patients self-requesting microbiome tests. Testing should ideally be initiated by a physician or licensed healthcare professional with a clear clinical rationale. This highlight concerns over misinterpretation and inappropriate interventions.
• Beyond F/B Ratio: Forget the Firmicutes/Bacteroidetes ratio (sidenote: Firmicutes/Bacteroidetes ratio A once-popular but now-questioned measure comparing two major bacterial phyla in the gut, often linked (incorrectly) to health or disease. ) ; experts advise against its reporting due to insufficient evidence. Similarly, routine dysbiosis indices lack validation. Focus should be on comprehensive taxonomic profiling (sidenote: Taxonomic profiling Analyzing a microbial community by identifying and categorizing its members at various taxonomic levels, such as genus or species. ) using 16S rRNA or whole-metagenome sequencing.
• Clinical Context is King: Reports must include detailed clinical metadata (sidenote: Clinical metadata Essential patient details (e.g., age, diet, medications) that accompany a test sample and help interpret microbiome data in a medical context. ) (age, BMI, diet, medications) to aid interpretation. Comparisons to matched healthy controls are crucial. Surprisingly, testing providers should not offer post-test therapeutic advice; this remains the remit of the referring clinician.
• Quality and Transparency: High-quality, accredited labs using validated software are essential. Detailed reporting of the entire testing protocol, from sample collection to analysis, ensures transparency.

Is the water from your kitchen sink the same as that from your shower or next door? Is it always safe to drink? Apparently not! 

Even water hosts diverse microbial communities. These microbiomes differ significantly and are associated with health risks. But that’s not all: according to a new study ¹ published in Nature, they share antibiotic resistance mechanisms.

Few studies on water quality, straight from the tap

The vast majority of microorganisms present in drinking water usually pose no threat to human health. As an integral part of our exposome, they may even contribute to the balance of our gut microbiota. But drinking water can also contain antimicrobial resistance genes (its “resistome”) and pathogenic microorganisms.

Although the quality of drinking water in distribution networks is closely monitored at municipal level, little is known about the water that arrives at taps inside the home. Certain specific factors (reduced pipe diameter, higher temperatures, nocturnal stagnation, type of water heater, etc.) may influence the bacterial communities present in this water.

To better understand these characteristics, researchers recruited residents from 11 households in St. Louis, Missouri (United States). They were asked to collect water from their kitchen and shower taps for a week so that variations – particularly day-to-day variations – in microbiota and the resistome could be examined.

Major findings to consider

Surprisingly, the results of the analyses indicated that the water in each household has a unique microbial signature differing from other households. Furthermore, the microbiome of kitchen water differs from that of the shower.

The researchers also noted the presence of various pathogenic microorganisms, particularly in shower water. For example, Mycobacterium chelonae, a bacterium responsible for skin infections, was present in 50% of households. 

However, what most caught the researchers’ attention was the presence of antimicrobial resistance genes, whose profile was this time similar from one household to the next. They found 162 of such genes, some of which could confer resistance to aztreonam and meropenem, two major antibiotics used to treat recurring infections.

Infertility, which affects about 15% of couples of reproductive age, seems to be strongly linked to dysbiosis of the vaginal microbiota.

However, few studies have previously looked into the differences in vaginal microbiota between women presenting with primary infertility (inability to become pregnant after trying for 12 months) and secondary infertility (difficulty becoming pregnant again after a first pregnancy).

Hence the recent work ¹ aimed at characterizing the dysbiotic vaginal microbiota and its connection to infertility in 136 Mexican women diagnosed with primary infertility (58 women) or secondary infertility (78).

The effect of age

The analysis of vaginal samples showed that age is the primary factor explaining the type of vaginal flora in women in the study.

However, as the researchers point out, the vaginal microbiota evolves over the course of life, particularly with a reduction in protective Lactobacillus and an increased sensitivity to dysbiosis. Therefore, the researchers advanced the hypothesis (yet to be validated) that evolution of the microbiota could explain difficulties conceiving, naturally or with assistance, and thus the increased prevalence of primary infertility among older women.

Two types of infertility, two types of microbiota

In addition, analysis of the vaginal microbiota showed a lower predominance of lactobacilli in women affected by infertility, compared to the flora of fertile women. 

