Spring goes hand in hand with... sneezing! Itching, tingling, a runny nose, watery eyes... every year, the arrival of spring and high concentrations of pollen bring hay fever back with a bang. Allergic rhinitis—commonly known as hay fever—and its succession of symptoms plague the lives of 40% of the world’s population (sidenote: Cheng L, Chen J, Fu Q, et al. Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res (2018) 10(4):300–53.  Eifan AO, Durham SR. Pathogenesis of Rhinitis. Clin Exp Allergy (2016) 46 (9):1139–51. ) . This complex condition results from a combination of genetic and environmental factors, including an interaction between a respiratory microbiota imbalance and an abnormal and excessive immune system response. But what are the effects of this dysbiosis? And which microorganisms are involved?

An unbalanced respiratory microbiota

To find out, a Chinese team compared respiratory microbiota in nasal samples taken from 28 people suffering from acute episodes of seasonal allergic rhinitis with those of 15 non-allergic subjects. They found no difference between the two groups in terms of microorganism diversity and abundance, but important disparities in their composition. The bacterial genera Moraxella, Haemophilus, Streptococcus and Flavobacterium, predominant in the respiratory microbiota of healthy individuals, had been replaced in allergic individuals by the genera Klebsiella, Prevotella and Staphylococcus. In total, the researchers identified 10 bacterial genera that were over-represented in the latter.

A disturbed metabolism 

The scientists then applied serum metabolomics, a technique that consists in analyzing the concentration of metabolites (sidenote: Metabolites Small molecules produced during cellular or bacterial metabolism. For example, short-chain fatty acids are metabolites produced by intestinal microbiota during fermentation of non-digestible complex carbohydrates (fibers, etc.). 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.  Lamichhane S, Sen P, Dickens AM, et al An overview of metabolomics data analysis: current tools and future perspectives. Comprehensive analytical chemistry. 2018 ; 82: 387-413 ) in serum. This revealed the presence of 26 different metabolites in allergic people compared to healthy people. They also discovered the presence of 16 altered metabolic pathways, including those of arachidonic acids, already known to produce inflammatory mediators involved in some inflammatory diseases, such as allergic asthma.

Hope for individualized treatments?

The combined results of these two approaches confirm the hypothesis that inflammatory reactions of allergic origin influence the balance of respiratory microbiota. More importantly, they provide important candidate biomarkers of potential use in the diagnosis of allergic rhinitis. The authors therefore suggest continuing this work to refine the identification of different subtypes of allergic rhinitis (seasonal/perennial, intermittent/persistent, mild/moderate/severe), which may pave the way for the development of individualized treatments... and an end to the ordeal of thousands of people.

Unfortunately impedes some attempts to stop smoking: former smokers tend to put on weight. On average an extra 4.5 kg on the scales 6–12 months after the last cigarette. Something that discourages the best intentions. Unless our gut microbiota offers us welcome assistance? In any event, this is what is suggested by a recent study in mice.

^{Sources : OMS (sidenote: https://www.euro.who.int/en/health-topics/disease-prevention/tobacco )}

Smoking cessation: a microbiota that carries weight

As in humans, mice exposed regularly to cigarette smoke tend to gain weight after stopping smoking. After a long series of experiments, the researchers seem to have identified the mechanism potentially in play. Some compounds in tobacco (nicotine?) are thought to be able to reach the digestive system of “smoker” mice after traveling in the blood. They are then thought to modify the composition of the gut microbiota. And in fact, it is enough to transplant the microbiota of smoker mice into non-smoker mice to make them gain weight. Something that designates this microbiota as being partially responsible for the kilos gained.

The mechanisms involved elucidated?

But in practice, how is this possible? It would appear that smoking disrupts the delicate balance between the molecules that promote weight gain and others that restrict it. In smokers, the molecule that promotes weight gain is thought to be produced in greater quantities, whilst the molecule that blocks it becomes increasingly scarce. So why don't they get fat? Because the mechanism is gradual, allowing the body time to adjust by associating every cigarette lit to the necessity to eat less. Except that on stopping smoking, this appetite-suppressant effect of the tobacco disappears immediately, while the imbalance in the microbiota that encourages weight gain lasts much longer. Direct consequence: the scales go into panic mode!

Supporting ex-smokers

said Prof. Evan Elinav who led the research team. While waiting to find out how to repair the microbiota of ex-smokers (diet? microbial therapy, postbiotics?) in order to limit weight gain after quitting smoking, this study makes a “weighty” argument for never smoking your first cigarette, or exposing those around you to passive smoking: protecting the equilibrium of the microbiota.

