What do we already know about this subject?

Polychemotherapy, either with 5-fluorouracil (5-FU), irinotecan and oxaliplatin in combination with folinic acid (FOLFIRINOX), or with gemcitabine and nabpaclitaxel (GnP), is considered the standard of care for patients suffering from metastatic PDAC (mPDAC). However, less than half of all patients are responsive to the therapy, and patients who do not respond (NR, non-responder patients) suffer pain and die within a few weeks. Genetic alterations in PDAC poorly explain the differences between patients who respond to therapy (R, responder patients) and NR patients, which leaves environmental factors, including the intestinal microbiota, as the potential mediators of chemotherapy efficacy. Thus, there is an urgent need to identify environmental factors that might explain the differences between R and NR patients to develop new concepts for future therapies. The intestinal microbiota has been shown to induce a response to immunotherapy in patients with melanoma, and can be modulated by the diet ^{2, 3} . In rare long-term survivor patients with localised PDAC, bacteria can pass from the intestine to the tumour and thus control anti-tumour immune activation. However, most patients suffering from aggressive immunotherapy-resistant mPDAC are treated with polychemotherapy, and it is presently unclear whether and how the microbiota or dietary habits affect the efficacy ⁴ .

What are the main insights from this study?

Analysing the microbiota of 30 mPDAC patients revealed differences between R and NR patients. Transferring the microbiota of R patients to mice with pancreatic tumours reduced the size of the tumours after chemotherapy. The tryptophan metabolite 3-IAA was enriched in R patients and mice with R microbiota, potentially contributing to the response to chemotherapy. The administration of 3-IAA increased the efficacy of chemotherapy in mice (figure 1). The analysis of immune cells in mice showed an increase in CD8+ T cells and a reduction in neutrophils in mice with a microbiota associated with a good response to chemotherapy. 3-IAA affected the MPO of neutrophils, thereby reducing their survival. The combination of 3-IAA and chemotherapy reduced the number of neutrophils and inhibited tumour growth, with MPO playing a crucial role. It is suggested that MPO induces the ROS production leading to cell death during chemotherapy. In-vitro experiments have shown that 3-IAA increases ROS levels. This effect was confirmed in vivo and the inhibition of ROS by N-acetylcysteine abolished the efficacy of FIRINOX in mice with high 3-IAA levels. The authors then showed that the effect of 3-IAA was linked to downregulation of autophagy. Finally, high serum concentrations of 3-IAA were correlated to a reduction in neutrophil counts and improved survival in the two cohorts of human patients.

What are the consequences in practice?

The intestinal microbiota has an effect on chemotherapy responses. The mechanisms involved in this study demonstrates the role of microbial metabolites, particularly tryptophan metabolites. Among these, 3-IAA is not only a predictive marker of response to chemotherapy in PDAC, but could also offer an adjuvant therapeutic drug.

Antibiotic resistance in the environment: A pre-existing challenge

Antibiotic resistance (AR) is an ancient and prevalent phenomenon in the environment existing long before the introduction of antibiotic molecules as therapeutic. The environment serves as a vast reservoir of antibiotic resistance genes with diverse microbial communities harboring resistance mechanisms. AR has been found in various environmental settings, including soil, water, plants, animals, and even in 30,000 years old Arctic permafrost ^{1, 2} . The ecological role of antibiotic molecules and associated resistance in non-clinical settings remains unclear but highlights the fact that a readily available pool of genes predates clinical antibiotic usage and explain rapid emergence in pathogens. The current antibiotic crisis is an evolutionary phenomenon and mitigation strategies needs to account for microbial ecology. It is the rapid acquisition of resistance by pathogens that were previously sensitive leading to therapy failures that is problematic, especially when very few novel antimicrobials are expected to reach the market ³ .

