Ina Schuppe Koistinen, PhD is a microbiome researcher, Associate Professor affiliated with Karolinska Institutet, and innovation strategist specializing in microbe–host interactions and their role in women’s health, fertility, and healthy aging. Her research explores how microbial ecosystems influence inflammation, reproductive function, epithelial barrier integrity, and long-term health trajectories.

She is the founder of Beyond Oneness Consulting, advising biotech, medtech, and pharmaceutical companies on translating microbiome science into clinically and commercially viable interventions. Ina has co-founded and led a deep-tech biotech startup developing microbiome-based therapies and has contributed to the clinical and regulatory development of antibiotic-free approaches to treating vaginal dysbiosis.

Her work bridges microbial ecology and translational medicine to harness beneficial microbes to improve reproductive health, extend healthspan, and prevent chronic inflammatory conditions. In addition to her scientific work, she is the author of the popular science book Vulva: Facts, Myths, and Life-Changing Insights and an accomplished visual artist whose work explores the intersection of biology and human experience.

A crash course on the microbiome

So I start with a little crash course on the microbiome. So what is it we actually are talking about?

But maybe you have never thought about that, but humans actually never existed without microbes. They were on the world long before us and we developed in total symbiosis with microbes. That means bacteria, viruses, archaea and other small, small, one single celled organisms in our bodies, in and on our bodies.

So we have about 200 or 20,000 human genes and maybe up to two, 20 million microbial genes. So that means they really outnumber us. And it's like an inner pharmacy, which is producing lots of components that are essential for our health.

And the best thing about it, we actually have a possibility to influence it.

• We can't change our genes.
• We are born with them.
• But we actually can change our microbiome by our lifestyle choices, our diet choices, and many other things I'm going to talk about.

The gut microbiome

The microbiome that is studied most is the one we have in our gut. And in the gut, we have about 1.5kg of microbes, which is a huge number. It's almost like the weight of our brain.

One thing is that we think about the gut microbiome. The more diverse, the more different species, the healthier we are. And we also are very individual. So we overlap in maybe 99.9% of our genes. But in the microbiome we only overlap like one third. So you have a very individual signature.

And the microbiome in the gut affects actually all parts of the body.

• It affects our skin
• It affects our brain
• Other organs
• And also the vagina

How the microbiome is established

So when we are born we are seeded with the microbes of our mothers. So we call that a vertical transmission.

And there are differences. If you are born with, vaginal delivery or are born with a C-section, but these differences are kind of going away within the 2 to 3 years of age.

And there are many, many sources to get colonized by microbes, by breast milk, for instance, that contains up to 200 different species of lactobacilli and Bifidobacteria, which are essential for the health of the baby.

But then you have kind of keep a relatively stable microbiome for many years of your life, unless you use antibiotics or affected by very severe infections.

Factors that influence the microbiome

But there are many other factors that influence like our lifestyle and our age.

Also:

• If we live in close nature
• In close relation to nature
• To animals
• And how big the families are

The vaginal microbiome and good health

And, when we think about the vaginal microbiome, then we can say that a microbiome that is dominated by lactobacilli is the one that is associated with good health. So it's different from from the gut.

But these lactobacilli are like the superheros of the vagina because they reduce the pH and by that prevent infection or growth of other bacteria or pathogens.

They also produce other antimicrobial components, such as hydrogen peroxide or bacteriocins that are small peptides that kill off bacteria. They are very kind of adherent to the epithelium or to the layer of the vagina and also have a very close interplay with the immune system.

Changes across life stages

So the vagina microbiome changes during the life course of a woman or a girl.

At birth and during childhood

So when the baby girl is born, the girl or still have the estrogen or the female sex hormone levels of the mother in her blood. And, since the microbiome is very much influenced by estrogen levels. So this will help the girl to establish a microbiome in the vagina that is dominated by lactobacilli.

But since the girl is not able to produce their own estrogen yet, it the microbiome will get more diverse, during childhood.

Puberty and fertile life

But then during puberty and the estrogen levels rise, this microbiome is reestablished with lots of lactobacilli. And that is a good thing.

And that will be kept through the entire fertile life of a woman and also during pregnancy with increasing estrogen levels, the microbiome gets more beneficial and more stable, and that also contributes to healthy pregnancies and less complications.

