For the first time⁹, scientific data were obtained regarding the cervicovaginal microbiota in postpartum HIV-positive women. They showed that postpartum HIV-positive women have a highly diverse microbiota, just like postpartum HIV-negative women. They also showed that immunodeficiency caused by HIV and cervicovaginal dysbiosis are suspected to play a role in the onset of precancerous lesions.

HIV and increased risk of lesions

Vaginal microbiota dominated by Lactobacillus crispatus is associated with a decreased risk of HIV infection and, in HIV-positive women, to a decreased risk of HPV infection. On the contrary, vaginal dysbiosis with higher bacterial diversity and decreased levels of lactobacilli increases the risk of HIV and HPV acquisition, cervical precancerous lesions and cervical cancer. It is also known that a change in vaginal microbiota composition occurs during the postpartum period: higher bacterial diversity and decreased levels of Lactobacillus crispatus. As a result, postpartum HIV-positive women have a vaginal microbiota that could expose them to a higher risk of HVP infection and thus to a higher risk of cervical precancerous lesions and cervical cancer.

What is the role of the microbiota?

To test this hypothesis, Brazilian researchers analyzed the vaginal microbiota of 80 young HIV-positive women on antiretroviral therapy at 6 and 12 months postpartum: four types of microbiota were identified, including three with a high microbial diversity, but none dominated by Lactobacillus crispatus. The researchers observed an overabundance of specific bacteria in cases of cervical precancerous lesions, especially Moryella and Schlegellela. They also detected an increased content of Gardnerella vaginalis in women whose lesions had regressed during the monitoring period, but not in women who had developed lesions

It is not clear from these findings whether the identified bacteria are the cause or the result of cervical precancerous lesions, but this study still highlighted HIV-positive women’ susceptibility and described the type of microorganisms involved. Their exact role in the development of lesions has yet to be determined, bearing in mind that cervical cancer is the 4th most common type of female cancer, causing more than 200,000 deaths every year in the world.

The composition of the vaginal microbiota changes throughout women’s lives: while it has a particularly low content of Gardnerella vaginalis, Prevotella and lactobacilli before puberty, it becomes almost exclusively colonized by lactobacilli after puberty. Lactobacilli ensure women’s health by fighting against pathogens. Their decrease is associated to various gynecological disorders, such as premature delivery, infertility, sexually transmitted infections or even pelvic inflammatory diseases. Shortly before menopause, hormonal variations cause significant changes in the composition of the vaginal microbiota which finds a different balance after menopause.

Microbes and reproduction

Vaginal microbiota also seems to play a role in conception, whether it is natural or by means of in vitro fertilization (IVF). The presence of Gardnerella vaginalis and Atopobium vaginae in the vaginal microbiota was associated to lower success rates, while treatment of bacterial vaginosis, which is frequent in infertile women, improves pregnancy rate. Success also depends on the proportion of lactobacilli in seminal fluids as well as the presence of some species in the Fallopian tubes and the uterine mucosa (endometrium), whose microbiota could either favor or limit chances of embryo implantation.

The baby’s health starts in the uterus

The baby’s immune and metabolic systems could be determined during intrauterine life through its exposure to maternal microbes which are present in the placenta and amniotic liquid and can also be found in the newborn’s first stools (meconium). At present, it is unknown if the placenta hosts its own microbiota. It is known however, that it is similar to the maternal oral flora, which could explain why pregnant women with periodontal diseases have an increased risk of facing pregnancy-related complications. Moreover, changes in its composition are associated to premature births.

Risks and benefits

Although the mother is a source of microbes for her baby, other factors come into play to modulate the baby’s microbiota. Use of antibiotics by the mother (especially in the second or third trimesters of pregnancy) as well as cesarean delivery (because the newborn does not come into contact with the mother’s vaginal microbiota) are associated with an increased risk of childhood obesity. On the contrary, probiotics seem to benefit the mother and her unborn child, according to the researcher Jessica Younes. In pregnant women, they could reduce the risk of premature delivery, gestational diabetes, postpartum depression or urinary and vaginal infections; whereas in the newborn child they could limit colic, predisposition to developing allergies (atopy), resistance to antibiotics and could also reduce— or even eliminate—the risk of necrotizing enterocolitis which is a fatal disease. Finally, breastfeeding or formula feeding could play a significant role in the child’s microbiota composition, although its impact on childhood health remains unknown.