Fish, coral reefs, shellfish and marine bacteria are not the only casualties of microplastics derived from the degradation of plastic bags. Microplastics are now everywhere: in the air we breathe, in the water we drink, and in the food we eat. No-one can escape them, as shown by a research team who found them in 100% of the stools of patients with IBD and also in those of healthy individuals.

CIBD: stools full of microplastics 

From homo erectus... to homo plasticus! Although we have all unwittingly become consumers of microplastics, it seems that we are not all in the same boat. So, depending on the health of our intestines, our stools do not contain the same number, size or type of plastic particles. This study showed that in people with Inflammatory Bowel Diseases (or IBD) such as Crohn's disease or ulcerative colitis, these microplastics were:

• more numerous (around 42 pieces/gram of dry fecal matter vs. 28 in healthy subjects),
• generally smaller (<50 μm),
• and of different origin, with PET (a plastic typically used in bottles of water), polyamide (derived particularly from synthetic textiles) or PVC (pipes, plastic flooring) being more abundant.

The team also noticed that the greater the quantities of microplastics present in the stools of IBD patients, the more severe was the disease. For all that, this does not necessarily mean that microplastics are responsible for IBD. Other explanations are possible. For example, the disease could cause greater retention of microplastics in the intestines, to such an extent that they are found in greater quantities in the stools. The researchers are still working to determine which is the consequence of the other, microplastics or IBD.

Our diet in the firing line

As for knowing where these tiny pieces of plastic come from, the team points to three sources:

• the consumption of bottled water, which goes hand in hand with a doubling of the quantity of plastic in the stools. This is not surprising, if you consider that bottled water contains 22 times more microplastics (especially PET) than tap water. 
• the consumption of fast food, doubtless due to the plastic packaging;
• and exposure to dust, whether at work or elsewhere in life.

Another reason, if it was needed, to prefer home cooking and inert containers (glass jars): not only is it good for the planet, but good for our bodies too.

An additional 4.5 kg in the 6–12 months following smoking cessation, indeed more than 10kg in one year in 13% of ex-smokers: weight gain represents a major obstacle to giving up cigarettes. A team of researchers used a mouse model to assess the potential role of the gut microbiota in this weight gain.

Tobacco, dysbiosis and weight gain

First observation: rodents regularly exposed to cigarette smoke stayed in shape, even with a high-fat, high-sugar diet. On the other hand, as in humans, smoking cessation led to weight gain, unless the mice were given broad-spectrum antibiotics that depleted their microbiota. In question? Compounds linked to tobacco, such as nicotine, appear to penetrate the digestive system of “smoker” mice, causing long-term changes (after cessation) in the bacterial composition of the gut microbiota. With into the bargain, a metabolism better able to extract energy from foods (fewer calories in their feces).

Transfer of the microbiota of “smoker” or “ex-smoker” mice confirms the role of the gut microbiota: the recipient mice (axenic (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. ) and never exposed to smoke) gradually gained weight, unless they had previously been given antibiotics (markedly lower weight gain).

Two metabolites at issue

There remained the task of determining which metabolites were involved. Two molecules with opposite effects were isolated from the thousands of bioactive compounds whose levels varied at the time of cessation:

• dimethylglycine (DMG), manufactured by the intestine and liver from dietary choline, which increases weight gain; 
• acetylglycine (ACG) which has the opposite effect. 

Whereas the two antagonistic molecules allowed the “non-smoker” mice to stay in shape, smoking gradually disrupted this equilibrium (increased DMG production and less ACG production). According to the authors, an “anorexic reaction”, leading to reduced food intake is thought to be set up, to avoid calorie overload. The problem: with smoking cessation, this appetite-suppressant effect disappears whilst the obesogenic dysbiosis and the accumulated metabolites are thought to be slow to reverse. Hence the weight gain.

“The diagnosis of endometriosis starts by talking to the patient” 

Dr. Erick Petit

Do we know when endometriosis dates back to?

Erick Petit : Endometriosis has a long and sinuous—if not tumultuous—history. Even though the symptoms have been described for 4,000 years, it was not until the end of the 19th century that it was recognized as an organic disease. Unbelievably, that means it was left undiagnosed for almost 4,000 years. The first clinical description of endometriosis dates back to 1855 BC, concerning an Egyptian woman. The disease was next listed in the Greek body of clinical literature around the year 500 BC.
That was when the symptoms were clearly catalogued and the association was made with menstruation. The disease was subsequently considered to be a condition of the feminine psyche and was consigned to limbo until the Renaissance. Hysterikos being Greek for “uterus,” the physicians of the time had a field day with this so-called illness that they believed had been entirely made up by what they referred to as “hysterical” women. The pain, however, was very real... 