Mechanisms driving the emergence and dissemination of the resistome

The resistome refers to the complete set of genes that encode for antibiotic resistance (AR)-related proteins or those proteins that could potentially evolve into powerful AR agents ⁴ (figure 1). This includes recognized AR genes in pathogenic bacteria (the problematic ones), AR genes from antibiotic-producing organisms, such as Streptomyces spp. producing streptomycin antibiotic and associated resistance gene[5], cryptic AR genes (i.e., genes that could provide resistance in a different genetic setting; e.g., upregulated efflux pumps or downregulated porins), and precursor AR genes that code proteins with a minimal level of affinity or resistance to antibiotic compounds.

The notion of resistome is distinct from “functional and clinically relevant AR” important. Indeed, resistome genes can transition between the different states described above by horizontal gene transfer (HGT), point mutations, or recombination which are leading to new hosts or genetic context where clinically relevant AR phenotype can be expressed. A resistance gene is therefore not problematic per se as this is host and genetic context dependent, but all resistome genes are potential threat with different associated public health risk outcomes. The discovery of a resistance gene towards a clinically relevant molecule, located on a mobile element and hosted by a human pathogen is a critical risk but the same gene, or close homologues, found in a non-pathogenic soil bacterium and not associated with mobile genetic element is a very low risk ARG. Ranking risk of antibiotic resistance in resistome studies is therefore of paramount.

Horizontal gene transfer (HGT) is a key mechanism responsible for the rapid spread of AR genes among bacteria, even across distant lineages. For example, Bacteroides spp., a predominant group in the human gut microbiota, possess macrolide resistance gene ermB identical to those found in several Clostridium perfringens, Streptococcus pneumoniae and Enterococcus faecalis isolates from various geographical origin, indicating genetic connection between Bacteroides and some Gram-positive bacteria that are not prevalent in the human gut ⁶ . Genetic elements, such as plasmids, facilitate the transfer of resistance genes between different microbial species ⁷ . HGT enables the dissemination of genes across diverse environments and bacterial populations, contributing to the overall prevalence and diversity of AR. Co-selection is another significant factor in the spread of AR. The use of non-antibiotic compounds, such as heavy metals and biocides, can co-select for AR genes by exerting selective pressures on microbial populations, either by co-resistance (different resistance determinants present on the same genetic element) and cross-resistance (the same genetic determinant responsible for resistance to antibiotics and metals) ⁸ . Exposure to naturally occurring antimicrobial compounds such as those produced by competing microorganisms or any co-selective compounds can drive the selection of resistant strains ⁹ . The presence of antibiotics in the environment, either from natural sources or human activities, further contributes to the selection pressure for resistance. Additionally, the use of antibiotics in agriculture and veterinary practices can lead to the contamination of the environment, promoting the emergence and spread of antibiotic environmental resistance genes overtime ¹⁰ .

Dysbiosis and the gut resistome in infants: A delicate balance

The environmental reservoir diversity of AR genes and its potential to be transfered poses a threat to the early life human gut microbiome. Strategies such as improved wastewater treatment, responsible use of antibiotics in agriculture and veterinary medicine, and reducing environmental contamination with antibiotic residues and antibiotic resistant bacteria can help mitigate the spread of resistance ¹¹ . Additionally, monitoring and surveillance of environmental reservoirs can provide valuable insights into the emergence and persistence of AR and inform public health interventions.

Our gut is rapidly colonized after birth by microorganisms acquired from their mothers and their surrounding environment. It is during the first years of life that changes are drastic and characterized by a low resilience compared to the more stable healthy adult’s gut microbiome. Newborns and infants are therefore more prone to disruptions in microbial communities, known as dysbiosis. During that period, many factors can influence and perturbate gut maturation and potentially lead to long-term consequence on health ¹² . Mice studies showed that during this critical developmental window, rather than a direct effect of antibiotic molecules, it is the alteration of the gut microbiota composition that is triggering metabolic consequences, such as obesity ¹³ .

