Founded in France in 2021 by the ENDOmind Association under the aegis of the Foundation for Medical Research, the Foundation for Endometriosis Research aims to accelerate research on a disease that affects one in 10 women: endometriosis. Each year, the Foundation funds research projects aimed at understanding the pathology of endometriosis, improving diagnosis and developing more effective treatments.

In 2024, the Foundation for Endometriosis Research Executive Committee decided to more clearly define its research priorities for endometriosis and maximise its research impact. To this aim, the Foundation coconstructed and co-funded an innovative collaboration with the Curie Institute in Paris, seeking to compare the cellular microenvironments of endometriosis lesions and ovarian cancer. This ambitious project is starting in 2025 and illustrates the Foundation’s desire to encourage cross-disciplinary and innovative research
approaches.

Furthermore, the Foundation for Endometriosis Research has initiated a multidisciplinary scientific investigation with European experts on the links between microbiota and endometriosis. The Foundation will call for expressions of interest later in 2025, with the objective of launching new research work at the start of 2026, with financial support.

By focusing its efforts on strategic themes, the Foundation for Endometriosis Research confirms its role in accelerating research and ultimately contributing to improving the quality of life for the millions of women affected by this still little-known disease.

Key achievements of the Foundation for Endometriosis Research:

What is the prevalence of endometriosis?

A.H.: Endometriosis is surprisingly common – as common as asthma and diabetes. It affects an estimated 1 in 10 women.

W.F.: In my practice of irritable bowel syndrome (IBS), it’s even more common – certainly more than 25%.

What are the signs and questions to ask to avoid missing a diagnosis?

A.H.: Signs are varied and diagnosis can be difficult. The main symptom is chronic pelvic pain, which can often be debilitating, disrupting life and work. But, patients can also present with painful sex, chronic fatigue, diarrhoea and/or constipation and urinary symptoms. Any cyclical symptom can be a red flag for endometriosis.

W.F.: Increased peristalsis and softer stools during menstruation are normal, but significant and cyclical diarrhoea may not be so. Pain is expected, but not to the point of being bedridden.

A.H.: Another symptom that causes alarm is infertility. But I reassure patients with endometriosis: two-thirds of them won’t have trouble getting pregnant, and those who do generally respond well to surgery or IVF.

W.F.: I would add that endometriosis is chronic, but that doesn’t mean it’s untreatable. It’s important that any specialist involved with the care of these patients reinforces that message.

How common are digestive symptoms in women with endometriosis?

A.H.: The true prevalence isn’t known, but nearly all my patients have digestive symptoms – bloating, bowel changes, heartburn. Lesions on the bowel wall explain some symptoms, but many have superficial peritoneal disease, making the link harder to define.

W.F.: I have observed similarly, and would state that inflammatory bowel disease (IBD) is four times more common in women with endometriosis compared with the general population (4% vs 1%). IBD and endometriosis are both autoimmune conditions; having one increases the risk of the other.

Is there a need for multidisciplinary management?

A.H.: Endometriosis is a systemic inflammatory disorder. As gynaecologists, we’re not equipped to manage digestive symptoms. In Edinburgh, I’ve recently set up a joint gynaecology–gastroenterology clinic.

W.F.: When the abdominal pain strictly relates to menstruation, the gastroenterologist may find it difficult to add much. When the relationship is more loosely defined, we should investigate. Persistent digestive symptoms despite treatment may signal coexisting IBS. Also, be mindful of medications, particularly nonsteroidal anti-inflammatory drugs (NSAIDs). Occasional use is fine in young patients, but chronic use may require a proton pump inhibitor (PPI), which can cause dysbiosis. There’s no universal rule — we must tailor care to each patient.

Are gut and vaginal microbiota involved?

A.H.: There’s growing interest in the role of the gut and vaginal microbiomes in endometriosis. Some studies suggest associations, but they’re small and flawed. We need large cohort studies. I believe the microbiome plays a role, but it’s still unclear as to which comes first — microbiome changes or endometriosis. If microbiota drive symptoms, this could open the path to new treatments.

