Rather than “feel good in your skin”, should we be saying “feel good in your skin microbiota ”?

So suggests a British study, linking psychological well-being to the microorganisms living on our skin, specifically the skin of the face, scalp, forearms, and armpits, based on a study of 53 Britons with an average age of 63. This research highlights a system of interactions between the skin and the brain, echoing the now familiar dynamics of the gut-brain axis.

More Cutibacterium, more well-being?

The study shows for the first time an increased abundance of certain bacterial genera in those who feel the best in their skin, both in terms of general well-being and the well-being of the skin area in question. The skin bacterium most common to Britons who feel the most comfortable in their bodies is Cutibacterium (sidenote: Cutibacterium A bacterial genus whose classification has been significantly revised in recent years (until 2016, it was known as Propionibacterium). The genus includes several species, including the infamous C. acnes (an opportunistic pathogen involved in acne and infections of breast implants, shoulders, etc.), as well as C. avidum, C. granulosum, C. namnetense, and C. humerusii Ahle CM, Feidenhansl C, Brüggemann H. Cutibacterium acnes. Trends Microbiol. 2023 Apr;31(4):419-420. ; CTCB ) . Do you have plenty of it on your face? Then you must be fairly stress-free. If your armpits are teeming with it, your mood is likely to be good and your stress levels low. Conversely, a lower abundance of Cutibacterium may contribute to disorders such as stress, anxiety, or depression.

This is somewhat surprising, since Cutibacterium is usually associated with C. acnes and the puberty nightmares that come with it, rather than elderly Britons enjoying their golden years. This bacterium could also promote positive skin health by inhibiting pathogens and regulating skin acidity, thanks to its ability to convert sebum into free fatty acids.

Cause or effect?

The central question is, as always, whether the presence of Cutibacterium is a cause or effect of well-being. In other words, does the presence of Cutibacterium make us happy, or does a cheerful disposition attract Cutibacterium to the skin? Or could it be a third factor common to both, such as lifestyle, exercise, or diet?

At present, we can’t say. We do know that the skin and its microbiota act as a protective barrier for the body, inhibiting pathogens, and thus providing security and peace of mind. Conversely, it has been shown that stress, anxiety, and depression can impact our skin, leading to skin disorders such as eczema (or atopic dermatitis), psoriasis, acne, and underarm odor.

We’ve heard of the gut-brain axis, and now we know there’s a bidirectional skin-brain axis as well, with the former influencing the latter and vice versa. For the first time, a link has been found between skin microbiota and psychological well-being. This should encourage psychodermatology (sidenote: Psychodermatology Psychodermatology is a relatively new field of medicine. It encompasses the interaction of mind and skin. Treatment of psychodermatological disorders focuses on improving function, reducing physical distress, diagnosing and treating depression and anxiety associated with skin disease, managing social isolation and improving patient’s self-esteem. Both pharmacological and psychological interventions are used in treating psychodermatological disorders. Explore Jafferany M, Franca K. Psychodermatology: Basics Concepts. Acta Derm Venereol. … ) research to further study the bacteria involved and their potential influence on our skin and general health.

What do we already know about this subject?

The vaginal microbiota plays a key role in defending against pathogens, maintaining mucosal immunity, and supporting reproductive health. Dominance by Lactobacillus species, especially L. crispatus, maintains a low pH and inhibits pathogenic colonisation² . Dysbiosis — defined by a loss of lactobacilli and overgrowth of anaerobic species such as Gardnerella or Prevotella — is associated with increased risks of bacterial vaginosis (BV), preterm birth³ , infertility⁴, sexually transmitted infections, human papillomavirus (HPV) infections and gynaecological cancers⁵ . Previous studies have shown that hormonal changes, menstruation, and sexual intercourse can influence the composition of the vaginal microbiome⁶. Many of these studies relied on infrequent sampling and lacked resolution to assess short-term fluctuations or determine the drivers of transitions between eubiosis and dysbiosis. The contributions of viral dynamics and functional bacterial genes have remained largely unexplored.

What are the main insights from the study?