Unraveling the antibiotic resistome in infants gut: Insights from a large cohort study

While antibiotic resistance is problematic at all age of life, the establishment of the gut microbiome at early age represent a window of opportunity to limit the buildup of an AR genes reservoir in the gut. It is important therefore to identify the various factors increasing or reducing the abundance of AR genes that could spread to infectious pathogens and cause antibiotic therapy failure throughout life. To study the global human gut resistome researchers rely on holistic approaches interrogating both species presence and genomes functional potential, including the antibiotic resistome. Researchers rely on environmental DNA extraction from proxy samples (e.g., stool samples for the gut) followed by untargeted high-throughput sequencing (shotgun metagenomics). Approximately 80% of human gut bacterial species detected by molecular tools are unculturable, especially the specialized anaerobes inhabiting the gut. It is likely that many microorganisms are organized in multi-species cell aggregates with metabolic co-dependencies making pure strain isolation delicate if not impossible. Using computational methods, it is however possible to reconstruct quasi-complete genomes from metagenomes and associate encoded genes with specific species or even strains of bacteria. In a recent study, researchers analyzed fecal samples from 662 infants from a cohort which followed children from birth to age 7 ¹⁴ . The objectives of the study were to establish a cohort scale overview of the resistome at 1 year of age and identify perinatal and environmental factors associated with ARG abundance and diversity. The researchers used shotgun metagenomic sequencing of samples obtained at 1 year of age from the 662 children to identify ARGs and bacterial taxa present in the samples (figure 2). Making use of their large dataset, the authors were able to reconstruct Metagenomes Associated Genomes (MAGs), allowing them to confidently annotate the taxonomy of recovered genomes and their AR genes content.

A first result observed was that all children had at least one type of multiple drug ARG in their gut, indicating that even in absence of antibiotic treatment, there is a resident resistome associated with the gut microbiome. Indeed, many multidrug resistance genes were identified as efflux-pumps. These proteins are normal component of every bacterial cell but some can confer AR and are very easily co-selected by cross-resistance, for example towards heavy metals or biocides, potentially explaining their high abundance in the gut, but also in all environments ^{8, 15} . Another striking result was the clear separation of the cohort in two groups based on their resistome profile. The first group was characterized by a higher ARGs diversity and relative abundance with Escherichia coli as the main contributor of ARGs, as shown in (figure 2). This agrees with previous observations that Enterobacteriaceae are abundant early in life but should decrease rapidly when Bacteroidetes population starts colonizing the gut. Alteration of this maturation in some children can be associated to a combination of several factors, such as antibiotic usage, mode of delivery, rural or urban household that seems to delay the reduction of the population of Escherichia coli and lead to an increased resistome at 1 year of age. This is also confirmed by the observation that the higher abundance of ARGs is associated with a lower gut microbiome maturity score, based on ratios of specific age-related taxa ¹⁶ .

This indicates some level of resilience at an early age which could be potentially improved with targeted intervention, e.g., with pro- or prebiotics, and remains to be tested. At the cohort scale, the largest differences in ARG abundance were however found for resistance genes towards antibiotic that were not prescribed to the children, underlying that perinatal and environmental factors besides antibiotic therapy are also driving the gut resistome. Another observation from that study that connects the surrounding environment, and associated resistome, and the gut resistome was that children whose households was in urban areas had a significantly higher load of ARGs than children living in rural areas. There is a myriad of potential confounding factors that could explain this but it strengthens the fact that the environment contribution to the development of the early life microbiome is extremely important.

It can be hypothesized that urban living is associated with less contact with the outdoor and a decreased microbiome diversity, or that the type of lodging found in rural (house) or urban (appartement) environment are associated have consequences on the indoor microbiome as seen in bed dust.

Alzheimer’s disease is progressive and silent. During the so-called pre-clinical phase, cognitive state appears normal. However, in-depth tests have already shown the progressive accumulation of two proteins in the brain, β-amyloid (Aβ) and tau proteins, which cause brain damage and a slow degeneration of neurons, beginning in the memory center and then spreading to the rest of the brain.