Menopause

During the menopause or prior to menopause. And after that, then the levels decrease and also the microbiome gets more diverse.

Other factors influencing the vaginal microbiome

There are also other factors than just estrogen that influence the microbiome.

The gut microbiome

It is the gut microbiome. Because the bacteria in the vagina are originally seeded from the gut. We don't understand today the precise mechanisms, how the immune system supports the transfer to the vagina.

But the healthy gut microbiome is important, and a healthy gut microbiome is influenced by our diet. So that is very important.

Menstruation

Menstruation per se is important because if you have blood in the vagina, then the pH level will increase because blood has a neutral pH of seven, and also the nutrients for the bacteria will change. And that is not in favor of lactobacilli.

Pregnancy

Pregnancy influences as I already mentioned.

Sexual intercourse

Sexual intercourse influences the same reason as for menstrual blood. The change of pH and also different nutrients are added to the vaginal environment if you have unprotected sex.

Lifestyle and hygiene

Lifestyle and hygiene is very important.

So my recommendation is always:

• Just to wash your intimate places with lukewarm water
• Maybe a specific mild soap
• And not use any perfumes or any harsh detergents
• And especially not using any of these vaginal douching techniques where it's a lot of advertisement for

Diseases and drugs

And diseases and drugs to influence the microbiome as well.

Risks linked to low lactobacilli levels

So women that are deficient of lactobacilli in the vagina are at higher risk for reproductive diseases. And also adverse obstetric outcomes. And that's why this is so important.

And that's why this is so important for young girls like Camille to understand that we have to take care of our microbiome, support it in the best way.

So we are protected from:

• Infections
• Reduced fertility or difficulty getting pregnant
• Pregnancy complications
• Pelvic inflammatory diseases
• The malignancies that would come with HPV infections for instance
• Urinary tract infections

Microbiome dynamics during menstruation

So during the menstruation, we have studied in detail how the microbiome shifts and what the dynamics are.

And this is from a recent publication of our lab where we could show in blue, lactobacilli in the vagina. And then there are samples from individual women. Each day during the menstrual cycle, you can see that a big proportion of women, they have a stable microbiome with lactobacilli.

But there is also a proportion that has:

• Dysbiosis
• Or, kind of a shift to more pathogenic bacteria during bleeding
• So during menses
• And there are others that have a dysbiotic microbiome, during the whole period

So it is very important to understand those dynamics and fluctuations, especially when you do assign drugs and treatments, because the microbiome is not a static environment.

Take-home messages

So my take home message here is:

• Remember we are ecosystems.
• The microbiome is a key driver of our health and longevity.
• The gut and vaginal microbiomes do regulate immunity, metabolism and the barrier function.
• And that's why they are so important for our health.
• An imbalance of the microbiome thus fuel inflammation, disease risk, and also accelerated aging.
• We have a chance to influence our microbiome by lifestyle choices, but it's also formed by hormone levels and the environment we live in.
• The best support for the microbiome is a diet that is rich in vegetables and dietary fibers, and also in fermented foods that support our microbiota.
• And the vagina, per se is an amazing organ.
• It actually cleans and protects itself through natural discharge and a balanced vaginal microbiota.
• So it's important for all of us to take good care of it.

Question n°1

In the assembly, there's a lot of parents of teenagers and also behind the screen, and we would like to know from your point of view, what are the most important message, parents and teenagers should know about the microbial microbiome at puberty? 

Expert's answer

I think the most important message is that girls should be aware of the discharge. And that discharge changes during your tween puberty. And also not kind of, washing with very strong detergents and destroying the microbiome. So the best is really to let the vagina do the job herself because of the discharge, it's cleanses. And if we destroy the environment with perfumes or products that kind of, designed to put shame on female bodies, we will just, kind of destroy that balance. So be aware of treating it gently and keep the balance. 

Question n°2 

And you talk about the discharge and the maybe order, but how can we help, a teenage girl to understand what is “normal” versus when they should consult, a doctor?

Expert's answer

Yeah, this is very difficult. And I think it's general, as you also put on your original slide here, breaking taboos because we don't talk about it, but we need to talk about it because if we don't teach our daughters what is normal, how should they know? And in general it is if there is a very, very strong odor, if there is itching or some other symptoms that are disturbing, then you should see a doctor and not just wash more, use more soap and all these things that are kind of intuitive but are counterproductive for the microbiome.

