The digestive tract is the main replication site of the human immunodeficiency virus (HIV), which is the cause of AIDS. The presence of HIV is associated with inflammation of the gut mucosa and an imbalance in the bacteria of the microbiota (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.   ) ), which could influence progression of the disease.

Not only bacteria in the microbiota... 

But what about the viruses which are present alongside bacteria, fungi, and archaea in the gut microbiota? Are they, like bacteria, involved in disease?

To answer this question, a team of Mexican researchers analyzed the ‘virome’ (viral component of the microbiota) in the feces of 92 HIV-positive individuals at different stages of infection but not receiving treatment and compared it with that of 53 healthy individuals. ¹

From the HIV-positive individuals, they then selected 14 people suffering from immunodeficiency, i.e. a low level of CD4 T cells, the cells in which HIV multiplies. 

They took stool and blood samples from them before antiretroviral treatment and at four timepoints during antiretroviral treatment. Their aim was to study changes in immunity and the gut microbiota during the first two years of therapy.

A striking expansion of certain virus species

They found that in those most affected by the disease, i.e. those suffering from severe immunodeficiency (CD4 T cell count < 350), three species of virus are present in great abundance in the microbiota: Anelloviridae (anelloviruses), Adenoviridae, and Papillomaviridae. Anelloviruses appear to be particularly affected by antiretroviral treatment, their markers decreasing significantly after 24 months of treatment. 

One notable finding was that the presence of anelloviruses at the start of treatment is associated with a poorer recovery of immunity and a lower CD4 T cell count, and therefore less effective treatment.

For the scientists, this study represents an important step forward. Not only does it provide a better understanding of the virome, a component of the gut microbiota little studied and less well understood than the bacterial component; it also provides a better understanding of the involvement of microbiota viruses in HIV infection.

Towards better monitoring of patients

These results open up the prospect of one day being able to use anelloviruses as a marker to predict the effectiveness of treatment and monitor the immune recovery of those affected by HIV. This is good news, since the fight against AIDS remains a major public health concern.

Extreme depletion of CD4 T cells, inflammation, bacterial dysbiosis, disruption of the epithelial barrier, microbial translocation... HIV’s impact on the gastrointestinal tract is now well documented. 

While no research has yet succeeded in defining a bacterial dysbiosis signature associated with HIV, we do know that enteropathy is involved in the chronic activation of the infection and in the development of immunodeficiency. 

Better understanding the role viruses play in the gut microbiota during HIV infection

The viral component of the gut microbiota is less well known than the bacterial component. To what extent does it play a part in this process? To find out, scientists in Mexico City investigated whether our ‘virome’ is associated with HIV infection and immunodeficiency. ¹

They began by comparing the CD4 T cell count and gut bacteriome and virome (viral RNA and DNA) of 92 untreated HIV-positive individuals with those of 52 healthy individuals at risk. 

To better understand the association between gut microbiota composition, HIV-related immunodeficiency, and immune recovery, they followed 14 HIV-positive individuals receiving antiretroviral therapy (ART) for two years. Blood and stool samples were taken at baseline (before ART) and at 2, 6, 12, and 24 months after the start of treatment.  

The results showed that HIV-positive individuals do indeed have reduced alpha bacterial diversity, with an increase in Enterococcus, Streptococcus, and Coprococcus in those at an advanced stage of infection. However, no clear signature could be identified.

Marked expansion of certain viruses

Compared with HIV-seronegative volunteers, individuals suffering from severe immunodeficiency (CD4 count < 350) showed radical changes in the composition of their gut virome:

• Increase in sequences of Anelloviridae (anelloviruses), Adenoviridae, and Papillomaviridae
• Decrease in plant viruses of the Tobamovirus genus

No Anelloviridae were detected in HIV-seronegative individuals.

The researchers believe that this expansion of viruses could contribute to the pathogenesis of AIDS by damaging the gut barrier and promoting inflammation.

The data also showed a striking link between HIV-associated immunodeficiency and the detection of Anelloviridae sequences, which were completely absent in the 53 HIV-negative individuals. In highly immunocompromised individuals, the abundance of anelloviruses decreased progressively during ART. 

A predictive tool?

Another finding: the detection of anelloviruses prior to treatment independently predicts poor immune recovery.

Despite the limitations of this study (majority of subjects male, dietary factors not taken into account, etc.), it suggests that the detection of anellovirus sequences in stool could be used to predict and monitor immune recovery during ART. 