W.F.: It’s an exciting field. In patients with endometriosis, we observe gut dysbiosis with reduced short-chain fatty acids like acetate, propionate and butyrate that protect gut permeability. The same pattern can be seen in other gastroenterological conditions, like IBS or IBD, but we don’t yet understand the relationship. Maybe one day, we’ll personalise care by restoring exact missing strains. For now, we don’t know what causes what, so mechanistic studies are needed.

Should we recommend specific diets to patients with endometriosis?

W.F.: There’s no universal diet for endometriosis and we shouldn’t offer false hope. Allergies, lactose intolerance, and coeliac disease might be involved. The best step is to refer patients to a nutritionist.

A.H.: No specific “endometriosis diet” exists, but many patients report symptom relief after dietary changes. In my clinic, patients work with a dietitian to carefully adjust their diets. In our international survey of 2,500 patients with endometriosis, some found relief by stopping consumption of alcohol and caffeine, or foods containing gluten. However, without guidance, dietary restriction can be harmful.

Historical perspective

The beginning of the long journey towards the understanding of the vaginal microbiome can be attributed to Albert Döderlein, at the end of the 19th century. In his book Das Scheidensekret und seine Bedeutung für das Puerperalfieberhe pointed out that “normal”, healthy women have the vagina dominated by Grampositive bacilli, which he named Lactobacillus acidophilus.

This concept still shapes contemporary interpretations of the vaginal microbiome, but the reality is probably far more complex.

Understanding of vaginitis is still incomplete, and its management mostly empirical, despite being one of the most common causes for  women to seek a medical appointment¹.

In 2011, Ravel et al. published one of the most important and mind-changing papers in terms of understanding of the human vaginal  microbiome. In that paper they demonstrated that asymptomatic is not synonymous with “normal” (leading also to the question of what 
is a “normal” – or, probably more accurate, “optimal” – vaginal microbiome) and that there are striking differences according to ethnicity².

Diversity is the rule in nature, but the human vagina seems to be an exception: the accepted “optimal” vaginal microbiome is dominated by one or two species of lactobacilli (low alpha diversity). If we think about other organs or anatomical regions, dominance by one species 
is usually synonymous with disease (infection). If we perform the same exercise considering any ecological system, it represents the last 
step before collapse (e.g. monocultures of plants never occur in nature, and when performed artificially they must be limited in time). We can look for further explanations for this apparent “abnormality” (or “exception”) in nature, but it does seem to lead to a dead end. 

Should we, instead, change the focus of our lens and investigate gene pools rather than species or genera to overcome this apparent 
biological abnormality

The ultimate goal of living beings seems to be passing genes to the next generations and evolution seems to be much driven by this 
primordial “instinct”. Therefore, we can easily assume that the human vaginal microbiome should be a fulcral part of the end-product 
of evolution to optimise the reproductive process. If this premise is correct, we can expect

1. evolutionary congruence (as has been shown, for instance, in the gut);
2. any differences should be more or less easily explained (mating process, diet, geographical location, etc.) and, naturally
3. higher similarity in closely related species.

Surprisingly, none of the three premises are satisfied. In nature, phylogeny cannot be related with the vaginal pH (a very indirect marker of the vaginal microbiome composition), and dominance by lactobacilli is unique to the human species. Even when comparing humans with other primates, the differences are huge and, currently, not easily explainable^3,4. What made the human vagina so unique? Was it the fruit of random events or the evolutionary corollary of the continuous ovarian cycle, high risk of lacerations and infection at birth, or agriculture and the consequent high consumption of starch³?

The microbiome and pregnancy

One issue seems to be beyond doubt: lactobacilli are fundamental for the success of pregnancy – but it is not so clear if the same 
applies to achieving a pregnancy⁵.

The available data clearly show that a vagina not dominated by lactobacilli during pregnancy is associated with negative obstetrical and puerperal outcomes, including preterm labour, premature rupture of membranes, and puerperal infections (Figure 1). Of note, one million babies die every year from prematurity-related complications⁶.