A healthy vaginal microbiota is composed of various microorganisms, where lactobacilli generally predominate. However, advances in molecular biology have shown that not all lactobacilli provide the same degree of protection: Lactobacillus crispatus, for example, is associated to an anti-inflammatory profile and seems to afford protection against pathogenic germs. On the contrary, Lactobacillus iners seems to promote an imbalance of the vaginal microbiota (dysbiosis) favorable to bacterial vaginosis, similarly to pathogenic bacteria

Microbiota, vaginosis and STIs: dangerous liaisons

Vaginosis, vaginal candidiasis, colonization of the vaginal microbiota by pathogens, and STIs share many biological and behavioral factors which could explain their interrelationships. Although vaginosis and vaginal candidiasis are not STIs per se (since they can occur without intercourse), a study by Janneke Van de Wijgert showed that sexual transmission of the responsible organisms most certainly plays a role in their development. Moreover, dysbiosis and vaginosis weaken the vaginal mucosal barrier and leads to cervicovaginal inflammation, which increases the risk of HIV infection. The risk of contracting sexually transmitted infections thus depends, at least in part, on the health of the vaginal microbiota. By preserving their microbial flora, women could limit their risk of developing STI. Future research needs to focus on determining how the vaginal microbiota can expose women to a higher risk of STI, in order to better screen and treat them, especially with local probiotics.

Escherichia coli is naturally present in our intestinal microbiota but can become a pathogen by using some of its infectious properties such as the ability to adhere to the bladder. It is then referred to as uropathogenic Escherichia coli (UPEC). Urinary tract infections occur when the urogenital area is contaminated by the fecal flora. Bacteria can colonize the urethra exclusively (causing urethritis), spread to the bladder and cause acute cystitis, or reach the kidneys (causing pyelonephritis). This bacterial migration from the anal area to the urogenital system raises two questions: are the responsible strains different from a genetic standpoint or do they need to adapt when they migrate from the intestines to the bladder? For preventive purposes, could it be possible to predict the risk of contracting a UTI using fecal Escherichia coli samples?

No adaptation is required

Several studies^{4, 5} from a Danish team provided us with some answers. The researchers observed that the fecal strains of Escherichia coli in patients with UTI were the same as those found in their own urine samples and also the same as in healthy women. The only differences were a few minor genetic variations. In other words, Escherichia coli is able to migrate from the intestines to the bladder without needing to adapt at all. The evidence thus showed that fecal microbiota composition cannot predict the risk of developing a urinary tract infection. Then, what are the causes of UTIs? UPEC-mediated urinary tract infection probably results from a combination of factors related to the bacteria (ability to adhere to intestine cells, virulence...) and to the host’s immune status, creating an infection-prone environment

Although it affects nearly 20% of women in France¹ and millions of women every year in the world, bacterial vaginosis remains under-diagnosed and poorly treated because of its unclear definition.

Bacterial vaginosis has been described as an infection, an inflammatory disease, a dysbiosis (microbiota imbalance), a syndrome, or even a normal situation. A proper definition has not yet been found and it keeps causing controversy among the scientific community. Canadian microbiologist, Gregor Reid² reminded that while the disease had been discovered in 1954 and defined as an infection caused by Gardnerella vaginalis, the term “bacterial vaginosis” only appeared in 1983. But the fact that the responsible bacterium can also be found in healthy women without causing vaginosis undermines this theory. Six years later, vaginosis was described as “a complex change in vaginal microorganisms associated with malodorous discharge and no visible inflammation”. Some time later, researchers observed an increase in inflammation markers and classified it as an inflammatory disease. However, this definition was invalidated in 2010 due to lack of evidence. More recently, the term “dysbiosis” was added to the list. In conclusion, after nearly 65 years of research, no consensus has been reached yet.

