Synopsis of the course

This accredited course aims to educate gynecologists, midwives, and pharmacists on the significance of microbiota, particularly vaginal microbiota, for intimate health. Led by a renowned expert, Dr. Graziottin, thoroughout the course participants will gain a comprehensive understanding of how microbiota impacts intimate health across the lifespan. We will first cover the basic insights about the gut microbiome before delving into the vaginal microbiota throughout different life stages, including the potential for a sterile placenta, neonatal microbiota, and changes during infancy, puberty, fertile years, and menopause. Do not miss the practical recommendations, common misconceptions and summarizing key takeaways that will provide you with the necessary knowledge and skills in your clinical practice.

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This activity is supported by unrestricted financial support from Biocodex.

Who is Alessandra Graziottin?

Alessandra Graziottin, MD is an Italian gynecologist, oncologist, sexologist, and psychotherapist. She is the director of the Center for Gynecology and Medical Sexology at the San Raffaele Resnati Hospital in Milan.

• In 2008 she founded the Alessandra Graziottin Foundation for the treatment of pain in women Onlus, of which she is president.
• She is currently Consultant Professor at the Advanced Master in Andrology and Sexual Medicine of the University of Firenze.
• She also was Consultant Professor at the Advanced master's in clinical Sexology of the University of Pisa, and Professor at the Master Course of Sexual Medicine for Students of Psychology of the University of Venezia and Salesian University (UPS) of Roma.

She is a renowned gynecologist, having published 22 scientific books and 7 popular books (as the author, co-author, or editor), over 90 chapters of scientific books, 8 educational manuals for women, and more than 400 scientific articles on various aspects of gynecology and medical sexology.

Conflicts of Interest Statement: The author declares receiving honoraria from stellas, Fagron, Mammowave, Mylan, Named, Techdow, Uriach; participating as speaker in bureaus sponsored by Astellas, Biofemme, Bromatech, Lolipharma, Named, Techdow, Uriach; and being part of advisory boards of Astellas, Mylan, Techdow, Uriach.

What is Xpeer?

Xpeer Medical Education is the first accredited medical education app in the market, with video microlearning engaging videos of just 5 minutes.

With a powerful algorithm to personalize the user experience and the contents as the most popular entertaining streaming platforms, it offers a brand new experience for the continuing education and professional development of the healthcare professionals.

Accredited by the European Union of Medical Specialists, it delivers high quality scientific medical education pieces. On Xpeer, you will find this curriculum on Microbiota and 500 hours of medical education in 2021 in your specialty, technologies and professional and personal skills.

Information on accreditation

The app Xpeer is accredited by the European Accreditation Council for Continuing Medical Education (EACCME) to provide official ECMEC credits recognized officially in 26 countries.

The credits for the users of the module will be 1 European CME credit (ECMEC®) for every hour (60 minutes of actual e-learning excluding introductions etc.) of use, provided that the users have completed a module and have passed the relevant assessment.

Over 80% of urinary tract infections are caused by uropathogenic Escherichia coli (sidenote: Uropathogenic Escherichia coli E. coli that often have additional genes (compared with commensal E. coli) which boost their virulence (flagella, toxins, surface polysaccharides, etc.). ) . These gut bacteria can migrate from the anus, colonize the urethra and then migrate up into the bladder. In fact, previous studies have shown that women suffering from urinary tract infections have an increased abundance of E. coli in their digestive system, with similarities between the gut species and those colonizing the urinary tract. 

To assess dysbiosis and other potential risk factors in women with a history of cystitis, researchers enrolled 753 female volunteers aged 18 to 45 who had been diagnosed with a UTI in the last five years and were otherwise in good health. ¹

Opt for a healthier diet

Nearly ¾ of the women studied (71%) had gut dysbiosis, which proved to be associated not only with the recurrence (sidenote: Recurrent urinary tract infection A recurrent urinary tract infection is defined as the occurrence of ⩾2 symptomatic episodes in 6 months or ⩾3 symptomatic episodes in 12 months. ) of their urinary tract infections, but also with the presence of antibiotic multidrug resistance in their flora.