Another step forward in our understanding of the gut microbiota, but above all a small step forward in the fight against HIV, a virus which, according to the WHO, affected 39 million people and caused 630,000 deaths in 2023. ²

Here's a quick look at Prof. Sokol best tips for a successful medical consultation

For a successful consultation:

• Avoid medical jargon as much as possible
• Use everyday life examples that can directly resonate with the patient
• Use illustrations to simplify the explanations of complex messages

Associated content

Group B Streptococcus (GBS) (sidenote: Group B Streptococcus (GBS) A bacterium commonly found in the gastrointestinal and vaginal tract of adults, which can cause severe infections in newborns if transmitted during delivery. ) , a bacterium quietly living in many women’s bodies, can turn deadly during pregnancy. Found in up to 40% of expectant mothers, GBS is typically harmless. But if transmitted during childbirth, it can cause life-threatening complications like sepsis, pneumonia, and meningitis in newborns. Groundbreaking research ¹ led by Toby Maidment at the Queensland University of Technology uncovers how the delicate balance of vaginal bacteria influences GBS’s behavior during pregnancy. The findings could change the way we think about prenatal care.

Good bacteria vs. bad news

In a study involving 93 pregnant women, researchers tracked vaginal bacteria at 24 and 36 weeks of pregnancy to see how microbial communities interact with GBS. One of the most surprising discoveries was the role of two types of bacteria: Lactobacillus crispatus (sidenote: Lactobacillus crispatus A beneficial bacterium in the vaginal microbiota that produces lactic acid, maintaining a low pH to prevent pathogen colonization and infections. ) and Lactobacillus iners (sidenote: Lactobacillus iners A less protective vaginal bacterium that produces only L-lactic acid, often associated with microbial imbalances and vulnerability to opportunistic infections ) . In women persistently colonized by GBS, L. Crispatus - a protective species that maintains vaginal acidity - was significantly reduced. Instead, L. iners, which is less effective at keeping harmful bacteria at bay, took over. This imbalance seemed to provide GBS the opportunity to stick around and thrive.

Meanwhile, women with only transient GBS colonization showed a more diverse microbial community at 24 weeks, with bacteria like Gardnerella vaginalis. By 36 weeks, this diversity declined, and L. crispatus and L. iners became dominant, correlating with the disappearance of GBS. This suggests that in some cases, the vaginal microbiome (sidenote: Vaginal microbiota The community of microorganisms residing in the vaginal environment, primarily dominated by Lactobacillus species, crucial for maintaining reproductive health. ) may naturally shift toward a healthier state - though it doesn’t always work when GBS is persistent.

What makes GBS stay or go?

Persistent GBS cases often involved the same bacterial strain sticking around through both timepoints, indicating a stable colonization. Interestingly, GBS levels in these cases dropped by about 11% as pregnancy progressed, likely due to hormonal changes that boost protective Lactobacilli. Yet, despite this decline, the persistence of L. iners continued to challenge the microbiome’s ability to fend off GBS effectively.

The future of prenatal care

This research opens the door to personalized interventions for GBS management. Probiotics that promote L. crispatus dominance or strategies to reduce L. iners might offer new ways to protect mothers and babies. With microbial profiling becoming more accessible, we could soon see targeted approaches to reduce GBS risks and improve neonatal outcomes.

Understanding the silent microbial battles within the vaginal microbiome is more than just scientific curiosity - it’s a matter of life and health for the most vulnerable. This study highlights how even the smallest organisms can have the biggest impact.

Group B Streptococcus (GBS) (sidenote: Group B Streptococcus (GBS) A bacterium commonly found in the gastrointestinal and vaginal tract of adults, which can cause severe infections in newborns if transmitted during delivery. ) , a bacterium often residing silently in the human body, can become a significant threat during pregnancy. Its asymptomatic colonization in up to 40% of pregnant women can lead to neonatal complications like sepsis, pneumonia, and meningitis if transmitted during delivery. New research, led by Toby Maidment from the Queensland University of Technology, explored the interplay between vaginal microbiota (sidenote: Vaginal microbiota The community of microorganisms residing in the vaginal environment, primarily dominated by Lactobacillus species, crucial for maintaining reproductive health. ) and GBS colonization over time, providing groundbreaking insights into microbial dynamics. ¹