For centuries, women were imprisoned in the belief that pain was inevitable. They were committed to specially created institutions and marginalized. It was only in the 19th century, thanks to the work of Carl von Rokitansky, a Bohemian pathologist working in Vienna, that endometriosis was histologically confirmed for the first time in 1860.¹

Why is the diagnosis of endometriosis so long and complicated? 

E. P. : The gold standard test is still the endovaginal ultrasound (or an MRI for young girls who have never had sexual intercourse, although this technique is less sensitive and less specific), but I remain convinced that medical imaging does not tell us the whole story. The scans must be compared with the clinical data and the patient should be listened to carefully. That is why, in the RESENDO (sidenote: https://www.resendo.fr/ ) network, we use a clinical questionnaire that contains specific questions and gives a better picture of the pain experienced. In nine out of ten cases, the diagnosis of endometriosis is confirmed. We believe that, first and foremost, listening to the patient and having a real conversation is the basis of the diagnosis. Time constraints mean that nobody can spend even 15 minutes talking with a patient anymore. 

Yet asking patients the right questions is exactly how we can establish a reliable diagnosis and treat women who have in some cases been left undiagnosed for a whole decade!² Not enough large-scale epidemiological studies have been conducted to date, but there are tangible signs suggesting that prevalence has been on the rise over recent years. It is commonly said that one in ten women suffers from endometriosis. It is in fact more likely to be one in seven, or even one in five, women of reproductive age.² 

Does a typical profile exist for women affected by endometriosis? What are the consequences?

E. P. : It is a complex pathology involving many factors. So there is no typical profile. I would say that there are as many forms as there are patients. There is no correlation between the anatomical and clinical findings for this disease. Certain women can have very severe endometriosis anatomically speaking, without experiencing too much pain. Conversely, others with only mild endometriosis may suffer from debilitating symptoms. This illness is the number one cause of hypofertility,² which is the second biggest consequence of endometriosis after pain. We have in fact observed a correlation between the extent of the lesions and fertility. But this is not necessarily linked to pain. 

What are the early signs?

E. P. : The disease appears at menarche. This is why a young girl should be carefully observed at this time. Is the level of pain intense? Does she remain bedridden during menses? Non-attendance at school is also a good indication. Early menarche (before the age of 11) and having a mother or sister who also suffers from endometriosis are risk factors. To avoid leaving the condition undiagnosed and starting treatment too late, I have been campaigning for years to raise awareness about endometriosis among girls between the ages of 11 and 13 during their medical appointments. 

In addition, almost 100% of patients suffering from endometriosis are also affected by some form of irritable bowel syndrome. These symptoms in the digestive system can also be a warning sign of the disease, and they are sometimes the only sign. It is therefore crucial to make gastroenterologists more aware of the condition.

How is it treated?

E. P. : The available care is still very inadequate and is mainly based on hormone treatments. The condition requires multidisciplinary care:  

“Certain clinical signs support the hypothesis of a link between the microbiota and endometriosis” 

Vanessa Gouyot

What links between endometriosis and the microbiota do we know of?

Vanessa Gouyot : Although they are increasingly tangible, these links have not yet been confirmed. To date, no scientific study has been able to formally identify the links between endometriosis and the dysbiosis observed within the various microbiota in the human body.³ However, medical practice has highlighted clinical signs⁴ that support the hypothesis.  We therefore now know, from a dietary perspective, that 90% of women affected by endometriosis also suffer from associated digestive disorders (irritable bowel syndrome or poor digestion in particular). At my practice, I see a great many patients who state that they have an imbalanced microbiota, whether it concerns their oral, gastric and/or gut microbiota. One hypothesis seems to be emerging: endometriosis is an inflammatory disease that could be feeding on the “fertile” inflammatory environment in the digestive tract (i.e., the low-grade inflammation in the gut) in order to develop.  

Could the microbiota nevertheless accelerate the diagnosis of the illness?

V. G. : Endometriosis is a chronic inflammatory disease that is complex and often diagnosed late. The pathophysiology of endometriosis has inspired numerous hypotheses but it has not yet been possible to determine which is the most robust. The gut microbiota is a promising line of investigation that is offering new perspectives for research to enhance our understanding of what causes this pathology.⁵ Eventually, what we might consider is not necessarily an assessment of endometriosis via the microbiota, but instead improved diagnosis of digestive inflammation^6,7 through the assessment of the microbiota.  