Another particularity of the population studied is their diet, whether it be drinks (less than 1 L of water per day, consumption of sugary drinks), food (over-representation of salty products, high-calorie diets rich in added sugars and saturated fats), or dietary supplements intended to prevent urinary tract infections.

For the researchers, these observations support the link between diet and the composition of the gut microbiota. In this regard, they refer to previous studies which have shown that only 12% of structural variation in the gut microbiota can be attributed to genetic changes, while 57% can be explained by dietary changes.

Microbiota as a new therapeutic strategy 

Although the standard treatment for urinary tract infections is antibiotics, in the long term they disrupt the gut microbiota (dysbiosis) and encourage multidrug resistant organisms. Hence the importance, according to the authors, of alternative and complementary therapeutic choices.

The researchers also point out the beneficial effects of probiotics, in particular Lactobacillus spp. which reduces the adherence, growth and colonization of uropathogenic bacteria such as E. coli: Enteric-release L. salivarius travels to and protects the urinary and vaginal microbiota, and a probiotic composed of two strains of Lactobacillus and cranberry extracts significantly reduces the number of recurrent urinary tract infections in young premenopausal women, compared with a placebo product.

Probiotics also have a major advantage over antibiotics: the administration of lactobacilli does not encourage the development of resistance.

The regulation of appetite is a complex, multi-dimensional process that plays a pivotal role in maintaining energy homeostasis. Satiety, distinct from hunger and satiation, is central to this regulation. 

• Hunger represents the physiological need for food, typically driven by signals from the brain in response to energy depletion.
• Satiation, on the other hand, marks the sensation of fullness experienced during a meal, signalling an end to eating.
• In contrast, satiety refers to the prolonged sense of fullness that suppresses further eating between meals, thus influencing the timing of subsequent food intake.

Understanding the mechanisms behind satiety is critical for healthcare professionals and individuals alike striving to combat obesity, diabetes, and other metabolic disorders. Increasingly, research points to the gut microbiota as a key regulator of satiety signalling, linking the microbial environment of the gut to brain function via what is commonly termed the gut-brain axis. Emerging evidence suggests that gut bacteria and their metabolites, particularly short-chain fatty acids (SCFAs (sidenote: SCFAs Short Chain Fatty Acids are a source of energy (fuel) for the cells of the individual. They interact with the immune system and are involved in the communication between the intestine and the brain. Sources:
Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) ), are integral to satiety regulation, influencing the release of satiety hormones and modulating appetite. ^1,2,3

We invite you in this article to explores the growing body of evidence on the gut microbiota’s role in regulating satiety, focusing on microbial metabolites, their interaction with the gut-brain axis, and the implications for clinical practice. We will analyse how dietary interventions aimed at modifying gut microbiota composition, such as the use of probiotic, prebiotics and fiber-rich diets, can influence satiety and offer novel approaches for managing obesity and related metabolic conditions.

Gut-brain conversations: how the microbiota shapes satiety signals?

The gut-brain axis is an intricate network that communicates satiety signals between the gut and brain. This interaction is largely influenced by the gut microbiota, which regulates appetite through hormones like glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK). These hormones are produced by specialized cells in the gut called enteroendocrine cells (EECs) in response to food intake.

Together, these hormones act on the brain to reduce food intake and prolong the feeling of fullness, helping to maintain a healthy balance in food consumption.

One of the microbiota’s key contributions is the production of SCFAs - acetate, propionate, and butyrate - during fiber fermentation. SCFAs stimulate the release of GLP-1 and PYY, reinforcing fullness and helping control appetite. ¹ Additionally, SCFAs interact with the vagus nerve, which directly connects the gut to the brain’s hunger centers, enhancing satiety signals. ²

The microbiota’s role extends beyond signaling; SCFAs also reduce inflammation in the hypothalamus, preserving the integrity of satiety regulation and helping prevent obesity-related metabolic disorders. ² But how do probiotic and specific dietary interventions, such as prebiotics, influence the gut microbiota to enhance satiety?