After this silent phase, the first symptoms of dementia (sidenote: Dementia Brain disorders that affect memory, thinking, behavior, and emotions. Changes in mood and behavior sometimes precede memory problems. Symptoms worsen over time. Most sufferers eventually require assistance in their day-to-day life. Sources: OMS and Alzheimer’s Disease International ) appear. This is the clinical stage of Alzheimer’s disease, marked by mood and personality changes, memory lapses, forgetting certain words to the point of being difficult to understand, disorientation in space and time, leaving things in inappropriate places (keys in the fridge), etc.

Gut dysbiosis in pre-clinical Alzheimer’s disease

What role does the gut microbiota play in all this? We already know that in the clinical stage of the disease, patients have an unbalanced gut microbiota. According to a US study published in 2023, this imbalance also exists in the pre-clinical stage and is all the more pronounced the more β-amyloid proteins have accumulated. This imbalance in the gut microbial ecosystem (or dysbiosis) is not linked to diet: future Alzheimer’s patients who do not yet show any signs of dementia have a diet comparable to that of healthy patients who are not slowly succumbing to the disease.

Can this help predict the subsequent clinical form of the disease?

The team identified gut bacteria that are generally over- or under-represented in the pre-clinical stage. These bacteria allowed them to use machine learning (sidenote: Machine Learning Automatic learning whereby artificial intelligence solves a task based on metagenomic and metabolomic data collected, in this case the identification of discriminating bacterial species. Wazid M, Das AK, Chamola V, et al. Uniting cyber security and machine learning: Advantages, challenges and future research. ICT Express, 2022; 8(3), 313-321. ) to improve their predictive models for Alzheimer’s disease. Admittedly, the gain is small when the initial model incorporates β-amyloid proteins, which are the main pre-clinical signature of Alzheimer’s disease. However, the latter requires lumbar punctures and brain neuroimaging, complex and uncommon procedures. When models are based solely on readily available data (age, sex, hypertension, family history, etc.), the addition of bacterial data from a stool sample improves model sensitivity (sidenote: Sensitivity The sensitivity of a medical test measures its ability to correctly detect those suffering from a disease (identification of as many sufferers as possible). A sensitivity of close to 100% means the test has little chance of missing cases of a disease, i.e. few false negatives (few undetected true sufferers). Bertrand D, Fluss J, Billard C. Efficacité, sensibilité, spécificité : comparaison de différents tests de lecture. L’Année psychologique, 2010 ; 110, 299-320. ) by 6.8% and specificity (sidenote: Specificity Specificity is the probability that the test will be negative knowing that the subject is healthy. It therefore measures a test’s ability to detect healthy individuals. The closer the specificity is to 1, the fewer the false positives. Bertrand D, Fluss J, Billard C. Efficacité, sensibilité, spécificité : comparaison de différents tests de lecture. L’Année psychologique, 2010 ; 110, 299-320. ) by 27.1%.

This makes it easier to pre-identify at-risk patients, who can then be prescribed more in-depth examinations. If bacteria are indeed the cause of these changes, which has yet to be confirmed, these results also suggest the possibility of modifying the gut microbiota to limit the progression of Alzheimer’s disease.

Previous studies have highlighted dysbiosis in the gut microbiota of patients showing symptoms of Alzheimer’s disease. But what about before the first symptoms appear? A team from the University of Washington School of Medicine in the US examined this question by analyzing the microbiota of 164 people aged between 68 and 94 who had no cognitive impairment, but 49 of whom showed biomarkers for the pre-clinical stage of Alzheimer’s disease (sidenote: Biomarkers Pathogenic β-amyloid (Aβ) and tau proteins measured via positron emission tomography (PET) or by levels in cerebrospinal fluid (CSF), markers of neurodegeneration (temporo-parietal hypometabolism, hippocampal atrophy, etc.) identified via CSF and magnetic resonance imaging (MRI). ) . The results were unequivocal: the gut microbial taxonomic profiles of the 49 “pre-patients” differed from those of the 115 controls.