We are used to repeating that lactobacilli have a protective role and that their presence is desirable, but to assume that means we must ignore some obvious facts, such as that this dominance does not occur in children, during breastfeeding, nor in postmenopausal women. Therefore, we can theorise that our symbiotic relation with lactobacilli serves us a purpose during the reproductive years. We can consider that this purpose includes a reduction in the risk of sexually transmitted infection (STIs) (which pose a risk to the success of reproduction and to the offspring), of ascending genital infections (and consequent abortion, stillbirth, and preterm birth), as well as of puerperal complications. The role of the microbiome in achieving pregnancy seems to be more limited. For instance, populations with high rates of vaginal dysbiosis do not seem to be less fertile⁷

Figure 1. Vaginal lactobacilli dominance is associated with beneficial obstetrical and puerperal outcomes

In the same way, the impact of the cervicovaginal microbiome on the outcome of fertility treatments is also unclear⁵.

One of the biggest evolutionary differences between humans and other mammals has to do with delivery – the difficult balance between being born with a large cephalic perimeter and negotiating it with a pelvis that had to adapt to bipedalism. Humans have the most difficult deliveries – perhaps surpassed only by hyenas. Can this hold the key to understanding the uniqueness of the human vaginal microbiome? Whatever the evolutionary purpose was, for most women of reproductive age, even out of pregnancy, the dominance of lactobacilli in the vagina is the desirable state. But lacking lactobacilli, despite representing a dysbiotic state, is not synonymous with disease.

Our understanding of the role of the vaginal microbiota is still very limited. Even apparently simple questions, such as how lactobacilli
colonise the vagina still does not have a clear answer.

The vulvovaginal microbiome in heath and disease

The most noticeable effect of an altered microbiome is vaginitis. Most women will suffer at least one episode of candidiasis and, in some populations, more than half of reproductive-aged women have bacterial vaginosis (BV), asymptomatic most of the time (figure 2A and 2B). We have a limited understanding of what drives these shifts (“normal” – colonisation/asymptomatic state – symptomatic)⁸.

Figure 2. Microphotographs of wet mount microscopy preparations (phase contrast 400x)

(A) Normal lactobacilli, presence of Candida spp. blastospores (circle); (B) Bacterial vaginosis
(absence of lactobacilli and overgrowth of anaerobic and facultative bacteria).

However, the bacterial profile of the vagina,regardless of symptoms, may confer differentprofiles of risk or protection. In general, it is considered that Lactobacillus spp. tendto confer health benefits. However, not all species are equal and only a limited number of the existing species are usually found in dominating states in the vagina. L. iners, with a significantly smaller genome and different metabolic profile, is usually associated with dysbiotic or transition states⁹.

Table 1. Gynaecological and obstetrical conditions and their associations with the vulvovaginal microbiome.

While there are no current recommendations to treat asymptomatic dysbiosis (e.g. BV), it has been associated with obstetrical and non-obstetrical complications (including risk of acquiring STIs [HPV, HIV])⁸ (Table 1).

Once efficacious (preferably non-antibiotic) strategies are available, it may be advisable to screen and treat dysbiosis in women at increased risk of STIs or even in those infected with HPV. This, however, may prove more complex than it appears. The STI-like behaviour of BV has long been acknowledged, but recent data have confirmed it, as well as suggesting that reduction of recurrences may require treatment of partners, which may represent a great obstacle to prevention strategies¹⁰.

BV is a common syndrome, in which there is depletion of lactobacilli and an overgrowth of several strictly and facultative anaerobic bacteria, associated with formation of a biofilm that seems to contribute to the frequent relapses after treatment. The composition of BV is variable from woman to woman – and probably even in the same woman over time¹¹. Currently it is possible to diagnose BV using molecular tests, but it is expected that with the increasing knowledge of the vaginal microbiome, these tests will allow for the “profiling” of BV, the evaluation of the resistome, and a more rationale choice of treatments⁸.

The relationship between Candida spp. and the vaginal microbiome is very complex and far from fully understood. While candidiasis can exist with any vaginal microbiome, it tends to be more common with lactobacilli dominance (and the consequent low pH)¹².