The role of probiotics in enhancing satiety signals

Recent studies have shown that certain bacteria can produce proteins that send signals to our brain, telling us we’re full. One example is a protein called ClpB, produced by some bacteria like Hafnia alvei. This protein behaves similarly to alpha-MSH, a hormone that helps regulate appetite. This protein stimulates the release of PYY, a hormone that promotes feelings of fullness and reduces appetite. ³

Preclinical studies have shown that Hafnia alvei can help reduce food intake and body weight gain in animal models by amplifying these satiety signals. ³ When used as a probiotic supplement, Hafnia alvei may enhance the feeling of fullness in humans, supporting healthy eating behaviors and contributing to long-term weight management. ⁴ Although more research is needed, early findings suggest that probiotics could offer a complement to dietary interventions aimed at controlling appetite and reducing excess weight. ³

Fueling satiety: how prebiotics and dietary fibers modulate the microbiota?

Dietary interventions, particularly those involving prebiotics and dietary fibers, offer a direct way to influence the gut microbiota and enhance satiety. Prebiotics are non-digestible food components that selectively stimulate the growth and activity of beneficial gut bacteria. A prime example is inulin, a fiber that increases the production of SCFAs, notably propionate and butyrate, which play a key role in satiety signaling. ²

In human studies, inulin-propionate ester (IPE) supplementation has shown promising results. For instance, subjects who consumed IPE experienced a decrease in ad libitum energy intake, meaning they naturally reduced their food consumption without conscious effort. ² The SCFAs produced from fiber fermentation, particularly propionate, directly stimulated the release of GLP-1 and PYY, enhancing feelings of fullness. ¹

Additionally, resistant starch, another fermentable fiber, has demonstrated its ability to reduce postprandial glucose levels and influence satiety hormones. One study showed that resistant starch supplementation over six weeks reduced leptin levels, a hormone involved in long-term energy balance, signaling improved appetite regulation. ¹

These examples highlight how fiber-rich diets can modulate gut microbial activity to positively affect satiety. But what about other microbial metabolites beyond SCFAs? How do they influence the central and peripheral regulation of hunger?

Beyond fiber: the role of neuroactive metabolites in appetite control

In addition to SCFAs, gut bacteria produce several neuroactive metabolites that play crucial roles in regulating appetite and satiety through both central and peripheral pathways. Among these, serotonin, gamma-aminobutyric acid (GABA), and dopamine are key neurotransmitters involved in modulating food intake and energy balance. ²

In the case of GABA, certain strains of Lactobacillus and Bifidobacterium can produce this neurotransmitter. GABA affects the hypothalamus, which is central to hunger regulation, by modulating neural circuits that control feeding behaviour. Studies have shown that germ-free mice exhibit altered GABA signalling, resulting in increased appetite, highlighting the critical role of gut-derived GABA in controlling hunger. ³

Moreover, dopamine, which is involved in food reward mechanisms, is also influenced by the gut microbiota. Imbalances in dopamine pathways can lead to overeating and even binge-eating behaviours, underscoring the microbiota’s potential role in managing not just hunger but food addiction.¹

Dysbiosis: when gut imbalance sabotages satiety

Dysbiosis, the imbalance or maladaptation of the gut microbiota, has emerged as a critical factor in the disruption of normal satiety signals. In individuals with obesity and metabolic disorders, dysbiosis is commonly observed, characterized by a reduction in microbial diversity and an overgrowth of certain pathogenic bacteria. ³ This imbalance can impair the production of key microbial metabolites, particularly SCFAs, which are essential for regulating the hormones responsible for satiety, such as GLP-1 and PYY. ¹

Research shows that individuals with dysbiotic microbiomes often exhibit elevated levels of the appetite-stimulating hormone ghrelin, leading to persistent feelings of hunger and difficulty in maintaining a healthy energy balance. ³ These disruptions highlight the importance of maintaining a healthy, diverse microbiota not only for digestive health but also for proper appetite regulation and long-term metabolic control.