Endometriosis can only be diagnosed by taking a holistic approach. Today when treating a new patient suffering from endometriosis, we review her whole lifestyle, i.e., her diet, including liquid intake, the quality of the air in her living environment, etc. We even go right back to birth, because we know that the first months of life are pivotal to the formation of the microbiota. When I take their history, I also question my patients about any digestive system disorders existing prior to menarche. Nearly 90% of my patients who suffer from endometriosis were also affected by disorders of the digestive system before menarche, although the statistic should be analyzed objectively. 

My mission is to enable my patients to understand that the digestive tract is a passage which is permanently under assault. This aggression may alter the digestive system and lead to inflammation. This holistic approach should be accompanied by a multidisciplinary component including family doctors, gynecologists, pain specialists and osteopaths, etc. Every effort should be made to avoid leaving patients undiagnosed. I am convinced that a coordinated and multidisciplinary care pathway is the key to early diagnosis and improved treatment for patients with endometriosis.  

Could the microbiota eventually be used in the search for future treatments?

V. G. : Research into the microbiota8,9is making rapid advances.  It is a source of much hope and should, in the medium term, reduce the time to diagnosis for endometriosis patients suffering from disorders of the digestive system. Probiotics currently represent one of the solutions that can be offered to restore the gut flora and reduce inflammation. The problem is the knowledge deficit regarding their use. 

It should be pointed out that taking probiotics alone is not a cure for intestinal hyperpermeability. It can help, but it does not restore the condition of the gut. Certain patients judge that they do not need them, others take them but not regularly, and others have abandoned their course of priobiotics because they felt that the treatment had no effect. Time must be set aside to explain, reassure, and also adjust treatment according to needs. The objective of probiotic therapy is to give our patients the tools to manage their condition, so that they become more attentive to signals from their body. Helping our patients live a normal life with less symptomatic pain is the ultimate victory for us. 

“Diet plays a major role in relieving a painful digestive system associated with endometriosis”

Dr Laetitia Viaud Poubeau

In the case of endometriosis, can nutrition play a role in restoring balance to the microbiota? 

Laetitia Viaud Poubeau : An anti-inflammatory diet, such as a Mediterranean diet for example, can only be beneficial to the gut microbiota for those suffering from endometriosis. 
This type of diet is rich in vegetables, fruits, pulses and whole grains, but also in Omega-3 fatty acids, which are both prebiotics and anti-inflammatory, and it encourages the development of a flora that is eubiotic, rich in bifidobacteria and lactobacilli.^10-12 

Such nutrition optimizes the synthesis of short-chain fatty acids, such as butyrate, which fuels the microbiota and the cells in the gut.^13,14 
 

There are three benefits:  it promotes a balanced gut microbiota, combats intestinal permeability and thereby reduces the underlying low-grade inflammation.

What foods should be excluded from the diets of endometriosis patients?

L. V.-P. : The “Western diet,”^11,15 which is rich in processed foodstuffs, refined sugar, salt, saturated fats (red meat for example) and trans fat (such as pastries),¹⁶ is detrimental to the balance of microbes in the gut. This type of diet causes gut dysbiosis and low-grade inflammation. Drinks like sodas, fruit syrups, fruit juice and strong alcoholic beverages should also be avoided. 

Studies have also demonstrated the benefits of reducing the intake of gluten^11,17,18 which, by activating zonulin (sidenote: Zonulin Protein involved in the regulation of epithelial and endothelial permeability.
It is secreted by the liver, among other organ tissues, and at the surface of enterocytes in the intestinal mucosa, acting on the tight junctions. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-100. ) , opens tight junctions and increases systemic inflammation. 

On the other hand, the consumption of dairy products does not seem to put individuals at a higher risk of developing endometriosis.^19,20 The levels of growth hormones that they contain may, however, be conducive to the relative hyperestrogenism of patients suffering from endometriosis.²¹ Additionally, hypersensitivity to milk proteins maintains low-grade inflammation.¹¹

Attention should also be paid to the impact of additives, endocrine disruptors, antibiotics used in the agri-food industry, pesticides and other chemical pollutants. Many of these are found in our foods and affect the balance of our microbiota. 

What are the consequences of a Western-style diet on the gut microbiota? Is this diet responsible for the gastrointestinal disorders observed in endometriosis? 