Microbial shifts and persistent colonization

Using data from 93 pregnant women, they tracked microbial changes at 24 and 36 weeks of gestation, offering new clues about persistent and transient GBS colonization. One of the standout discoveries is the contrasting role of Lactobacillus crispatus (sidenote: Lactobacillus crispatus A beneficial bacterium in the vaginal microbiota that produces lactic acid, maintaining a low pH to prevent pathogen colonization and infections. ) and Lactobacillus iners (sidenote: Lactobacillus iners A less protective vaginal bacterium that produces only L-lactic acid, often associated with microbial imbalances and vulnerability to opportunistic infections ) . In women persistently colonized by GBS, L. crispatus, a key defender against pathogens, was significantly reduced. Instead, L. iners, a species less effective in maintaining vaginal acidity and microbial balance, was more abundant. This imbalance might create an environment that allows GBS to thrive.

Interestingly, transient GBS colonization (detected only at 24 weeks) was linked to more diverse microbial communities, dominated by species like Gardnerella vaginalis. By 36 weeks, this diversity declined, and L. crispatus along with L. iners became dominant, correlating with the resolution of GBS presence. This indicates a dynamic interaction where the vaginal microbiota may naturally shift toward a protective state, though not always effectively in persistent cases.

A closer look at GBS dynamics

Persistent GBS colonization often involved the same bacterial serotype across both time points, hinting at stable colonization mechanisms. Additionally, in persistently GBS-positive women, an average 11% reduction in GBS abundance was observed as pregnancy progressed, aligning with hormonal changes that increase Lactobacilli. However, despite this decline, the presence of L. iners continued to challenge the vaginal environment's resilience.

Before it’s too late!

This research presents a compelling case for personalized approaches to managing GBS in pregnancy. While L. crispatus emerges as a key player in vaginal health, L. iners seems less capable of offering protection against opportunistic pathogens. Understanding these dynamics could pave the way for interventions, such as probiotics targeted at increasing L. crispatus dominance or other strategies to bolster vaginal defenses.

Moving forward, microbial profiling may become a cornerstone of personalized obstetric strategies, potentially reducing the risks associated with GBS and improving neonatal outcomes.

We thought the younger generations had been successfully liberated by the feminist struggles of the 2000s, but they are proving even less comfortable than their elders when talking about female genitalia. And while forty-somethings scramble for intimate deodorants, under the influence of adverts promoting the freshness of their nether regions, the next generation, more mindful of their image, are turning to cosmetic procedures, like vulvoplasty (sidenote: Vulvoplasty Plastic surgery of the vulva, to increase or reduce the size or volume of the labia majora. ) ¹. Each generation has its own unique relationship with intimacy, it would seem. Regardless, the hygiene and health of this fragile body area should concern us at all ages... hence these few cheeky reminders, to lift the veil on any taboos.

The female genitalia is both a terra incognita in terms of anatomy and a taboo in terms of conversation, including among women. So much so that health professionals struggle to understand their patients’ ailments due to insufficiently clear explanations, and/or because they confuse the vulva (external part of their genitalia) with their vagina (internal part)¹.

Now that we’ve come this far, we might as well explain all the other orifices. From front to back, the female genitals include three openings, in this order:

• the urinary meatus, connected to the bladder (which stores urine) by a canal called the urethra (which allows urine to be evacuated outside the body during urination)²,
• then the entrance to the vagina (reproduction)
• then the anus (stools).

We speak also of:

Our intimacy is no exception; like other organs, it is home to several microbiotas, which are:

Vulvar, vaginal and perianal microbiotas evolve over time. For example, the vaginal microbiota is influenced by age, sex hormones and external factors such as pollution, stress, antibiotics, etc⁴. Imbalances can occur: after menopause, the drop in estrogen leads to a loss of lactobacilli and therefore a rise in pH, resulting in frequent vaginal dysbiosis⁷. As for the anal microbiota, it depends above all on diet and stress: excessive anxiety induces an inflammatory response that favors the development of pathogenic bacteria in the digestive tract... which end up in the perianal area¹.

The proximity of the urinary, vaginal and anal orifices also explains possible “exchanges” of flora between the 3 microbiotas in these 3 areas... and the possible invasion of the vaginal microbiota by digestive Escherichia coli that may have ventured beyond the perianal area¹.

Paradoxically, inappropriate intimate hygiene practices can actually encourage exchange and imbalance. Washing the vulva too aggressively (with unsuitable products) or too frequently (more than once a day) can quickly damage the skin barrier function in this very fragile and reactive area. Water alone can be enough to dry it out and expose it to itching and burning⁸. And the perfumed soaps, intimate sprays, lubricants, deodorants, etc. that some women self-prescribe in an attempt to treat odors, itching, pain and dryness are counterproductive⁴.