Rewiring satiety: harnessing probiotic, prebiotics and fiber-rich diets for therapeutic gain

The therapeutic potential of probiotics, prebiotics and fiber-rich diets in modulating the gut microbiota offers a powerful tool to enhance satiety and manage metabolic disorders. ⁸ Research consistently shows that dietary fibers, such as inulin, fructooligosaccharides (FOS), and resistant starch, serve as critical agents in stimulating SCFA production - specifically butyrate, propionate, and acetate - which directly influence satiety regulation through the gut-brain axis. ⁹

The evidence points to a future where precision nutrition - tailored dietary interventions based on an individual’s microbiome profile - could be a key therapeutic strategy. ¹⁰ By targeting the microbiota with specific probiotic, prebiotics and fibers, clinicians can restore gut balance, enhance satiety, and help patients manage both appetite and metabolic health more effectively. As the understanding of the microbiota’s role in satiety deepens, it offers a new horizon of personalized therapies that go beyond traditional approaches to treating obesity and metabolic diseases. ¹¹

This is one of the downsides of c-sections: since the baby is not born vaginally, it has no time to taste (literally!) its mother’s vaginal and fecal bacteria. While this “meal” may seem unappetizing at first glance, it is nonetheless essential to the development of the child and its microbiota. Some even believe that the increased incidence of autoimmune diseases, asthma, and obesity in children born by c-section may be due to the fact that, deprived of this royal feast, newborns extracted from their mother’s womb via c-section may not receive all the good bacteria needed for their immune and neurological development. This is a serious concern, considering that one in four children is born by c-section.

Fathers are the solution

Research has therefore been looking for solutions, including the transfer of vaginal flora from mother to child: within two minutes of birth, the child’s mouth, face, and body are swabbed with a gauze previously placed in the maternal vagina. However, the results have not lived up to expectations.

Fortunately, research published in mid-2024 suggests a much easier solution: fathers. In fact, while the mother is the primary provider of gut flora in the child’s first days, the father (and all relatives) also plays a role, and more and more as the months go by.

By the child’s first birthday, the father’s contribution has even become equal to that of the mother. This has a major advantage: whereas maternal bacterial donations depend on the mode of delivery, the father represents a stable source. Another advantage is that paternal and maternal bacteria are distinct, with the two complementary sources building a solid microbiota for the newborn.

Fecal microbiota transfer and probiotics

The team went even further, proposing additional boosts to newborns’ gut flora. Gone are the days of gauze laden with mothers’ vaginal microbiota: a transfer of maternal fecal flora appears to be far more effective in ensuring that a child born by c-section quickly builds up a healthy gut flora, capable of resisting the onslaught of pathogens.

Moreover, nature’s intricate design ensures that the bacteria that take hold are mainly those capable of breaking down the sugars in breast milk. These strains may be developed in future probiotics to boost the flora of very young babies.

In a groundbreaking discovery, researchers have found that certain gut bacteria can convert stress-related hormones into progestins hormones, all with the help of hydrogen gas. This research, led by Megan McCurry and her team ¹ , reveals how gut microbes, specifically Gordonibacter pamelaeae and Eggerthella lenta, metabolize glucocorticoids - hormones produced by the body in response to stress - into progestins, which play crucial roles in pregnancy and brain function. The findings, published in Cell, open new doors for understanding how the gut microbiome influences women’s health, especially during pregnancy.

The unexpected role of hydrogen gas

One of the most surprising discoveries in this study is the role hydrogen gas plays in gut bacterial metabolism. Traditionally seen as a byproduct of digestion, hydrogen gas is now shown to be a key factor that boosts the bacteria's ability to convert glucocorticoids into progestins. The research demonstrates that hydrogen gas production by gut bacteria such as E. coli creates an environment that promotes this steroid transformation. When these bacteria are grown together, they produce significantly more hydrogen, which facilitates the conversion process.

Bacterial progestin production: a potential link to pregnancy and mental health

The research also reveals that the gut bacteria's conversion of stress hormones into progestins has physiological relevance, especially during pregnancy. The study found that levels of bacterial progestins were significantly higher in the feces of pregnant women compared to non-pregnant women. One such progestin, allopregnanolone, is already FDA-approved as a treatment for postpartum depression, hinting at the potential impact of this bacterial process on maternal mental health.

This link between bacterial hormone production and pregnancy is crucial, as progestins not only regulate pregnancy but also act as neurosteroids that affect brain function. The study suggests that these bacterial transformations could influence not just pregnancy outcomes but also postpartum conditions like depression and anxiety.

Gut microbes: the new endocrine players?