This study introduces the concept of VCDs, offering a new framework for classifying microbiome behaviour across the menstrual cycle. Unlike community state types (CSTs), which describe static microbiome compositions, VCDs capture temporal patterns that may better reflect microbiome resilience and vulnerability. The four VCDs — constant eubiotic, constant dysbiotic, menses-related dysbiosis, and unstable dysbiotic — represent distinct profiles of microbial stability. Women in the constant eubiotic group maintained Lactobacillus dominance throughout the cycle, while those with constant dysbiosis had persistent BV-associated communities. Menses-related dysbiosis was characterised by temporary shifts during menstruation, often reverting mid-cycle, whereas the unstable group experienced abrupt fluctuations after exposures like sexual intercourse, suggesting greater ecological fragility.

One of the key findings was that instability in the vaginal microbiome is associated with increased bacteriophage activity and a higher prevalence of L. iners. This species is frequently linked to transitional or less stable states, and phage abundance may reflect active lytic cycles that destabilise dominant bacteria via “kill-the-winner” dynamics. Additionally, women with transient dysbiosis showed increased abundance of potential pathogens such as Sneathia spp. during and after menstruation, pointing to specific periods of vulnerability.

Strain-level analysis revealed differences in bacterial gene content, including bacteriocins produced by Gardnerella leopoldii that may inhibit lactobacilli. These genes were more prevalent in unstable and dysbiotic VCDs, supporting a possible mechanistic role in shaping community structure. Although these genetic findings require further validation, they highlight the importance of moving beyond species-level classification to understand microbial function and its impact on host health.

What are the consequences for clinical practice?

This study underscores the need to rethink how vaginal health is assessed and monitored in clinical practice. The recognition that vaginal microbiota are dynamic — and that stability patterns differ markedly between women — has implications for diagnostics, risk assessment, and therapeutic strategies. Sampling at a single time point, especially during menstruation, may fail to capture meaningful fluctuations or misrepresent a woman’s baseline microbial state. Clinicians should consider collecting samples at multiple points in the cycle to better assess microbiome behavior, particularly in patients with recurrent symptoms or reproductive concerns.

The limitations of CST-based classification are evident in this study. Two women with the same CST may exhibit entirely different VCDs, one with stable eubiosis and the other with frequent dysbiosis. Incorporating VCD assessment could enable more personalised interventions, such as recommending prophylactic microbiome support for women with unstable patterns or targeting high-risk windows (e.g. post-menses) for infection screening.

The identification of phage-driven instability and strain-level bacterial traits opens avenues for precision medicine. Future therapies may need to address microbial function — such as biofilm formation or bacteriocin production — rather than composition alone. Understanding the dynamics of vaginal bacteriophages could also inform novel microbiome stabilisation strategies.

Figure 1. Vaginal time series can be classified into four categories (Vaginal Community Dynamics) according to their proportions of eubiotic samples

a. A decision tree can separate a time series of samples into dynamic groups, based on the community state types (CSTs). Input from the user determines which CSTs are considered eubiotic (here: I, II, and V) and which days are to be considered free from the influence of menses (here: cycle day 9 to cycle day 25). Time series with ≥80% eubiotic samples are considered constant eubiotic; conversely, those with >80% dysbiotic samples are considered constant dysbiotic. For those in the 20–80% range, a second assessment is done on the days free of menses: if they are >80% eubiotic, the time series is considered menses-related dysbiotic, and otherwise unstable (changing from eubiosis to dysbiosis without a clear temporal pattern). b. A colour map with one individual per row and one day per column. The colour of each intersection depicts CST. Coloured bars on the left side show the vaginal community dynamics of each woman. c. Additional colour bars show the inferred vaginal community dynamics of each participant when using fewer samples for classification. Reproduced from Hugerth LW, et al. Microbiome 2024, 12, 1531 (doi:10.1186/s40168- 024-01870-5) under a CC-BY 4.0 license (creativecommons.org/licenses/by/4.0). No changes have been made to the figure.

The classification tool VALODY, designed to assign VCD categories based on VALENCIA CST assignments, is available on GitHub at https://github.com/ctmrbio/valody.