^{Sources (sidenote: OMS https://www.who.int/fr/news-room/fact-sheets/detail/dementia )}

A gut microbiota specific to pre-clinical stages

This dysbiosis correlates with markers of pre-clinical stages of the disease, notably the deposition of β-amyloid plaques in the brain. However, it is not linked to biomarkers of neurodegeneration (temporo-parietal hypometabolism, hippocampal atrophy, etc.). Thus, the gut microbiota seems to change from a very early, asymptomatic stage of the disease.

More specifically, the content of certain bacteria either increases or decreases, including Dorea formicigenerans, which has pro-inflammatory properties, Oscillibacter sp. 57_2, which may be associated with reduced epithelial integrity, anti-inflammatory Faecalibacterium prausnitzii, and to a lesser extent, Coprococcus catus, Anaerostipes hadrus, Methanosphaera stadtmanae, and Ruminococcus lactaris. Some of these gut bacteria may therefore be involved in the causal chain, although further experiments are required to confirm any such causal link and rule out a simple co-occurrence.

Simplifying and improving identification of at-risk patients

In any case, this bacterial signature may help improve disease prediction. This is based on a test carried out on a sub-group of 65 patients, where the addition of these bacterial taxa improved the accuracy of predictive models. This improvement is slight (sensitivity +1.5%, specificity +5.0%) when the initial model includes the β-amyloid protein, the main pre-clinical signature of the disease. However, the latter requires complex tests. When models are based solely on readily available data (demographics, clinical covariates, and genetics), the addition of taxonomic characteristics, which require only a stool sample, improves sensitivity by 6.8% and specificity by 27.1%. This makes it easier to pre-identify at-risk patients, who can then be prescribed more in-depth examinations (lumbar puncture and neuroimaging). Lastly, the study could open the door to interventions on the microbiota aimed at limiting the progression of Alzheimer’s disease towards clinical stages.

Observational studies have one drawback: they cannot distinguish the chicken from the egg, and when it comes to microbiota, they cannot show whether dysbiosis is the cause or consequence of an illness. The solution? Mendelian randomization, named after the famous Austrian botanist Gregor Mendel, who laid the foundations of genetics with a few pea plants.

Mendelian randomization

Mendelian randomization is a statistical and genetic approach used in epidemiological research to assess cause-and-effect relationships between an exposure (e.g. a risk factor) and an outcome (e.g. a disease). It is based on the natural genetic variations in people, inherited at random from their parents. Use of this method can make it possible to establish (or refute) a causal link between an exposure (e.g. gut microbiota) and the genetic variants associated with a disease — ischemic stroke (or cerebrovascular accident) — and, more precisely, 3 subtypes: large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES), based on data from the European Megastroke (sidenote: European Megastroke Consortium: 40,585 stroke cases (including 4,373 LAS, 5,386 SVS and 7,193 CES) and 406,111 controls of European origin.   ) Consortium ².

Identification of a handful of gut bacteria

To do this, the Chinese team carried out a Mendelian randomization analysis based on 194 bacterial traits of the European participants in the MiBioGen ³ consortium (18,340 individuals from 24 population cohorts). 

The results from these cohorts show that gut microbiota is not linked to ischemic stroke subtypes. However:

• 4 bacteria increase the risk of LAS and 5 reduce it;
• 3 bacteria raise the risk of SVS and 6 decrease it;
• 4 bacteria amplify the risk of CES and 5 restrict it.

These results suggest a causal effect of the abundance of certain bacteria on the risk of stroke subtypes. In particular, Intestinimonas protects against the risk of LAS and SVS, and the Lachnospiraceae NK4A136 group against SVS and CES. According to the authors, these 2 bacteria could potentially be probiotics capable of mitigating the risk of ischemic stroke through metabolic regulation, if longitudinal studies and clinical trials go on to support their findings.