Beyond pregnancy, the implications of these findings extend to broader health contexts. If gut bacteria can transform stress hormones into bioactive compounds that affect the brain and reproductive systems, this raises exciting possibilities for how we understand gut health’s impact on overall hormone regulation. The discovery suggests that the gut microbiome acts almost like an additional endocrine organ, capable of influencing hormonal balance and mental health.

Recognizing the microbiome’s role in hormone regulation could pave the way for innovative treatments targeting gut bacteria. In the future, microbial therapies might help manage conditions related to hormone imbalances, such as polycystic ovary syndrome (PCOS), mood disorders, or even fertility issues.

Mosquito-borne flaviviruses such as Zika, Dengue, West Nile virus, and yellow fever are potentially fatal to humans. The cause for concern is greater still given that climate change and phenomena such as El Niño favor such vector-borne diseases (sidenote: Vector-borne disease A disease where a pathogen is transmitted to a host (human or animal) by the bite of a vector, such as mosquitoes, flies, ticks, or fleas. 
Vector-borne diseases account for around 17% of all infectious diseases worldwide, with the WHO estimating that 80% of the world’s population lives at risk from at least one vector-borne disease.
  Explore https://www.pasteur.fr/fr/innovation/toute-actualite/actualites-innovation/comb… ) , while mosquito control and population biological control campaigns have had limited impact to date.

What about adopting an entirely different strategy? Modifying the mosquito’s gut microbiota may protect it from infection and hence prevent it from transmitting the virus to mammals, including humans.

Bacterium that protects both mosquito and human

In this study, Chinese researchers ² isolated 55 bacteria living in the digestive system of female Aedes albopictus mosquitoes, the main vector of Dengue fever, from insects captured in southern Yunnan. These bacteria included Rosenbergiella_YN46 (so named because it was identified in Yunnan), which, inoculated at a dose of 1.6 × 10³ CFU (colony forming units), provided A. albopictus with persistent protection against flaviviruses (sidenote: Flavivirus is a genus of viruses which consists of >70 members including several that are considered significant human pathogens. Transmitted to humans through the bite of infected mosquitoes, Flaviviruses display a broad spectrum of diseases that can be roughly categorised into two phenotypes:
- systemic disease involving haemorrhage (Dengue and yellow Fever virus)
- and neurological complications (West Nile and Zika viruses) Explore https://pubmed.ncbi.nlm.nih.gov/34696709/ ) .

How does this gut bacterium found in flower nectar enable A. albopictus and Aedes aegypti mosquitoes to resist infection by Dengue and Zika? By secreting a glucose dehydrogenase that converts glucose into gluconic acid, rapidly acidifying the mosquito’s intestinal lumen (pH < 6.5 after a blood meal). This acidic environment irreversibly modifies the protein envelope of flavivirus virions, preventing them from entering the mosquito’s gut epithelial cells.

Effective strategy on a large scale?

But the researchers’ work did not stop there. Noting that Dengue prevalence varied between prefectures of Yunnan province, they wanted to see whether this phenomenon went hand in hand with an uneven presence of the bacterium. Indeed it did. Rosenbergiella_YN46 was more prevalent in the digestive system of mosquitoes from Wenshan (91.7%) and Pu’er (52.9%) prefectures, where only a few isolated cases of Dengue have been reported, while the bacterium was rare in mosquitoes from Xishuangbanna (6.7%) and Lincang (0%) prefectures, where Dengue is endemic. 

Complementary experiments under semi-field conditions provide hope of a possible biological control (sidenote: biological control Biological control is an environmentally sound and effective means of reducing or mitigating pests and pest effects through the use of natural enemies.  Explore https://www.sciencedirect.com/journal/biological-control ) : sugar water laced with Rosenbergiella_YN46 suffices to contaminate the mosquito, with the bacterium then efficiently transmitted transtadially (sidenote: Transstadial transmission The vector (here, the mosquito) retains an agent (in this case, the flavivirus) in its body as it passes from one stage of development to another (here, from aquatic larva to winged adult). Explore Źródło ) , and from generation to generation (in mosquitoes, the gut microbiota is transmitted by the female mosquito to its offspring through larval and adult feeding).

Furthermore, introducing Rosenbergiella_YN46 into the aquatic habitat of larvae, or importing adults already carrying the bacterium, may reduce Dengue transmission in areas where the disease is endemic.