But above all, it showed differences between women suffering from primary and secondary infertility.

• In women suffering from primary infertility, beneficial Lactobacillus crispatus and Lactobacillus gasseri were dominant, but researchers also noted an elevated proportion of Gardnerella vaginalis and Fannyhessea vaginae, bacteria that are both implicated in vaginosis. The presence of G. vaginalis is also strongly associated with HPV.
• In the case of secondary infertility, the presence of G. vaginalis goes hand in hand with that of the Epstein-Barr virus and even of Haemophilus influenzae. Sexually transmitted bacteria, some of them already associated with infertility, are also present in greater numbers: Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Chlamydia trachomatis.

Two research pathways

These results suggest that the composition of the vaginal microbiota could play a decisive role in infertility, and could open the way to personalized therapies based on changing the vaginal microbiota.

In addition, bacterial and viral co-infections seem to exacerbate dysbiosis and contribute cumulatively to infertility. Hence the interest in studies that include not only bacterial assessments, but also viral and fungal ones, to fully understand the role of the microbiota in infertility.

Infertility, a sensitive subject that affects more than 15% of couples of reproductive age, might (also) have its source in our vaginal microbiota!

This idea, already discussed in relation to in vitro fertilization (IVF) or infertility in general, is reinforced by a study ¹ conducted on 136 Mexican women diagnosed with primary infertility (no pregnancy after 12 months of trying) or secondary infertility (difficulty becoming pregnant again after a first pregnancy).

The researchers scrutinized vaginal samples from these women to better understand what is really happening in their microbiota, and the connection with fertility.

Higher age, fewer lactobacilli

First of all, age is revealed to be a crucial factor. The older a woman is, the higher her risk of primary infertility, while secondary infertility seems to affect younger women more. However, it has long been known that the vaginal microbiota evolves with age. Beneficial vaginal bacteria (the well-known Lactobacillus) progressively lose their hegemony and give way to less favorable bacteria. For the researchers, these changes could partially explain why it becomes more difficult to get pregnant naturally (or with medical assistance) when the decades start to add up.

Two types of infertility, two different types of microbiota

But above all, the researchers showed that the women suffering from primary infertility and those diagnosed with secondary infertility presented with different vaginal microbiota.

• Among women suffering from primary infertility, the beneficial Lactobacillus species, although still in the majority, had lost their dominance in favor of bacteria that our vaginas could do without, such as the duo Gardnerella vaginalis and Fannyhessea vagina, implicated in vaginosis (sidenote: Bacterial vaginosis Bacterial vaginosis (BV) is a type of vaginal inflammation caused by an imbalance of the bacterial species that are normally present in the vagina. ) . But that’s not all: the presence of G. vaginalis seems to be strongly associated with human papillomavirus (HPV) infection. Some serious bad actors!
• Among women suffering from secondary infertility, their flora is also disturbed, but in a different way: G. vaginalis often goes hand in hand with the herpes virus; bacteria responsible for sexually transmitted infections (STIs) are also present.

Hence the importance, for the authors, of having not only pathogenic bacteria in our sights, but also viruses, since they seem to work in concert, with a cumulative impact on infertility. There is still hope, however: the vaginal microbiota should help us better understand infertility and come up with personalized treatments.

It is here, within the labyrinth of the human gut, that the Parkinson’s disease drug entacapone is waging an unintentional war. In a revelation that could reshape our understanding of drug-microbiome interactions, researchers have uncovered entacapone’s unforeseen impact on gut bacterial communities, with consequences that extend far beyond its intended neurological effects.

Entacapone: a master of iron deception

Entacapone has long been heralded as an essential aid for patients battling Parkinson’s disease, extending the effectiveness of levodopa by inhibiting its breakdown. Yet, as this drug journeys through the digestive tract, it performs a remarkable feat of molecular deception. Entacapone binds iron with astonishing efficiency, acting as a chelator that depletes available iron from the gut environment.

Iron, a fundamental nutrient for both humans and microbes, is suddenly rendered scarce. The consequences of this depletion ripple through the microbiome, selectively starving some bacterial populations while allowing others to flourish.