How the menopausal microbiome impacts women’s overall health

Menopause-induced changes lower gut microbiome diversity and cause a shift toward greater similarity to the male gut microbiome. This review details the healthrelated consequences of these changes. During perimenopause, a gradual decline in hormone levels disrupts the gut microbiome balance and contributes to adverse health outcomes, including cardiometabolic disease and changes in oestrogen metabolism. Hormonal fluctuations during menopause change the oral microbiome, heightening the risk for dental caries, periodontitis, and oral infections such as candidiasis. Menopauseinduced vaginal microbiota alterations increase susceptibility to bacterial vaginosis, vulvovaginal atrophy, and recurrent urinary tract infections. Menopause also alters the diversity and abundance of gut microbiota that have been linked to inflammation. Chronic dysbiosis-induced inflammation predisposes menopausal women to metabolic disorders and autoimmune diseases.

This article bridges the gap between endocrinology and microbiology, and emphasises the systemic impact of menopause beyond reproductive health. A key strength of the review is its holistic examination of menopausal-related hormonal fluctuations with corresponding shifts in gut and vaginal microbial composition and diversity. This opens the door to exploring microbiome-based biomarkers for managing menopausal symptoms such as genitourinary syndrome, metabolic changes, or inflammation. This article’s interpretation of age-related changes in women’s health enriches the growing interest in the human microbiome’s role in disease. While hormone replacement therapy has shown promise in mitigating some of the adverse effects of oestrogen deficiency, its broader application is limited by its systemic risks. The targeted use of specific probiotics to restore gut microbial balance, coupled with dietary and lifestyle modifications, may offer safer, more individualised alternatives that mitigate adverse health effects of menopause.

Menopausal microbiome research is overrepresented with data from Western populations and a lack of detailed mechanistic insights. Since diet, lifestyle, and environmental factors significantly influence the microbiome, we need ethnically and geographically diverse research incorporating advanced “omics” approaches to fully elucidate these influences. More effective, personalised treatment strategies will then emerge that can improve the quality of life for menopausal women.

In conclusion, menopause is a whole-body transition involving significant changes in the microbial ecosystem. Understanding and addressing these changes can enhance patient outcomes and promote healthier ageing in women.

Gut microbiota composition in women with polycystic ovary syndrome

The gut microbiota is increasingly viewed as an invisible organ-like system that not only plays an important role in a woman’s wellbeing but also affects the pathophysiology of some disorders such as polycystic ovarian syndrome (PCOS). Knowing about microbial metabolite pathways may elucidate effective treatments.

A recent meta-analysis that included 948 women with PCOS from 14 studies explored the relationships between gut microbiota among women from different regions and with different testosterone levels. Key findings revealed distinct gut microbiota compositions in PCOS patients compared with their healthy counterparts, and significantly different gut microbiota between PCOS patients with higher testosterone levels and those with lower testosterone levels. Also, gut bacterial genera differed among PCOS patients from different regions; European patients had high Alistipes levels, whereas Chinese patients had high Blautia and Roseburia levels.

These findings support current evidence showing that PCOS patients have fewer different types of bacteria and a less balanced microbial community compared with healthy women. The data also confirm the abundance in PCOS patients of specific bacterial genera such as Escherichia/Shigella and Alistipes, which are associated with insulin resistance and inflammation. This study implies that the gut microbiome is linked to various metabolic and hormonal disturbances associated with PCOS, which is compatible with previous research. Importantly, it demonstrates differences in bacterial taxa between Chinese and European women with PCOS, which may assist with personalised treatment strategies. Further research to determine PCOS-associated bacteria strains may enhance anti-PCOS microbial therapies and studies in different geographical regions would promote the global treatment of PCOS.

To conclude, characterising gut microbiota in PCOS patients from different countries may enable gut microbiota to act as a biomarker to distinguish different subtypes of PCOS, and thereby improve the clinical diagnosis and treatment of PCOS.

The role of the vaginal microbiota in women’s health

The human body hosts trillions of microorganisms, collectively known as the microbiome, residing in various locations and coexisting in a complex symbiotic partnership. Importantly, the vaginal microbiota influences women’s reproductive and overall health. Understanding this ecosystem could revolutionise the prevention and treatment of these conditions.