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The use of any medicinal products is highly regulated and requires marketing authorization. However, in very rare cases, it is possible to benefit from a last-chance waiver known as "compassionate access". This allows medicinal products to be used without marketing authorization to treat serious or rare diseases for which there is no cure whereas time is running out. A young 30-year-old mother who had suffered a series of pregnancy losses since the birth of her first child, some of them very late (up to 6 months into the pregnancy), was able to obtain a vaginal microbiota transplant after having obtained such access. In other words, healthy microbiota from a female donor was deposited in her vagina in September 2021.

Use of VMT to treat vaginal dysbiosis

But why? Because this young mother had a very unbalanced vaginal microbiota, dominated not by beneficial lactobacilli (sidenote: Lactobacilli Rod-shaped bacteria whose main characteristic is the production of lactic acid, from where they get the name “lactic acid bacteria”.  Lactobacilli are present in the oral, vaginal and gut microbiota of humans, but also in plants and animals. They are found in fermented foods, such as dairy products (e.g. certain cheeses and yoghurts), pickles, sauerkraut, etc. Lactobacilli are also found in probiotics, with certain species recognized for their beneficial properties.   W. H. Holzapfel et B. J. Wood, The Genera of Lactic Acid Bacteria, 2, Springer-Verlag, 1st ed. 1995 (2012), 411 p. « The genus Lactobacillus par W. P. Hammes, R. F. Vogel Tannock GW. A special fondness for lactobacilli. Appl Environ Microbiol. 2004 Jun;70(6):3189-94. Smith TJ, Rigassio-Radler D, Denmark R, et al. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr. 2013 Jun;109(11):1999-2007. ) , as is the case in a healthy vagina, but by the dreaded Gardnerella spp. bacteria, which explains her nine years of itching and abundant, yellow/green, foul-smelling vaginal discharge, which worsened during her attempts to become pregnant and resisted all attempts at treatment...

 A pregnancy carried to term

The graft seems to have taken hold very quickly. The dysbiosis and its symptoms disappeared and lactobacilli similar to those of the donor largely colonized the recipient's vagina. In February 2022, the patient became pregnant naturally and the lactobacilli were still living peacefully in her vagina. The only fly in the ointment was the return of Gardnerella spp. in the sixth week of pregnancy. This did not worry the researchers as a second vaginal microbiota transplant was initially planned for two weeks later. However, this transplant was ultimately canceled as the lactobacilli had regained the upper hand on the day of the procedure. And as all's well that ends well, a full-term perfectly healthy baby boy was born via planned cesarean section.

It is nevertheless important not to jump to conclusions or to believe that vaginal microbiota transplantation represents a miracle cure for female infertility. This was just one case, and the patient had another illness that causes miscarriages and whose treatment could explain, in part or in whole, the success of this pregnancy. Put another way, while we shouldn't disregard the results of this case study, we shouldn't get too carried away either.

Endometriosis affects 10% to 15% of women of childbearing age, resulting in chronic pain, hypofertility, and even infertility. Several hypotheses about what causes the disease have been put forward, most notably retrograde menstruation. However, other mechanisms have not been ruled out.  According to the work of a Japanese team, the microbiota of the uterine cavity may be involved, in particular the bacterial genus Fusobacterium, a pro-inflammatory opportunistic pathogen.

Fusobacterium: the cause of an inflammatory response?

Analyses of tissues collected during hysterectomy from 79 patients suffering from endometriosis revealed a greater presence of bacteria from the genus Fusobacterium in the uterine endometrium and ovarian fibroblasts compared with 76 controls not suffering from endometriosis (samples taken during surgery for cervical dysplasia, adenomyosis, etc.). Fusobacterium was present in the endometrium of 64.3% of patients with endometriosis, compared with 7.1% for healthy controls.

In addition, vaginal samples showed an increased abundance of this bacterium in the vaginal area of women suffering from endometriosis. This supports the existing hypothesis that the vaginal microbiota plays a role in the pathogenesis of the disease, bearing in mind that the digestive microbiota also appears to be involved.