This subtle yet profound shift in microbial balance could help explain why patients respond differently to entacapone therapy. The presence or absence of key bacterial species, many of which play a crucial role in metabolizing medications and regulating immune function, may dictate whether the drug achieves its intended effect or contributes to unwanted side effects.

A hidden risk: entacapone and the rise of resistant microbes

Perhaps the most unexpected and troubling finding from this study is the selection of antibiotic-resistant and virulent bacterial strains. The iron starvation triggered by entacapone appears to favor microbes equipped with genetic adaptations that allow them to survive in these challenging conditions.

Among them are bacteria harboring genes associated with antimicrobial resistance (AMR), raising the possibility that long-term entacapone use could contribute to an increased risk of drug-resistant infections. This revelation is particularly significant given the growing global crisis of antimicrobial resistance.

If entacapone is indirectly fostering an environment in which resistant bacteria thrive, it adds a new layer of complexity to the management of Parkinson’s disease and patient health. Should clinicians screen for microbiome composition before prescribing entacapone? Could concurrent therapies, such as targeted iron supplementation, mitigate these effects? These questions now demand urgent exploration.

Implications for treatment: rethinking parkinson’s care

The intricate dance between drugs and the microbiome is only beginning to be understood, yet this study signals the necessity for a more holistic approach to Parkinson’s treatment.

One promising intervention is the timing of iron supplementation. Because oral iron can reduce the absorption of entacapone, supplementing at a different time of day, or even developing targeted delivery systems to replenish gut iron levels, could restore microbial balance without interfering with medication efficacy.

Additionally, precision medicine approaches could refine entacapone therapy by factoring in a patient’s unique microbiome composition. If certain microbial profiles predict a higher risk of dysbiosis, clinicians might adjust drug dosages or consider alternative treatments.

Every day, millions of people take medications to treat illnesses, believing these drugs work only on the condition they’re meant for. But what if a pill taken for Parkinson’s disease was also changing the delicate balance of bacteria in your gut? New research has uncovered a surprising link between entacapone, a common Parkinson’s drug, and changes in the gut microbiome - the community of bacteria living in our intestines.

A medication that does more than expected

Entacapone is often prescribed to help Parkinson’s patients by making their primary medication, levodopa, work longer. But scientists have found that it does something else: it binds to iron in the gut, preventing bacteria from accessing this essential nutrient. This shifts the natural balance of the microbiome, encouraging the growth of certain bacteria, particularly Escherichia coli (E. coli).

You may have heard of E. coli in the context of food poisoning, but in reality, many types of E. coli live harmlessly in the intestines. However, when their numbers grow too much, they can cause digestive problems and may even be linked to long-term health issues. The study suggests that people taking entacapone might experience unintended effects on their gut health, as the bacterial community is disrupted by the drug’s impact on iron availability.

Why does this matter?

The gut microbiome isn’t just responsible for digestion, it plays a role in metabolizing medications. Some gut bacteria can break down drugs before they even reach the bloodstream, while others can alter how effective a treatment is. Since entacapone affects which bacteria thrive and which struggle, its effectiveness may not be the same for every patient.

This means two people taking the same dose of entacapone could respond differently to the drug. One might see excellent results, while another could have a less effective treatment because their gut bacteria are interfering. Understanding these interactions is key to improving future treatments, ensuring that medications work as intended without disrupting gut health.

Looking to the future

So what can be done? Scientists suggest that finding ways to balance the microbiome could help Parkinson’s patients avoid these potential problems. One idea is adjusting iron levels in the gut, perhaps through supplements taken separately from entacapone, to prevent excessive changes in bacteria like E. coli.

For now, healthcare professionals are encouraged to consider the gut microbiome when prescribing entacapone. More research is needed to fully understand how to prevent these changes, but this study opens the door to a more personalized approach to medication, where doctors could tailor treatments based on an individual’s gut bacteria.

The microbiome is a vast and complex world within us, and as we learn more about its role, we may discover that taking care of our gut health is just as important as treating the disease itself.

While the close link between bacteria in the ENT microbiota and chronic respiratory diseases is now well documented, little is known about the role fungi play in these disorders. Studies have shown that fungal communities play a role in asthma, but few have looked specifically at the fungi present in the nasal cavities. 