L. V.-P. : Gut dysbiosis caused by a Western diet is conducive to the development of gram-negative bacilli. These bacteria have a lipopolysaccharide (LPS) molecular pattern that causes metabolic endotoxemia and triggers low-grade inflammation via the activation of the TLR4 receptor.^11,22,23 

This induced dysbiosis results in discomfort in the gut, which can range from constipation to diarrhea. We have also observed bloating, intestinal spasms and flatulence that can be odorous to varying degrees, which all add to the discomfort of patients suffering from endometriosis. 

In this case, a diet excluding FODMAPs (Fermentable Oligo- Di- Monosaccharides and Polyols) or a digestive-sparing diet can be introduced during the initial phase of balancing patients’ dietary habits in order to provide rapid relief.²⁴ The digestive-sparing diet is a model that aims to reduce inflammation and help the gut mucosa to heal. It is based on a set of simple dietary and lifestyle rules: excluding raw vegetables and raw fruits; limiting citrus fruits and cruciferous vegetables; cutting out lactose, gluten, and irritant beverages like coffee, strong alcohol and sodas. It can be followed for 4 to 6 weeks, is less restrictive than the FODMAP-free diet and above all does not alter the gut flora balance like the FODMAP-free diet does, which reduces the endoluminal concentration of bifidobacteria.²⁵ 

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Our increasingly urban lifestyles mean that our children have less and less contact with nature in their day-to-day surroundings. This has consequences for the microbiota, with the microbiota of children living in rural areas differing from that of children in urban areas. This could partly explain the higher incidence of autoimmune diseases in city children.

Microbiota: nature always wins

This study of the microbial composition of floor surfaces in daycare centers and of children’s gut, salivary, and skin flora showed that greening these spaces had a positive impact on microbial composition. The children’s gut, oral, and skin microbiota saw long-term shifts towards a new equilibrium involving increases in the relative abundance of beneficial bacteria.

Their microbiota also contained fewer potentially pathogenic microorganisms. 

This is important, since we know that a balanced microbiota contributes to the proper functioning of the immune system.

When biodiversity rhymes with immunity 

These effects observed after two years are very promising and potentially form the basis of a strategy for optimizing urban spaces. Reintroducing biodiversity into urban environments could help reduce the quantity of pathogenic microorganisms in cities, which may in turn lower the incidence of diseases linked to microbiota imbalances. However, further studies are needed to confirm any real impact on the incidence of immune-related diseases. In the meantime, feel free to let your children roll around in the grass!

While otitis is common in childhood, it seems to disproportionately affect the children of indigenous peoples (sidenote: Les enfants aborigènes australiens seraient 5 fois plus à risque d’otite sévère de l’oreille moyenne que les enfants australiens non aborigènes. Gunasekera H, Knox S, Morris P et al. The spectrum and management of otitis media in Australian indigenous and nonindigenous children: a national study. Pediatr Infect Dis J. 2007 Aug;26(8):689-92. ) . The problem is that studies seeking to characterize the microorganisms associated with the disease in these populations have so far looked for known otopathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) or have mainly used culture techniques that do not reveal the presence of microorganisms that are difficult to cultivate.

Moraxella, a marker of previous otitis?

They found a greater relative abundance of Moraxella in children who had previously had an ear infection. This was so even in children who were free of otitis at the time of the analysis and may be due to a lasting remodeling of the nasal microbiota following a previous case of otitis. Moreover, the abundance of Moraxella in the nasal microbiota was negatively correlated with that of Staphylococcus, a bacterial genus found in greater abundance in children with no infectious nasal discharge. In vitro data suggest that certain species of Staphylococcus may inhibit Moraxella, which could explain the negative correlation observed.

A protective duo of microorganisms?

Furthermore, in the children not suffering from an ear condition at the time of the study, a positive correlation was observed between Dolosigranulum and Corynobacterium. This correlation was also found in children with no infectious nasal discharge, leading the authors to consider this co-colonization as potentially protective against pathogens such as S. pneumoniae and guaranteeing the health of the upper respiratory tract and ear.

Towards the identification of new otopathogens

In contrast, Ornithobacterium was found in greater abundance in children with serous otitis than in the children who had never had otitis. It may thus be a new otopathogen. Its presence was correlated with that of two other bacterial genera, Dichelobacter and Helcococcus, whose effects on nasal and ear health have yet to be defined.

Bottled, tap, filtered, or well water: not all water is the same when it comes to origin (groundwater, surface water, etc.), treatment (filtration, disinfection, etc.), and therefore chemical, mineral, or microbial composition. Despite being consumed in far greater quantities than food, water is often overlooked when it comes to scientific studies on diet and the microbiota. The effects of certain foods (dark chocolate, avocado, tea, etc.) and beverages (soda, alcohol, beet juice, etc.) have been studied carefully, but scientists have been reluctant to look at the role played by water.