Several gynaecological conditions have been associated with specific microbiome characteristics and, almost systematically, a reduction in lactobacilli confers an increased risk for STIs and gynaecological cancers (even of the upper genital tract). However, a causal relationship between the microbiome deviations and the specific conditions is not always straightforward. We can, however, expect to one day assess or modulate the risk of cancer through the evaluation of the vaginal microbiome – especially for cervical cancer¹³.

The interest and knowledge in the vulvar microbiome is more recent and the amount of data is scarce, but its role in entities such as vulvodynia, vulvar dermatoses, vulvar intraepithelial neoplasia and cancer is being studied^14-16.

What’s next?

Giant strides are being made towards the understanding of the vulvovaginal microbiome. Until we fully understand the microbiome, we can start by respecting it and its functional role, recognising that each woman is unique (and that this uniqueness is mutable), avoiding
unnecessary use of antibiotics and antiseptics, and properly diagnosing STIs and vaginitis, rather than relying on empiricism. Accurate diagnosis will minimise wrong treatments, with a potential long-term impact.

At this stage, it is essential to distinguish what is investigational and what is clinically relevant. We are in a process of learning and attempting to use investigational techniques and concepts in clinical practice that often leads to unnecessary testing, expenses, and
treatments – for instance, metagenomics is a very useful research tool, but it currently has no place in the clinical evaluation of vaginitis.

In the last two decades we have amassed a huge quantity of information, which will soon translate into better health care for women, including specific dietary recommendations, and pre- and probiotics. We can expect that this knowledge will substantially reduce preterm labour, gynaecological cancers, as well as the recurrence of vaginitis and cystitis.

The next chapters will undoubtedly be the most exciting ones!

A woman’s vaginal microbiota undergoes changes over the course of her life, sometimes to the point of shifting type, as shown by a study ¹ including 125 sexually active women aged 18 to 25 in the south of France (Montpellier).

Lactobacilli, guarantors of stability

The study’s first finding was that bacterial communities dominated by lactobacilli — rod-shaped bacteria known to be most beneficial to women’s intimate health — are more stable over time. In other words, vaginal microbiota rich in lactobacilli such as L. crispatus, L. gasseri, L. jensenii, or L. iners are more difficult to disrupt.

A balanced vaginal microbiota dominated by these lactobacilli will limit the proliferation of pathogens, but if too much stress is put on the microbiota, pathogens can proliferate anyway.

Drinking parties, disrupted vaginal flora

The second finding was the list of factors that can wreak havoc on our vaginal flora.

In the 125 students studied, alcohol was identified as the factor with the strongest and most consistent effect, promoting suboptimal flora and increasing vagina’s vulnerability to infections, particularly by facilitating proliferation of pathogenic bacteria.

Partners, hygiene, and antibiotics

Other factors may also influence the transition from one vaginal bacterial community to another:

• A higher number of sexual partners may increase the risk of maintaining (or switching to) non-optimal flora, thereby promoting the development of vaginal infections that can progress to bacterial vaginosis. 
   

• The effects of intimate hygiene products (creams, tablets, capsules, gels, and wipes) on women’s health appear to vary from one woman to the next, with possible circular changes from one type of flora to another. 

• As for antibiotic use — whether local treatments for bacterial vaginosis (genital application of metronidazole) or systemic treatments (oral antibiotics) — it appeared to be only loosely associated with transition to a different type of vaginal flora. This absence of an effect surprised the researchers: were the samples taken too far apart to “capture” any short-lived change in flora linked to antibiotics?

In zebrafish (Danio rerio), a bacterial protein promotes the proliferation of β cells in the islets of Langerhans. But what about mammals? Β-cells are necessary for sufficient insulin production, and their proliferation increases rapidly after birth, at the same time as the gut microbiota diversifies.

Is this a mere coincidence or is there a genuine correlation, as in zebrafish? A British team ¹ has settled the question by showing in mouse pups that postnatal β-cell development is stimulated by bacterial and fungal species during short colonization windows, periods also critical for metabolic health.

In mice and humans

By eliminating and restoring microbiota at different pre- and postnatal periods in mouse pups, the team identified a critical period (from 10 to 20 days after birth) during which the gastrointestinal flora is essential for the establishment of a normal mass of β cells. These observations were confirmed by experiments with antibiotics and antifungals, highlighting the involvement of bacteria and fungi in maintaining glycemic balance.