Vaginal inoculation of bacteria

Moreover, vaginal inoculation of Fusobacterium in a mouse model of endometriosis resulted in a marked increase in fibroblasts and an increase in the number and weight of lesions, in contrast to inoculation with other bacteria, such as Lactobacillus iners or Escherichia coli. 

Further studies have led the authors to propose the following scenario: infection of endometrial cells by Fusobacterium leads to the production of the growth factor TGF-β1 by macrophages, which in turn induces the transition of fibroblasts from a quiescent state to an activated state in which they express a cytoplasmic protein called transgelin (TAGLN), which then promotes the proliferation, migration, and adhesion of these fibroblasts outside the endometrium. This mechanism appears to be validated in humans: TAGLN is also over-expressed in patients’ fibroblasts, promoting their proliferation and motility.

An antibiotic treatment?

Lastly, the researchers tested a broad-spectrum vaginal antibiotic treatment (metronidazole and chloramphenicol) on animals over 21 days with the aim of eradicating F. nucleatum. Administered when the mice were inoculated with Fusobacterium or subsequently (when the lesions had grown), the treatment limited F. nucleatum, TGF-β1 and TAGLN expression and reduced the number and weight of lesions. Hope for a future approach to treating endometriosis? A clinical trial underway in 2023 aims to reveal what impact antibiotics have on women suffering from endometriosis. The results may one day make it possible to prescribe antibiotics to patients with endometriosis who are infected with Fusobacterium.

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A significant new hope has arisen for all women suffering from endometriosis (sidenote: Endometriosis Endometriosis is a chronic gynecological disease linked to the presence of tissue similar to the uterine mucosa outside the uterine cavity, particularly in the peritoneum and ovaries. ) : a bacterium of the Fusobacterium (sidenote: Fusobacterium Fusobacterium is a genus of filamentous bacteria that lives in the mouth (dental plaque), digestive system, vagina and, to a lesser extent, the uterine cavity. This pathogenic bacterium is implicated in periodontitis (inflammation at the base of the tooth) and colorectal cancer. ) genus may be involved, representing a potential target for treatment. In particular, a simple course of antibiotics may be enough to make this pathogenic bacterium retreat, reducing the painful lesions.

^{Sources (sidenote: 1. Kvaskoff M. Epidémiologie de l’endométriose. In : Petit E, Lhuillery D, Loriau J, Sauvanet E. Endométriose : Diagnostic et prise en charge. Issy-les-Moulineaux : Elsevier Masson ; 2020. P.9-14.    2. https://www.biocodexmicrobiotainstitute.com/en/international-microbiota-observatory-focus-women-health )}

Bacterial effect countered by an antibiotic

Japanese researchers from Nagoya University ²  have shown that, in laboratory mice used as a model, vaginal inoculation with bacteria from the genus Fusobacterium induced lesions typical of endometriosis, which were more numerous and more severe than in control mice.  This suggests that Fusobacterium is involved in the genesis of the disease; but it also leads to possible solutions. Indeed, antibiotic treatment targeting Fusobacterium reduced the number and weight of lesions in the mice. This discovery raises the hope that this antibiotic treatment may also be effective in women.

Analysis of the mechanisms at play

But that’s not all. The Japanese team carried out numerous experiments to try and understand the mechanisms involved. This meticulous work led to the following hypothesis: the presence of Fusobacteria in the uterus activates the women’s immune system, provoking a cascade of reactions that leads to the production of a protein called transgelin, which in turn promotes the development of endometriosis.

Clinical study underway

The involvement of the microbiota in endometriosis has been suspected for some time. For example, analyses of the vaginal flora have been used to predict the severity of the disease, while 90% of women affected by endometriosis also have associated digestive disorders (irritable bowel syndrome in particular). Nevertheless, these new results were sufficiently promising for the Department of Obstetrics and Gynecology at Nagoya University Hospital to launch a clinical study in 2023 ³ into the use of an antibiotic.

Pending the results, please do not take antibiotics without a prescription or medical advice. If used incorrectly, you may reduce their effectiveness for when you really need them.