A qualitative effect...

The results? The source of our drinking water is a key factor behind variations in the composition of the gut microbiota. Its influence is comparable to that of alcohol consumption or diet. Each type of water consumed corresponds to a different gut microbiota signature. Do you mainly drink well water? Your gut microbiota is likely to be more diverse than if you drink tap, filtered, or bottled water. Moreover, your digestive tract probably hosts more bacteria from the genus Dorea and fewer Bacteroides, Odoribacter and Streptococcus. What’s behind the difference? It may be because well water has greater microbial diversity than tap water due to the lack of systematic disinfection.

... and a quantitative effect

But it’s not all about where our water comes from. Quantity also plays a role. The gut microbiota of low water drinkers (from all sources) differs from that of high water drinkers. For example, low water drinkers have a greater abundance of Campylobacter, a bacterium associated with gut infections. This should encourage us to lift our glass more... provided we’re only drinking water!

“Endometriosis: 4,000 years of prejudice and misdiagnosis”

Dr. Erick Petit

When was endometriosis first described? 

Erick Petit: The disorder has been plaguing the lives of women for 4,000 years... yet it was only recognized as an illness a century and a half ago ! The first officially recorded “patient” was an Egyptian woman in 1855 BC. We can find references to endometriosis as far back as the 6th and 5th centuries BC, posited by Hippocratic physicians who listed the symptoms in detail. After that period, we can observe what appears to have been a kind of medical cover-up. Until the Renaissance, endometriosis was judged to be nothing more than an element of the feminine psyche.

This is supported by the etymology. The word “uterus” originates from the Greek hysterikos and the medical profession was quick to establish the diagnosis of “hysteria”. The illness was seen to be an imaginary condition entirely made up by women, who were actually in agony. It is difficult to believe that it was not until 1860 that the condition was shown to be related to the endometrium (sidenote: Endometrium The layer of tissue that lines the uterus.  NCI Dictionaries_Endometrium   ) , hence the name endometriosis¹, by Carl von Rokitansky, a Bohemian pathologist working in Vienna. It is currently estimated that at least one in ten women of reproductive age suffers from endometriosis. It is in fact more likely to be one in seven, or even one in five, women of reproductive age².

How is endometriosis diagnosed? Why is it so complicated?

E.P.: In reality, the diagnosis is quite simple: patients fill out the clinical questionnaire that I drew up, which is available to them at their appointments in RESENDO (French network). It contains a number of questions, some of which concern the types of pain experienced. I can make a reliable diagnosis based on the results of this questionnaire. The diagnosis is in fact confirmed nine times out of ten. This saves time and is also reassuring for the patient. Today, the way to identify endometriosis is through talking and listening to patients. There are women who have been waiting for a diagnosis for so many years, over a decade in some cases²! They are still victims of prejudices that date back 4,000 years, according to which women’s periods are naturally painful. I have set out to dispel this myth and highlight the fact that endometriosis is a medical condition.

The next step, what I would call the gold standard test is, of course, an endovaginal ultrasound carried out by a specialist (or an MRI (sidenote: MRI Magnetic Resonance Imaging. ) for young girls who have never had sexual intercourse, although this technique is less sensitive and less specific). This test shows the lesions and their locations. However, I would like to stress that medical imaging alone is not enough. There is actually no correlation between symptoms and lesions with this illness. This means that some women can have very extensive endometriosis yet hardly suffer, but conversely, others with much milder endometriosis may experience extreme pain. 

Do different forms of endometriosis exist? Are some forms more serious than others?

E.P.: There are as many forms as there are patients! This is why it is so important to properly map out their pain to fine-tune the diagnosis and treatment. The main consequence of this illness is infertility, depending on the location of the lesions. We have observed a correlation between the anatomic extent of the condition and fertility. But this is not necessarily linked to pain. Endometriosis is the number one cause of hypofertility!²

What are the early signs?

E.P.: The illness appears after the first menstrual period. A young girl should be carefully observed at this time in order to assess the intensity of the pain, to see if she has to go lie down, if she is not able to attend classes, etc. We know that periods starting early, before the age of 11, represent a risk factor for the illness, as well as having a mother or sister who also suffers from the condition (genetic factors). This is why I campaign for raising awareness about endometriosis among girls aged between 11 and 13. This is the only way to ensure cases are not left undiagnosed. There are also effects on digestion that should not be neglected: the near-majority of my patients suffer from some form of irritable bowel syndrome. It is therefore important to make gastroenterologists aware of the illness!