And in humans? Fecal samples from human infants aged 7 to 12 months (but not from other age groups) strongly stimulated β-cell mass in mice. Humans therefore also appear to have a window of colonization by microorganisms that promote β-cells.

This is yet another argument in support of the much-publicized 1,000-day window of opportunity for future health and the prevention of metabolic diseases such as obesity.

Bacteria and fungi responsible

The comparison of microbial communities capable of inducing (or not) β-cell development has identified bacterial and fungal taxa involved in the case of mice: Escherichia coli, Enterococcus gallinarum, and Candida dubliniensis. The latter proved to be the most effective, thanks to a mechanism involving macrophages and β-cells, which allows the recognition of specific signals from the cell wall of commensal yeasts.

Lastly, not only does C. dubliniensis reduce the prevalence and severity of diabetes in mouse models, but it also helps restore the β-cell population after ablation or underdevelopment following antibiotic treatment. By disrupting gut microbiota during early childhood, these treatments can alter glycemic regulation and interfere with the maintenance of stable body weight. Could C. dubliniensis be used prophylactically to make up for losses induced by antibiotic treatment, particularly in individuals predisposed to type 1 or type 2 diabetes or obesity?

Preventing or even reversing β cell loss?

This study shows that there may be a critical window in young children, between 7 and 12 months, during which certain bacteria and fungi are necessary for the development of β-cells in the pancreas. If this developmental window is missed, β-cell development may be compromised, leading to dysfunction and an increased risk of metabolic diseases such as obesity and diabetes.

However, the mechanisms identified by the authors of the study have the potential to prevent or even reverse the loss of β-cells, provided intervention comes early and takes into account the key role of the gut microbiota.

According to a new study, in women scheduled for endometrial polyp removal, a vaginal microbiota is well balanced before removing uterine polyps? According to a study published in the European Journal of Obstetrics and Gynecology, this may be the case. The authors, researchers at Nanning University in China, demonstrated that the presence of a vaginal dysbiosis was a major risk factor for the recurrence of polyps after surgical removal. ¹

The link between dysbiosis and recurrence results from the impact of this microbial imbalance on the vagina and uterus, two anatomical areas closely connected in terms of immunity and microecology.

Nearly 700 women enrolled

To obtain this result, the researchers collected vaginal secretion samples from 679 women aged 25 to 50 who were undergoing “hysteroscopic resection,” a procedure to remove endometrial polyps. 

After the procedure, the women were followed for two years and the researchers identified a recurrence of polyps in 105 of them.

An analysis of the secretions indicated that women who had vaginal dysbiosis before the operation were 3.3 times more likely to experience a recurrence. This was also the case for women with endometriosis.

An analysis of the microbiotes vaginauxindicated that, in women who suffered from recurrence, the density and diversity of bacteria, as well as the presence of Lactobacilli, were significantly lower than in those with no recurrence. There were also more pathogenic microorganisms, such as the bacterium Gardnerella vaginalis and the fungus Candida, which cause vaginosis and yeast infections, respectively.

The researchers also observed increased activity of certain enzymes, such as leukocyte esterase, a sign of persistent inflammation in the vagina, which can promote infection spreading upward to the uterus.

Decline in Lactobacillus, a key factor in recurrence

How are these abnormalities in the vaginal microbiota involved in the recurrence of polyps? The researchers believe the answer lies with Lactobacillus.

Under normal circumstances, these bacteria produce bacteriocins, substances capable of destroying pathogens, as well as lactic acid, which acidifies the vaginal environment and stabilizes microbiota. They also synthesize molecules called glycerophospholipids, which in turn promote secretion by the body of anti-inflammatory messengers called prostaglandins. Lastly, they increase the synthesis of proteins that are involved in the integrity of the vaginal wall.

Thus, by reducing the risk of infection and inflammation after surgery, Lactobacillus may help protect against polyp recurrence.

This beneficial action is all the more important in women with a history of chronic microbial imbalances or endometriosis, for whom the risk of recurrence is significantly higher.