Poorly defined, poorly treated

According to the literature, vaginosis is not a disease as generally understood, that is to say a deterioration of health characterized by specific signs. It presents as a range of symptoms (inflammation, foul vaginal odor, increase in bacterial diversity, etc.) which vary greatly from one woman to another. In some cases, it may cause no symptoms at all. Nevertheless, its diagnosis, prevention and management depend on its definition. To this day, only a pharmacologic approach receives financial support from health authorities, thus excluding alternative avenues aiming at restoring and maintaining the flora, such as probiotics and prebiotics. Gregor Reid believes this to be an aberration and calls for the term “vaginosis” to be abandoned and replaced by a term which better describes the different disorders it encompasses. According to him, “vaginal dysbiosis” or “vaginal inflammation” would help provide a more appropriate treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting joints and characterized by synovial membrane inflammation which reaches surrounding bones and cartilages. For some years the gut microbiota has been the focus of increasing interest from the scientific community, who believes it is involved in RA.

Dysbiosis observed as soon as the early stages

While previous works had already reported dysbioses in patients at an advanced stage of the disease, a Korean team focused on the early stages, and exclusively on women, who are more affected by RA. The 29 female patients included in the study were either at a preclinical stage (PC, n=17), or with clinically apparent early-stage RA (ER, n=12), and were DMARD-naive (DMARD = disease-modifying antirheumatic drugs). The bacterial DNA from fecal samples extracted from patients was compared to that of 25 control healthy women. First finding: the microbiota of patients with RA was characterized by a lesser bacterial diversity (without any difference between PC and ER patients). Moreover, differences were observed in the present bacterial species: for instance, bacteria from the Bacteroidetes phylum were over-represented in patients with RA, while those from the Actinobacteria phylum were under-represented, especially those from the Collinsella genus.

Altered genetic functions

These differences in composition were reflected in genetic differences: genes involved in the synthesis of ubiquinone (co-enzyme Q10) and menaquinone (vitamin K2) were more abundant in controls, while genes involved in the transport and absorption of iron were more abundant in patients with RA. This characteristic, which promotes the absorption of iron by bacteria from the microbiota, could explain the anemia often observed in people with RA. Finally, genes coding for the synthesis of lipopolysaccharides–molecules expressed on the surface of gram-negative bacteria which cross the gut barrier and promote systemic inflammation–were especially represented in female patients with clinically apparent RA. This is an astounding result regarding the inflammatory nature of RA. Larger studies based on complementary sequencing studies could specify the role of the gut microbiota in RA and determine whether dysbiosis is a cause or a consequence of the disease.

Young children have always had to adapt to the diversity and abundance of their environmental microbiome. But with urbanization, our homes have lost some of this abundance and diversity, and the frequency of asthma (and allergies) has simultaneously increased. Many scientists assume there is a link between these two phenomena and are trying to document it and understand underlying mechanisms. An international research team recently made progress on this matter.

Mirror of the environment

First step: analysis of the microbiota (population of microorganisms) present in the dust collected in farms on the one hand, and other homes on the other hand, as part of two studies conducted with cohorts of 2-month old Finnish children (for whom asthma was diagnosed in the first 6 years of life). Important composition differences were observed: dust from farm homes had strong bacterial diversity and abundance, as well as small amounts of specific bacteria and species of archaea (sidenote: archaea Archaea are small microorganisms with the same morphology as bacteria but with a different genetic composition )  typically associated to the rumen (sidenote: rumen First compartment of the stomach of ruminants )  of cattle. The indoor microbiota of non-farm homes contained significant proportions of bacteria associated to humans. Finally, the abundance of fungi varied depending on homes, although not significantly..

Protective diversity

These differences in composition were linked to the development of asthma in the first six years of life. Result: in children growing in non-rural environments, the risk of developing asthma decreased as the microbial composition of indoor dust got closer to that of farms. This pattern was later confirmed in German children living in rural areas. Although the “protective farm effect” is still unclear, the pool of data collected confirms the hypothesis that the presence of specific bacteria and archaea in the indoor environment, and especially in the dust, can protect against asthma. This is good news for the development of a new type of preventive strategies.