At menopause, the vaginal microbiota may play a key role in women’s gynecological health. 

Under normal circumstances, lactic acid bacteria called Lactobacillus, found in abundance in the vaginal flora, acidify the vaginal environment, helping to balance the microbiota.

How menopause modifies vaginal microbiota 

During the premenopause (the period before menstruation ceases for good, see text box), the drop in estrogen levels leads to a reduction in the glycogen content of the mucosal cells, glycogen being the preferred food of Lactobacillus.

Less well nourished, Lactobacillus become less abundant and lose their dominant position in the flora, which can lead to imbalances in the vaginal 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.   ) ). The reduction in sex hormones is also associated with a harmful increase in microbial diversity. 

Several studies have shown that the loss of Lactobacillus dominance and the increase in bacterial diversity are associated with inflammation of the vaginal mucosa. Inflammation increases the risk of infection, particularly with sexually transmitted infections (STIs), and of precancerous cervical lesions.

While the link between changes in the vaginal microbiota and inflammation has been shown in premenopausal women, no study has yet been carried out to determine whether it persists in the postmenopausal period (see text box). 

Modulating the vaginal microbiota to preserve health?

To document this, a team of US researchers used data from 119 postmenopausal women (average age 61) who had taken part in a clinical trial comparing the effects of estrogen or a moisturizing cream on the vaginal flora. 

They analyzed both bacterial populations and markers of inflammation (cytokines) in the volunteers’ vaginal fluids to determine whether these two parameters were linked. ³

They found that the women whose vaginal microbiota was the most diverse, or the most depleted in Lactobacillus, had the highest levels of cytokines. These two characteristics of the vaginal microbiota are therefore associated with inflammation, as in premenopausal women.

These results are interesting, since they suggest that it may one day be possible, by modulating the vaginal microbiota of postmenopausal women, to limit inflammation of the vaginal mucosa, and thus act preventively to preserve their health.

In surgery, persistent post-surgical pain (or PPSP) is defined as pain that remains significant for at least 3 months after surgery.

It's a condition that affects millions of patients around the world, and one that science is still fairly helpless to tackle, even though we know that there are certain predisposing factors (type of surgery, intensity of pain before the operation, the patient's attitude to pain, genetic factors)

However, a new lead is emerging, one that we might not have thought of at first: microbiota, of the gut rather than the breast, and therefore implicitly the famous gut-brain axis (sidenote: Gut-brain axis Two-way communication network between the gut and the brain, which allows the gut and brain to communicate via three different pathways: 
1. the neuronal pathway (neurons), mainly via the vagus nerve and the enteric nervous system,
2. the endocrine pathway, by secreting hormones such as cortisol, adrenaline and serotonin
3. the immune system pathway, by modulating cytokines The gut-brain axis influences our behavior, cognition (memory), emotions, moods, desires, perception... and pain, among other things. ) .

Thus, manipulating the gut microbiota preoperatively with probiotics or prebiotics could reduce the incidence of PPSP. At least, that's what a preliminary study had suggested, showing that certain bacteria in the digestive tract are associated with pain after wrist fracture surgery. And this seems to be confirmed by an Irish study, ¹ this time on women who had surgery for breast cancer.

Gut bacteria associated with the presence or absence of pain

Three months after their operation, half the women reported persistent pain, while the other half were not particularly affected. This difference was linked to the diversity of their gut microbiota: patients reporting severe pain 1 hour and 3 months after surgery had a less diverse gut flora, compared to women with little pain.

Most importantly, certain bacteria appeared to be associated with the presence or absence of persistent post-surgical pain following breast cancer procedures: women who reported no pain 3 months after surgery had more bacteria known for their beneficial effects (Bifidobacterium longum and Faecalibacterium prausnitzii) in their gut, while women with PPSP harbored more Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii and Roseburia hominis.

Persistent post-surgical pain (or PPSP (sidenote: Persistent post-surgical pain (PPSP) Pain which continues after a surgical operation in a significant form for at least three months, and is not related to pre-existing painful conditions ) ) is as common as it is underestimated: it affects millions of patients worldwide. Predisposing factors include the type of surgery. For example, in the case of breast cancer, 80% of women whose surgery includes axillary lymph node clearance suffer from PPSP.