Towards preventive treatments

The researchers highlight the importance of maintaining the balance of the vaginal microbiota, particularly the long-term dominance of Lactobacillus, in cases of uterine polyps. They suggest several possible preventive treatments:

• a combination of probiotiques and antimicrobials, which would make it possible to tackle immediate pathogenic imbalances while promoting long-term microbial health;
• lactic acid-based gels or vaginal suppositories;
• bacteriophages, viruses capable of selectively destroying pathogenic bacteria without disrupting the microbiota;
• prebiotics and omega-3 fatty acids, which promote balanced microbiota.

These modulation strategies could also improve overall vaginal health by reducing the risk of persistent infection.

While studies are still needed to evaluate the effectiveness of these interventions, these avenues are promising. Keep informed!

The abscopal (sidenote: Abscopal effect From Latin ab-, “away from”, and Greek skopos, “target,” lit. “away from target” - Regression of tumor lesions located outside the field of irradiation when irradiation of a lesion activates antitumor immune responses or enhances their effectiveness, thereby leading to the destruction of non-irradiated lesions by antitumor immune effectors. Explore https://doi.org/10.1016/j.mednuc.2024.11.007 ) effects of radiotherapy are one of the mysteries of cancer research, observed in some patients but not in others. However, in 2025, an international team made a major breakthrough, showing that intestinal low-dose irradiation (ILDR) increased the clinical benefits of chemotherapy and immunotherapies that target checkpoint inhibitors (sidenote: Immune checkpoints are used by tumors to protect themselves from immune system attacks and may be blocked by ICI therapy in order to restore the immune system function. ) , in eight retrospective patient cohorts and a preclinical murine model. This research highlights the key role of the gut environment in treatment response.

A matter of dose...

The researchers’ starting point was patients with metastatic tumors in a phase 2 multicenter trial who received stereotactic ablative radiotherapy (SABR) (sidenote: Stereotactic ablation radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT) Is radiotherapy based on the emission of numerous radiation beams from different angles that converge on the tumor. The tumor therefore receives a high dose of radiation, while beams that pass through the surrounding tissue are low-dose. This reduces the effects of radiation on the healthy tissue surrounding the tumor. SBRT is administered in fewer sessions than standard external radiation therapy. SBRT can be used to treat tumors in the pancreas, lungs, liver, or spine. Explore https://cancer.ca/fr/treatments/treatment-types/radiation-therapy/external-radi… ) in combination with an anti-PD-L1 antibody. Among them, 13 patients (41%) exposed to accidental ILDR, with a median radiotherapy dose of 3.3 Gy to the duodenum, 1.0 Gy to the jejunum/ileum, and 1.3 Gy to the colon, showed a much better 24-month survival rate of 38% (5/13) versus 5% (1/19). This highlights the increased efficacy of combination therapy.

Treatment with ILDR at 1 Gy alone did not improve survival, while anti-PD-L1 alone had only transient effects (relapse). However, combining ILDR at 1 Gy with anti-PD-L1 cured 30% of animals, unlike lower (0.25 Gy) or higher (4 Gy) doses, which did not cure any mice. This shows that the effectiveness of treatment depends on a precise synergy between radiation dose, immunotherapy, and immune cells.

... and bacteria

The anti-tumor immune response and survival also appear to be linked to differences in gut flora between individuals: compared to healthy adults, non-responders to treatment combining ILDR and anti-PD-L1 antibodies harbored – prior to treatment – fewer species of bacteria typical of responders (Christensenella minuta and Ruminococcus bromii) and more species of bacteria typical of a poor response to treatment (Enterocloster aldensis and Parabacteroides distasonis).

It appears that metabolic and immune interactions between the host and the gut microbiota allow CD8⁺ T cell activation. Various strains of Christensenella minuta appear to selectively boost the efficacy of ILDR and anti-PD-L1 by allowing migration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes.