This review highlights the links between dysbiosis of the vaginal microbiota and gynaecological disorders, as well as pregnancy-related complications. Specifically, reductions in lactobacilli and an increased vaginal microbiota diversity are associated with human papillomavirus (HPV) infection, the formation of cervical lesions, and cervical cancer. A loss of vaginal Lactobacillus dominance can create a proinflammatory environment that compromises successful embryonic implantation, leading to infertility. An imbalance in the vaginal microbiome can trigger inflammation leading to pregnancy complications. Having fewer Lactobacillus species in the vaginal microbiome increases the risks of premature rupture of membranes, preterm birth, miscarriage, and ectopic pregnancy. Vaginal dysbiosis may contribute to insulin resistance, a hallmark of gestational diabetes mellitus, and greater diversity in bacterial composition has been found in severe preeclampsia. Testing for Prevotella bivia colonisation during pregnancy may help to predict and mitigate against hypertensive disorders during pregnancy.

This review underscores the key relevance of the vaginal microbiome in women’s reproductive and overall health. The composition of this microbiome can impact everything from fertility and pregnancy outcomes to infection susceptibility. The article covers various aspects of vaginal microbiota, including its relationship with immune system function, inflammation, and pathogen defence, and thereby offers a broad, holistic understanding of its role with generalisable insights into women’s health at large. Enhanced knowledge around how the vaginal microbiome influences health presents an important advance for early disease detection and prevention, instead of treating infections or conditions after they appear. However, long-term study data are needed to clarify the long-term effects of vaginal microbiome imbalances. Moreover, while probiotics and other microbiomebased interventions show promise for maintaining a healthy vaginal microbiome, probiotic strains, dosages, and delivery mechanisms have yet to be standardised for clinical application. Much work remains to be done.

In sum, having fewer vaginal Lactobacillus species and increased vaginal microbial diversity is associated with obstetric and gynaecological complications. This review highlights the possibility of using microbiome-based diagnostics to detect imbalances in vaginal flora, potentially before symptoms manifest. Early intervention may prevent adverse consequences.

Talk about vaginal infections, fertility, or pregnancy complications often focuses solely on women. But there is another important player: the male urogenital tact (MUGT). The wide variety of microbes in the MUGT can significantly affect female reproductive and vaginal health (Figure 1). Understanding these influences may improve outcomes for women, especially those with persistent vaginal infections, fertility challenges, and pregnancy complications.

Figure 1. Consequences of exchanges of bacteria associated with vaginosis during sexual contact between males and female

What do we know about the male genital microbiota?

The MUGT includes several distinct microbial environments: the skin of the penis, the urethra, semen, and the urinary tract. Each has a unique bacterial community, influenced by factors like circumcision, sexual practices, hygiene, and lifestyle.

MUGT microbiota vary with circumcision status, sexual practices, and the composition of the female partner’s vaginal microbiota⁷.
Interestingly, the urethral microbiota of homosexual men does not seem to be modified by the type of sexual intercourse (oral or anal)⁸. Bacterial exchanges between partners during sexual contact are the rule; why these exchanges lead to vaginal dysbiosis in some cases and not others is unclear.

Seminal microbiota are also influenced by several physiological functions (age, hormonal changes) and lifestyle or epigenetic factors
(tobacco, alcohol, obesity, high-fat diet, exposure to toxins)⁵. These modifiable factors are potential targets for intervention.

How does the MUGT impact female health?

The transmission of microorganisms responsible for bacterial and viral sexually transmitted infections (STIs) including HIV and herpes simplex virus infection during sexual contact is the most obvious consequence of how the MUGT impacts female health. The female complications of bacterial STIs (gonorrhoea, infections by Chlamydia trachomatis or M. genitalium) are well known (inflammation and infection of the upper genital tract, risk of tubal infertility).

Many studies have shown that the epidemiological profile of women with BV is comparable to that of women with STIs, suggesting possible sexual transmission of the bacteria involved in BV. The presence of BV-associated bacteria in the foreskin and urethra of partners of women with BV and a concordance of vaginal and male urethral bacterial strains support the sharing of these strains or sexual transmission of BV.

Treating the male partner with oral antibiotics (metronidazole) has had very limited impact on recurrence rates in women with recurrent
BV, although combining metronidazole with a topical antibiotic applied to penile skin in partners of women with BV may reduce the risk of recurrence⁹.

The impact of the MUGT on uterovaginal health is not limited to passive bacterial transfer. Seminal fluid contains proinflammatory substances (such as prostaglandins) that can interfere with immune responses and inflammation within the female genital tract¹⁰.

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!