Another common error: waxing or shaving the entire vulva^1,9. This is a fashion phenomenon that concerns 84% of premenopausal American women, for 2/3 of whom it is a daily or weekly routine. Often justified on hygienic grounds, the reverse is actually true: it creates lesions that make it easier for bacteria and viruses to enter. Alterations in the vaginal microbiota have in fact been observed in women opting for full vulva hair removal⁹.

Finally, wearing very tight, synthetic clothing seems also to encourage the development of pathogens (a warmer, more humid environment), resulting in more frequent itching and urogenital problems¹.

Why is there such a gap between practices and recommendations? There are undoubtedly many reasons for this:

• too few women are informed by their doctors about good practices: 52% of women surveyed said they had never received such information, and 25% had only been informed on one occasion by their health practitioner¹⁷;
• the frequent confusion between vulva and vagina means messages are misunderstood;
• the stupidest myths are often those that stick most¹.

This problem is all the more important when you consider that the vulva is the first line of defense in a woman’s genital system¹⁰.

The right way to preserve the microbiota and the delicate protective hydrolipidic film of female genitalia. A routine that respects the balance of the vulva, with products adapted to the age and specific needs of each woman.

In all cases, there are 3 main immutable principles^₁₀:

• external washing only (= vulva, no vaginal douching), from front to back (vulva then anus)
• without a washcloth (which may contain bacteria), but with clean hands,
• once a day. Only women suffering from frequent diarrhea can justify more frequent external washing (due to more frequent bowel movements). Or during menstruation, when you may need to wash the intimate area a second time during the day.

Healthy vaginal microbiota depends on good intimate hygiene. But sometimes that’s not enough, and a little help may be needed to boost the good bacteria in your microbiota, with: 

We know that in pre-menopausal women, increased diversity in the vaginal microbiota and a loss of Lactobacillus dominance are associated with greater mucosal inflammation. This leads to a higher risk of dysplasia and cervical infection.

A US study ¹ on 119 post-menopausal women (average age 61 at inclusion) seeking treatment for moderate to severe vulvovaginal discomfort (irritation, dryness, etc.) sought to answer this question.

119 post-menopausal women

The subjects were divided into three groups based on the treatment received and were followed for twelve weeks. The three treatments were as follows:

1. estradiol tablet and placebo moisturizing gel
2. placebo tablet and moisturizing gel
3. double placebo

At baseline, 29.5% of participants had their vaginal microbiota dominated by lactobacilli.

Caucasian women were less likely to have this protective flora. Overall, lower Lactobacillus dominance and lower alpha diversity in vaginal fluids were associated with lower concentrations of inflammatory immune markers, while complete loss of Lactobacillus dominance was associated with higher concentrations of pro-inflammatory cytokines (sidenote: Cytokine A small protein involved in communication between cells, especially in the immune system.  Cytokines: Introduction_British Society for Immunology ) , as observed in previous studies on post-menopausal women.

Lasting support from lactobacilli

This mirrors the tendency reported in women of childbearing age. Lactobacilli may thus continue to play a protective role after menopause, with beneficial effects on the immunity of the vaginal mucosa by helping to reduce inflammation – or at the very least, by being associated with this decrease.

Conversely, an increase in the alpha diversity of the vaginal microbiota is thought to be associated with pro-inflammatory cytokines. 

Mucositis (sidenote: Oral mucositis Acute, painful inflammation of the oral mucosa, often induced by anti-cancer treatments such as chemotherapy and radiotherapy. Symptoms include redness, pain, and ulceration, and can be accompanied by dry mouth, altered taste, and difficulty in eating. It can lead to malnutrition, dehydration, and reduced quality of life. Treatment is symptomatic and aims at relieving pain, promoting healing, and preventing infection. Explore Cleveland Clinic ) is a common side-effect of chemotherapy and radiotherapy. It is characterized by inflammation of the oral and intestinal mucosa.

The result is lower quality of life for patients, poorer compliance with treatment, feeding difficulties, and complications that are all the more serious when the patient is frail. Since current therapies only treat symptoms, modulating the oral microbiota seems to be a promising new approach.

Following on from work suggesting a link between oral microbiota and the development of chemotherapy-induced mucositis, the publication at the end of 2024 of a pediatric clinical case has increased our hopes.