For years, dentists and researchers have focused on the “bad” bacteria in our mouths, like Porphyromonas gingivalis, as the main culprits behind gum disease. But this new study from Kyushu University, Japan, reveals that the real damage may come not just from the bacteria themselves, but from the chemicals they produce. ¹

These chemicals, called metabolites, are small byproducts that microbes release as they feed and grow. Think of them as chemical footprints. And some of these footprints are toxic. Researchers found that when these metabolites build up, they can irritate and even damage the cells that line our gums, triggering inflammation that contributes to periodontal disease.

Beyond bacteria: it’s what they do that matters

To uncover these links, the researchers collected mouth-rinsed water samples from two groups: 24 people with gum disease and 22 healthy individuals. This type of sample provides a snapshot of the oral microbiome and its activity, similar to a “saliva fingerprint.”

They used advanced tools to identify not only which bacteria were more common in the disease group, but also what metabolites were present. Next, they took 20 of these metabolites and tested them directly on human gum cells in the lab.

The gingival epithelial cells (sidenote: Gingival epithelial cells These are the surface cells that form the lining of the gums and act as the first barrier against microbial invasion in the oral cavity. )  are the host’s first line of defense in the subgingival space where dental plaque accumulates, they are used to replicate what’s happening in the mouth.

This step allowed them to see not just associations, but real biological effects, giving strong clues about which compounds might be fueling gum damage.

The scientists found that several of the disease-linked metabolites, especially homoserine (sidenote: Homoserine An amino acid derivative not commonly found in human metabolism but produced by certain bacteria; it may have pro-inflammatory or cytotoxic effects on host tissues like gum epithelium. ) , propionate, succinate, and citrulline, were shown to impair host cell growth and promote inflammation, central to the development of periodontitis. These substances didn’t just sit there; they actively slowed down cell growth and triggered the release of IL-8 (sidenote: Interleukin-8 (IL-8) A signaling protein (cytokine) released by cells to attract immune cells like neutrophils to the site of infection or inflammation; elevated IL-8 often indicates ongoing tissue inflammation. ) , a key molecule in the body’s inflammatory response.

Even more unexpected? Homoserine, a compound not previously associated with oral disease, was being produced by some of the worst bacterial offenders, including Prevotella intermedia and P. gingivalis. That means these microbes aren’t just “bad guys” by association; they may be actively producing the toxins that make gum disease worse. Moreover, the presence of these bacterial metabolites is consistent with dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) of the subgingival microbiota, where an imbalance in dental plaque promotes disease onset.

So what does all this mean for you and your dentist?

This insight shifts the attention toward how specific species contribute to oral inflammation, not just through colonization but through metabolite activity in the subgingival dental environment. For a long time, the focus in treating gum disease has been pretty straightforward: find the bad bacteria and get rid of them. That’s why treatments often involve deep cleanings, antiseptic rinses, or antibiotics, to wipe out the germs.

But this study is telling us that the real issue might not just be which bacteria are in your mouth, but what those bacteria are doing.

These microbes are like tiny chemical factories. Some of them pump out substances that irritate and inflame your gums, even if the bacteria themselves aren’t in huge numbers. That’s a big deal. It means that just killing bacteria might not be enough; we may need to target the harmful substances they produce instead.

In the near future, your dentist might not just check for plaque; they might test your saliva for these damaging chemicals and tailor your treatment based on what your oral microbiome is up to. It’s a whole new frontier in personalized, microbiome-based dental care.

Why saliva and subgingival samples matter

Although mouth-rinsed water was used in this study, researchers noted that subgingival plaque samples provide an even more accurate reflection of the microbiota at lesion sites, especially in cases of periodontitis. Combining microbial and metabolite analysis from subgingival plaque could soon become a gold standard in oral health diagnostics.

Periodontal diseases (gum diseases) represent a major global health concern. A significant contributing factor to their development and progression is dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) of the oral microbiota. Historically, we've focused heavily on identifying pathogenic species of bacteria, but this new study ¹ shines a spotlight on another critical layer: the metabolites these microbes produce, and how they directly influence the health of our gum tissues.