Prevalence of food allergies steadily increases in Western countries. Among possible causes: gut dysbiosis related to new lifestyles (overuse of antibiotics, poor dietary habits, increased rate of cesarean deliveries...). This hypothesis was explored by an American team which focused on anaphylactic reactions in mice colonized by gut microorganisms extracted from children with or without b-lactoglobulin allergy.

Allergenic fecal transplant

Fecal samples from 4 allergic newborns and 4 healthy newborns were administered to groups of axenic mice (germ-free mice), before exposing them to b-lactoglobulin. Result: “allergic” animals presented a sharp body temperature decrease and a significantly higher production of IgE and Ig1 anti-b-lactoglobulin antibodies and murine mast cell protease compared to “healthy” mice. However, mice who received a transplant from non-allergic children had no anaphylactic reaction and few temperature variations, thus suggesting the gut microbiota is involved in the mechanisms at play.

Protective vs. non-protective bacteria

Analyses carried out on the donors and on mice have shown notable variations of 58 OTUs (sidenote: Operational Taxonomic Unit groups of organisms usually not cultivated or not identified, classified on the basis of the similarity of the DNA sequencing of a given gene. Frequently used as an equivalent to the concept of species ) based on sensitivity to b-lactoglobulin allergens. 34 of them, from the Lachnospiraceae family, are qualified as “protective” (more abundant in healthy donors) and 24 as “non protective” (more abundant in allergic donors). Their relative abundance, expressed as a ratio, could be used to distinguish between allergic and non-allergic individuals.

Anaerostipes caccae: the ideal ileal bacteria?

Since tolerance to food allergens begins with absorption in small intestine, the team then characterized local bacterial populations and their potential action on the anaphylactic response. A beneficial species was thus identified in the ileum, where microorganisms of the small intestine are most abundant: Anaerostipes caccae (from the Lachnospiraceae family), whose increased content could be synonym of a better protection. This bacterium uses lactate and acetate and produces butyrate, three metabolites involved in the modulation of immune responses in the gastrointestinal tract. All these results highlight the role of commensal bacteria in food allergic reactions and open the way to the development of preventive and therapeutic strategies based on the modulation of the gut microbiota.

Based on recent works, it seems that marathon runners should not be the only ones to step onto the podium: their gut bacteria are also involved in their athletic performance.

The bacterium that turns mice into champions

A team of researchers observed that the postmarathon gut microbiota of runners was particularly rich in bacteria from the Veillonella genus and they isolated in their stool a specific species called Veillonella atypica. The simple inoculation of this bacterium to mice transforms them into seasoned athletes: the little rodents run longer on treadmills!

Marathon runners feed bacteria...

The underlying mechanisms still had to be elucidated. One specificity of Veillonella bacteria gave the researchers an idea: they feed on lactic acid which is produced by the body during extended physical exercise and which causes muscle soreness on the day following a sporting feat. After several additional experiments, the researchers suggested the following model: when they exercise, marathon runners use the sugar (or glucose) stored in their muscles and it is transformed into lactic acid (leading to muscle cramps). A portion of this lactic acid reaches the liver where it will be transformed back into glucose; the rest crosses the intestinal wall and feeds Veillonella bacteria living in their digestive tube.

... and bacteria boost marathon runners

Veillonella, which are well fed by their long-distance runner hosts, rapidly multiply. And that is why the microbiota of runners is so abundant and diverse at the end of a marathon. But it is not the only reason: during physical exercise, bacteria consume lactic acid and transform it in the colon into propionate, a beneficial substance derived from lactic acid which returns into the muscles of athletes via the blood flow and improves their performance. Moreover, in mice, the injection of propionate in the colon was enough to turn them into the kings of treadmill. This win-win relationship between the bacterium and its host allows the athlete to complete its marathon in a record time... their belly full of Veillonella!