Decision and transplantation protocol

The story relates to a six-month-old Russian girl, diagnosed at the age of four months as suffering from a retroperitoneal neuroblastoma with multiple metastases. Chemotherapy was rapidly complicated by various side effects, including severe oral mucositis, rapid weight loss, and C. difficile infection.

The doctors decided to perform a transplant of the healthy 33-year-old mother’s oral microbiota. The donation samples were spread out over the day (nine samples of 1.5 mL), away from meals and tooth brushing.

Oral transplantation

During each of the following three cycles of chemotherapy (the dosage of which was reduced), the infant received her mother’s saliva in her mouth (13.5 mL per day for 10 days) some thirty minutes after breast-feeding.

After six chemotherapy cycles, the patient underwent a complete resection of a retroperitoneal tumor along with right-sided adrenalectomy, followed by high-dose chemotherapy with subsequent autologous hematopoietic cell transplantation (auto-HCT). A final oral transplant of maternal saliva was performed prior to the auto-HCT.

Effects on mucositis

Oral microbiota transplantation effectively prevented the development of mucositis following three new cycles of chemotherapy, and only grade 1 oral mucositis developed after auto-HCT. In all parts of the mouth, there was a decreased abundance of bacteria from the Staphyloccaceae, Micrococcaceae, and Xanthomonadaceae families. Conversely, there was an increase in the relative abundance of Streptococcaceae and certain other bacterial taxa. 

Maternal saliva transplantation thus appears to have prevented further severe mucositis in the patient, and to have been accompanied by a change in oral microbiota composition. No adverse events due to the transplantation of maternal saliva were noted.

A healthy vaginal microbiome, typically dominated by Lactobacillus (sidenote: Lactobacillus A group of beneficial bacteria commonly found in the vaginal microbiome. They produce lactic acid, helping maintain a low pH to protect against infections. ) species, is central to gynecological health. Yet, the mechanisms through which these microbes modulate inflammation have long eluded researchers. A new study ¹ led by Virginia J. Glick, published in Cell Host & Microbe, unveils that certain strains of Lactobacillus crispatus produce β-carboline alkaloids - small molecules that exhibit targeted anti-inflammatory properties.

This discovery offers a fresh perspective on how these bacteria contribute to immune homeostasis and sets the stage for potential therapeutic applications.

β-carbolines: Precision immunomodulators

The study identified β-carboline compounds, including perlolyrine (BC6) (sidenote: Perlolyrine (BC6) A potent β-carboline compound identified in Lactobacillus crispatus that reduces inflammation while preserving immune defense. ) , as potent suppressors of inflammatory signaling. Using a dual reporter system in human monocyte-derived THP1 cells, researchers demonstrated that L. crispatus-derived β-carbolines inhibited NF-kB and type I interferon (sidenote: Interferon (IFN) Signaling A key immune pathway that fights infections but can drive inflammation when overactive. ) (IFNAR) pathways. These molecules uniquely suppressed pro-inflammatory cytokine production in immune cells while leaving antiviral responses intact in epithelial and barrier cells - a level of selectivity rare among anti-inflammatory agents.

Notably, this is the first time that β-carboline, previously linked to plants and soil microbes, have been identified as products of vaginal Lactobacillus strains. Their discovery highlights a new dimension in microbiota-host interactions. Furthermore, cervicovaginal lavage samples from individuals with healthy vaginal microbiomes (low Nugent scores (sidenote: Nugent score A diagnostic scoring system used to assess bacterial vaginosis based on the presence and proportions of certain bacteria in a Gram-stained vaginal sample. ) ) were significantly enriched with β-carboline compared to those with bacterial 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. ) (high Nugent scores), underscoring their potential as biomarkers for microbiome health.

Translating science into therapeutics

To explore the clinical relevance of these compounds, researchers applied BC6 topically in a mouse model of vaginal inflammation induced by herpes simplex virus-2 (HSV-2). The results were striking:

• BC6 significantly reduced inflammation
• Dampened pro-inflammatory cytokines like IL-1β and IL-18
• And improved disease scores without affecting viral titers

The treatment maintained innate immune cell populations while decreasing the inflammatory signaling driving tissue damage.

Even more intriguing, some mice pre-treated with L. crispatus supernatant remained asymptomatic despite similar viral burdens as untreated controls. This suggests a role for these compounds in enhancing disease tolerance - a concept gaining traction in immunological research.