The study shows that the imbalance in the oral microbiota directly affects the quantity and compositional balance of metabolites. Some metabolites correlated with bacteria prevalent in periodontitis can exhibit inflammation-inducing effects on human gingival epithelial cells (sidenote: Gingival epithelial cells These are the surface cells that form the lining of the gums and act as the first barrier against microbial invasion in the oral cavity. ) . This demonstrates a clear link between the altered oral microbial ecosystem, its metabolic output, and the inflammatory response in the host tissues.

Microbiome-metabolite connection

The authors, from Kyushu University Faculty of Dental Science, Japan, examined mouth-rinsed water from individuals with periodontal disease (n=24) and healthy controls (n=22). Mouth-rinsed water is considered an appropriate sample as it reflects information present in saliva. They didn't just identify the bacteria more prevalent in disease states, confirming the usual suspects like Porphyromonas gingivalis and Fusobacterium nucleatum, but crucially, they correlated these specific bacterial species with the metabolites found in the same samples. This targeted approach identified 20 metabolites strongly associated with the periodontitis microbiome. These weren't just random compounds; they included things like amino acid derivatives, 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. ) , and polyamines.

Metabolites with pathogenic effects

The next critical step was to see if these identified metabolites could actually do something to human gum cells. They tested 20 correlated metabolites on human gingival epithelial cells. The results showed that several compounds exhibited clear signs of pathogenicity. Specifically, propionate, succinate, homoserine (sidenote: Homoserine An amino acid derivative not commonly found in human metabolism but produced by certain bacteria; it may have pro-inflammatory or cytotoxic effects on host tissues like gum epithelium. ) , and citrulline significantly inhibited the growth of these gum epithelial cells. Furthermore, treating cells with homoserine, propionate, and succinate significantly ramped up the expression of IL-8 (sidenote: Interleukin-8 (IL-8) A signaling protein (cytokine) released by cells to attract immune cells like neutrophils to the site of infection or inflammation; elevated IL-8 often indicates ongoing tissue inflammation. ) , a key inflammatory cytokine, indicating these metabolites can trigger local inflammation and contribute to plaque-induced tissue damage. 

Finally, while homoserine was known to be produced by other bacteria, this study presented a new finding by detecting its production by several key periodontal bacteria species, including Prevotella melaninogenica, Prevotella intermedia, and Porphyromonas gingivalis. This suggests these periodontitis-associated microbes are directly contributing to the local homoserine levels observed in diseased states confirming their host-impacting potential. 

Solutions for gum diseases?

New dental microbiome-based therapies are offering promising alternatives for treating gum disease by restoring a healthy balance of microbial communities in the mouth. Probiotics, beneficial bacteria found in supplements, have been shown to reduce inflammation and harmful microbes when used alongside traditional dental care.

Other innovative and emerging approaches, such as oral microbiome transplants ² and targeted antimicrobial peptides, are being explored in research settings, with the goal of providing gentler, more effective treatments that address the root cause of gum disease rather than simply eliminating all bacteria.

Microbiota is made up of trillions of microorganisms such as bacteria, viruses, fungi, archaea, etc. It lives in our digestive tract, our skin, our mouth, our nose and our lungs. These organisms play a crucial role in our wellbeing by helping digestion, stimulating our immune system, and protecting us from infectious diseases. But beyond these functions, microbiota also influences our mood, our metabolism and even our longevity. An imbalance of microbiota, often caused by factors such as diet, lifestyle or medication, could lead to major health problems, from digestive disorders to cardiovascular problems and depression. Maintaining a healthy microbiota throughout our bodies is therefore essentialfor our general health and well-being.

This large survey was conducted by Ipsos among 7,500 people in 11 countries (the USA, Brazil, Mexico, France, Germany, Italy, Portugal, Poland, Finland, China and Vietnam). Within each country, a representative sample of the population aged 18 y.o. and over was interviewed. Representativeness was ensured by the quota method applied to the respondent’s gender, age, region and occupation. The survey was conducted online, from January 21 to February 28, 2025.

The results were presented on June 27, 2025, on the occasion of World Microbiome Day.

About the Biocodex Microbiota Institute

The Biocodex Microbiota Institute is an international hub of knowledge dedicated to microbiota. The Institute educates the lay public and healthcare professionals on the importance of microbiota in healthcare and well-being.

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