Previous studies have implicated the gut microbiota in postoperative pain. However, the mechanisms remained unclear: gut dysbiosis could induce an imbalance in the production of microbial metabolites, and play a role in the development of PPSP via the gut-brain axis (sidenote: Gut-brain axis Two-way communication network between the gut and the brain, which allows the gut and brain to communicate via three different pathways: 
1. the neuronal pathway (neurons), mainly via the vagus nerve and the enteric nervous system,
2. the endocrine pathway, by secreting hormones such as cortisol, adrenaline and serotonin
3. the immune system pathway, by modulating cytokines The gut-brain axis influences our behavior, cognition (memory), emotions, moods, desires, perception... and pain, among other things. ) .

To find out more, Irish researchers at University College Cork ¹ conducted a prospective observational study of adult patients undergoing surgery for breast cancer (excluding axillary clearance or reconstructive surgery, which are very painful). Their aim was to determine whether the composition of the gut microbiota was associated with the incidence and extent of PPSP in this cohort of patients.

Less alpha diversity

Twelve weeks after the operation, 21 patients (51.2%) reported no pain, while 20 (48.8%) reported persistent pain. This difference seemed to be linked to the diversity of their gut microbiota: a lower alpha diversity (sidenote: Alpha diversity Number of species coexisting in a given environment ) (3 measures: richness, Shannon index and Simpson index) was observed in patients reporting severe pain 1 hour after surgery and 12 weeks later, compared to those reporting mild pain. On the other hand, there was no difference in beta diversity (sidenote: Beta diversity Rate of variation in species composition, calculated by comparing the number of unique taxa in each ecosystem ) .

Bacteria associated with the presence or absence of pain

But above all, the team highlighted stark differences in the composition of the gut microbiota corresponding to pain, with increased presences of:

• Bifidobacterium longum and Faecalibacterium prausnitzii in women who reported no pain 12 weeks after surgery
• Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii and Roseburia hominis in women with PSPP.

These results seem to support those of previous studies: reduction in the relative abundance of Faecalibacterium prausnitzii in patients with fibromyalgia; reduction of pain after the administration of Bifidobacterium longum in a rat model with arthritis. There is one exception, however: Roseburia hominis reduced visceral hypersensitivity in rats, while it was associated with the presence of PPSP in this study.

More than 80% of urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC). (sidenote: Uropathogenic Escherichia coli (UPEC) E. coli often encoded with additional genes (when compared to commensal E. coli) that boost its pathogenicity (flagellum, toxins, surface polysaccharides, etc.) ) These gut bacteria can migrate from the anus, colonize the urethra, and then spread upwards to the bladder. Previous studies have shown that women suffering from UTIs have an increased abundance of E. coli in their digestive tract, with similarities between intestinal species and those colonizing the urinary tract. 

To assess dysbiosis and other potential risk factors in women with a history of urinary tract infections, researchers enrolled 753 female volunteers aged 18 to 45 who had been diagnosed with a UTI in the previous five years but were otherwise in good health.

Eat a healthier diet

71% of the women were found to have a gut dysbiosis, which was associated not only with recurrent UTIs (sidenote: Recurrent urinary tract infection A recurrent urinary tract infection is defined as two or more symptomatic episodes in the previous six months, or more than three episodes in the previous year. ) , but also with a flora that exhibited multi-resistance to antibiotics.

Another particularity of the population studied was their diet, whether in terms of drinks (less than a liter of water per day, consumption of sugary juices, etc.), food (too many salty products, high-calorie diets rich in added sugars and saturated fats, etc.), or dietary supplements to prevent UTIs.

The researchers believe that these observations support the link between diet and the composition of the gut microbiota. This is consistent with previous studies which found that only 12% of the structural variation in gut microbiota can be attributed to genetic changes, while 57% can be explained by dietary changes.

Microbiota as a new therapeutic strategy

Although the gold standard treatment for UTIs involves antibiotics, in the long term, antibiotics disrupt the gut microbiota (dysbiosis) and favor the emergence of multiresistant microorganisms. Hence the importance, according to the authors, of alternative and complementary therapeutic choices.