What is patient care based on?

E.P.: Treatment is still very inadequate and is based on a multidisciplinary approach:

“The gut microbiota, undoubtedly a missing piece in the endometriosis puzzle”

Vanessa Gouyot 

Is there a link between endometriosis and the microbiota? 

Vanessa Gouyot: To date, no scientific studies have been conducted that confirm any links between endometriosis and imbalances within the various microbiota (intestinal, vaginal for example) in the human body. However, there are certain clinical signs that support this hypothesis. We now know that 90% of women affected by endometriosis also suffer from associated digestive disorders (irritable bowel syndrome in particular). This figure is borne out in my practice where I am seeing more and more patients who appear to be experiencing gut imbalance, called dysbiosis, in the digestive tract: sometimes oral, sometimes gastric and/or intestinal 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 role of our microbiota is to protect us and form a barrier. But if 90% of women suffering from endometriosis have digestive disorders, that means that there is an associated inflammation of the digestive system... My mission is to enable my patients to understand that the digestive tract is a passage which is permanently under assault (by food and drink, among other things). This aggression may alter the digestive system and lead to inflammation. The human body should be seen as a big emergency response center regularly sending out units to provide aid.

However, if all the units are dispatched to handle a permanent case of inflammation in the gut, then they cannot respond to all the other alerts. All these alerts form a “background noise” of inflammation, i.e., chronic inflammation, which is thought to facilitate the onset of other conditions, such as endometriosis.

Given the digestive system symptoms observed in patients suffering from endometriosis, could the microbiota help diagnose the illness more quickly?

V.G.: Endometriosis is an inherently complex illness that is particularly difficult to diagnose and should be handled with great humility and some caution. The mechanisms of the illness have inspired numerous hypotheses but it has not yet been possible to determine which is the closest to reality. The role of the microbiota is one hypothesis among many. The fact is that research into the microbiota is moving forward and this is bringing much hope to patients, but we should not get ahead of ourselves. Something to consider is that rather than attempt to assess cases of endometriosis via the microbiota, we could instead assess the microbiota to make a better diagnosis of patients’ bowel inflammation and their digestive disorders³. Endometriosis care requires a global and multidisciplinary approach.

Today, when taking on a new patient suffering from endometriosis, we investigate the finer details of her diet, what she drinks and also her living environment. These are all factors that could prove aggressive to the digestive system and lead to an imbalanced gut microbiota.

Could the microbiota be useful in the search for future treatments?

V.G.: Progress has been made in research on the microbiota^4,5 and this will, in time, significantly improve the quality of life of patients with endometriosis who suffer from digestive disorders⁶. In the meantime, as we wait for future medical breakthroughs, taking probiotics remains one way to restore normal gut microbiota function and reduce inflammation. The problem is the lack of information. Some of my patients do not see probiotics as necessary, others take them sporadically, and then others come back to me to say that they do not work.

Different cases require specific explanations for each patient. Remember that the context is important when taking probiotics and recommendations from an expert are required. There are very many strains of probiotics that can have beneficial effects on endometriosis. The objective of probiotic therapy is to give our patients the tools to manage their condition, so that they become more attentive to signals from their body and so that they can finally achieve acceptable levels of comfort. Getting them back to a normal life with less pain is the ultimate victory for us.

“Yes, diet can relieve a painful digestive system associated with endometriosis”

Dr. Laetitia Viaud Poubeau

Can a healthy diet help to restore balance to the gut microbiota of women suffering from endometriosis? 

Laetitia Viaud Poubeau: In cases of endometriosis, a Mediterranean-type diet, i.e. a diet rich in vegetables, fruits, pulses, and whole grains, but also Omega-3 fatty acids, which are both prebiotics and anti-inflammatory, can only be beneficial to the gut microbiota. A diet like this with anti-inflammatory properties promotes the development of eubiotic flora (sidenote: Eubiotic flora A “balanced” flora.  Iebba V, Totino V, Gagliardi A, et al. Eubiosis and dysbiosis: the two sides of the microbiota. New Microbiol. 2016 Jan;39(1):1-12. ) , rich in bifidobacteria and lactobacilli^7-9.There are many benefits to this type of diet: it helps to restore balance to the gut microbiota, combats intestinal permeability effectively and thereby reduces inflammation.

What foods should be avoided by endometriosis patients?