Researchers at the University of Porto in Portugal ¹ decided to take a closer look by comparing the nasal mycobiota of people suffering from allergic rhinitis and/or asthma with that of healthy people. To do so, they took nasal samples from 339 Portuguese children and young adults divided into four groups based on their health status:

• allergic rhinitis (47 people)
• allergic rhinitis and asthma (155 people)
• asthma (12 people)
• no respiratory disease – control group (125 people)

Significant difference in fungal environment

The scientists then determined the taxonomic composition, interactions, functional diversity, and metabolic pathways of the fungi using next-generation sequencing techniques.

In all participants, they found 14 different genera of fungi belonging to two families, Ascomycota and Basidiomycota. Among these genera, fungi such as Aspergillus, Candida, and Penicillium, known to be allergens or opportunistic pathogens, were identified. According to the researchers, this proves that the nasal passages are a major reservoir of agents capable of causing allergic rhinitis or asthma.

They also found that the nasal mycobiota of participants suffering from respiratory diseases differed significantly from that of the control group, presenting richer and more diversified fungal communities. Differences between the various patient groups were, on the other hand, minimal. 

Furthermore, the fungal interaction networks were also more complex and connected in the patient groups, particularly in the case of a combination of rhinitis and asthma, which suggests an influence of fungi on the immune environment of the nose.

Therapeutic targets in sight

One interesting finding was that in the mycobiota of people suffering from both asthma and rhinitis, three metabolic pathways were particularly abundant. They relate to the production of 5-aminoimidazole ribonucleotide (AIR), an intermediate for purine biosynthesis involved in energy metabolism and DNA synthesis. The researchers believe AIR may be a future therapeutic target for the diagnosis and treatment of allergic respiratory diseases. 

But before considering new therapies, further research aimed at gaining a better understanding of the role played by fungi in respiratory inflammation is required. This should involve longitudinal studies that include several samples over time and better consideration of variables specific to patients, e.g. severity of the disease, treatments, etc. 

Itchy and runny nose, sneezing, and conjunctivitis in the case of allergic rhinitis. Shortness of breath, wheezing, coughing, and chest tightness in the case of asthma.

Are these typical symptoms of chronic respiratory diseases familiar to you? If so, it might interest you to know that the populations of microscopic fungi in the nose (i.e. mycobiota) of healthy people are probably very different from those in the nose of chronic respiratory disease patients. This difference could be very good news for the diagnosis of such conditions and for the development of new treatments.

Delving into the mysterious world of nasal fungi

It has long been known that dysbiosis of the microbiota, in particular the ear, nose, and throat (ENT) microbiota, plays a role in the onset and progression of respiratory diseases such as allergic rhinitis (hay fever) and asthma. Numerous studies have looked at the bacterial component of the ENT microbiota. But what about its fungal component?

To answer this question, a team led by immunologist Dr Luis Delgado at the University of Porto in Portugal recruited 339 children and young adults, 125 of whom were in good health and 214 suffered from either rhinitis, asthma, or both conditions. The scientists then took nasal microbiota samples from all participants to specifically analyze the nature and organization of the fungal communities.

Firstly, they found the mycobiota of participants suffering from respiratory diseases to be very different (considerably richer and more diversified) from that of healthy people.

Among the genera common to all participants, sick or otherwise, the researchers found certain fungi known to be opportunistic pathogens, such as Aspergillus and Candida, among others. For the researchers, this may be evidence that the nasal cavities act as a reservoir of potentially harmful fungi that promote rhinitis and asthma, similar to what we know about bacteria.

Potential treatment options

In those suffering from both rhinitis and asthma, and therefore particularly affected by inflammation, it appeared that the fungal networks were more interconnected than in those suffering from rhinitis only or those who had no health problems. This indicates that fungi are very likely to be sensitive to the immune environment.

While this work has enabled Dr Delgado’s team to identify potential targets for future diagnostic or treatment tools, a crucial question remains: is the presence of a specific fungal population the result of inflammation of the nasal mucosa or the cause of this inflammation? Longer-term studies that place greater emphasis on patient profiles will be needed to answer this question. This initial study is nonetheless a big step in the right direction.