L. V.-P.: What we refer to as the “Western diet”^8,10, a diet rich in processed foodstuffs, refined sugar, salt, saturated fats (red meat for example) and trans fat (such as pastries),¹¹ is particularly bad for the gut microbiota. The Western diet can cause gut dysbiosis that leads to varying levels of complications in the body over time. Strong alcoholic beverages and drinks like sodas, syrups, and fruit juice should also be added to this list of foodstuffs to avoid because they are particularly rich in sugar and/or sweeteners. Some studies also demonstrate the benefits of reducing the amount of gluten in the diet, since it is thought to contribute to the inflammation involved in the illness.^8,12,13

On the other hand, opinion is more divided when it comes to the consumption of dairy products. They do not appear to put people at a higher risk of developing endometriosis^14,15. The levels of growth hormones that they contain may, however, be conducive to hyperestrogenism (sidenote: Hyperestrogenism Normal or high levels of estrogen secretion, but which continues for longer than the secretion of progesterone.  Norman Lavin (1 April 2009). Manual of Endocrinology and Metabolism. Lippincott Williams & Wilkins. p. 274. ISBN 978-0-7817-6886-3. Retrieved 5 June 2012 ) in patients suffering from endometriosis¹⁶. Additionally, hypersensitivity to milk proteins maintains a “background noise” of inflammation⁸: this means permanent, chronic inflammation. 

Additives, antibiotics used in the agri-food industry, endocrine disruptors, pesticides, and other chemical pollutants that we find in our food should also be treated with caution because they can affect the balance of our microbiota.

What are the consequences of a Western-style diet on the gut microbiota? What are the dietary alternatives?

L. V.-P.: Gut dysbiosis caused by the Western diet will result in intestinal discomfort, which can range from constipation to diarrhea. In many women suffering from endometriosis, we have also observed bloating, intestinal spasms and flatulence that can be odorous to varying degrees. 

We then recommend a FODMAP (sidenote: “Fermentable Oligo- Di- Monosaccharides and Polyols”: Fermentable carbohydrates. ) -free or digestive-sparing diet in order bring quick relief to patients¹⁷. The digestive-sparing diet is based on a set of simple dietary and lifestyle rules: excluding raw vegetables, raw fruits, lactose, gluten, irritant beverages like coffee, strong alcohol and sodas, limiting citrus fruits and cruciferous vegetables, etc. It can be followed for 4 to 6 weeks, is less restrictive than the FODMAP-free diet, and above all does not alter the balance of the gut flora¹⁸.

They support this article:

BMI 22.05

A sleep-brain-gut linkage. That is what a recent study has found. We already knew that in adults, sleep and gut microbiota were doubly interrelated: a deterioration in sleep modifies the composition of the gut microbiota and, conversely, the microbial composition of the gut impacts sleep. But we did not previously know the age at which this two-way link became established between sleep and gut microbiota, or what the potential consequences on development might be.

This was what justified this longitudinal study involving 162 healthy infants at 3, 6, 12 and 24 months of age.

There is a connection between sleep and gut microbiota as early as 3 months of age

First confirmation: the composition of the gut microbiota does indeed start to change as of 6 months of age. The majority of the children in the study experienced a change in flora which went from predominantly Bifidobacterium (enterotype A) to a microbiota rich in Bacteroides (enterotype B), with increased alpha diversity (sidenote: α diversity A measurement indicating the diversity of a single sample, i.e. the number of different species present in an individual. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010 Jan;4(1):17-27. ) .

Above all, the study demonstrates a link between sleep habits and gut microbiota from as early as 3 months: 

• Daytime sleep (duration, number of naps and their regularity) has a negative association with bacterial diversity: infants who sleep the most during the day have less bacterial diversity;
• Nighttime sleep fragmentation and variability are linked to bacterial maturity and enterotype: infants with more mature gut microbiota have higher levels of activity at night (waking up more often during the night). Additionally, their enterotype does not change from enterotype A to B between the ages of 6 and 12 months.

Sleep, brain and gut: all linked?

The brain activity analyzed using the nighttime electroencephalograms at the age of 6 months proved to be rich with useful findings. 

First finding: infants with predominantly Bifidobacterium flora showed less slow-wave sleep (“light sleep”);
Second finding: the quality of sleep at 6 months of age can be used to predict the bacterial diversity of the gut microbiota at age 1. The presence of more theta waves at 6 months is a sign that there will be lower bacterial diversity at 12 months.

Lastly, the gut microbiota at 6 months and above all sleep at 6 and 12 months of age predict the behavioral development of the child at 24 months.