Question n°3

And so if you have to give 1 or 2 simple tips to help protect the microbiome during adolescence, what would they be?

Expert's answer

Yeah, I already mentioned the tips. Yeah. To avoid perfumes and soaps I think that's the most important. And also just to not to be ashamed. Yeah. And and just to see it as a natural part of your body and don't believe in all this rubbish that is on social media that your vagina should smell like pineapple, that I mean, there is so much misinformation out there. Don't believe it.

Question n°4

And then you mentioned in your talk that, there's a lot of factors influencing the the vaginal microbiota. How do hormones and first period shape the microbiota is it like, a balance ? What's happens?

Expert's answer

I mean, during puberty, the, estrogen levels or the female sex hormone levels in blood increase and that estrogen makes that the cells that line the vagina produce more glycogen. And glycogen is a nutrient for, for lactobacilli. So they are kind of the biology is designed to make lactobacilli grow to protect the vagina. And that's a natural process. And we should just kind of leave it there.

Professor of Gynaecology and Reproductive Sciences at the University of Edinburgh, Prof. Horne is Director of the Centre for Reproductive Health and Honorary Consultant Gynaecologist at NHS Lothian. A leading expert in endometriosis and pelvic pain, he has published over 200 peer-reviewed articles. He serves as President of the World Endometriosis Society, Trustee to Endometriosis UK, and Specialty Advisor to the Chief Medical Officer of Scotland for Obstetrics and Gynaecology.

Endometriosis: definition and prevalence

So I hope, everyone here has heard of endometriosis, particularly, because this is Endometriosis Awareness Month. But I think particularly because this is a really common condition, it's said to affect, 1 in 10 women and those assigned female at birth. That's the equivalent of an estimated 190 million individuals worldwide.

Endometriosis is a condition that's defined by the presence of tissue, like the lining of the womb, outside of the womb, outside of the uterus, and that tissue can be found almost anywhere within the body, can be found within under the diaphragm. It can be found on the umbilicus. It can even be found within the lung.

Main pelvic subtypes

But the commonest site for endometriosis is within the pelvis, and there are three, pelvic subtypes.

• The commonest, which accounts for around 80% of the disease that we see is called a superficial peritoneal endometriosis. This is when you get, diffuse endometriosis lesions around the pelvic sidewall.
• Endometriosis can also exist as a ovarian disease. This is a cystic form of endometriosis, often called “chocolate cysts” because they have altered blood inside them. And these cysts appear on the ovaries.
• Or you can choose this as a deep disease. And deep disease is a more fibrotic and nodular disease that often involves the bowel or the bladder

Symptoms and associated conditions

The endometriosis can cause a large number of different symptoms. Probably the most recognized are painful symptoms.

• Painful periods are often very severe and debilitating.
• Pain outside of periods.
• Pain with sex.
• Pain with menstruation.
• Pain on defecation.

But it can also, cause a range of other symptoms such as diarrhea and constipation, other urinary symptoms, fatigue, depression, and around a third of people who experience endometriosis, suffer from infertility, difficulty getting pregnant.

It's also associated with other gynecological conditions out adenomyosis and fibroids. Is associated with other chronic pain conditions, other inflammatory conditions, and in later life, it can put people at greater risk of conditions like cardiovascular disease and also certain types of cancer.

Diagnostic approaches

Endometriosis is diagnosed using a number of different, approaches, a history and examination, is important. Imaging is important. And laparoscopy or keyhole surgery, is often necessary. And this is carried out under a general anesthetic to try and visualize the disease and often take, a biopsy of the disease.

And there are a number of emerging tests which hope to supersede, the invasive nature of a laparoscopy. Both saliva and blood in particular, have been studied.

Limits of current diagnosis

But one of the problems, with the endometriosis, diagnosis is that none of these approaches are particularly effective.

So, for example:

• a clinical history, an examination isn't able to differentiate between the three subtypes of Endometriosis that you can see here.
• Imaging is only effective for ovarian and deep disease and isn't effective to detect superficial peritoneal disease.
• Surgery, of course, is dictated by, access.
• They're often, huge waiting times for patients to have surgery.
• Even with a laparoscopy, sometimes disease can be unrecognized or microscopic disease can be difficult to pick up.

The biopsy, is also not always helpful. It can be complicated by artifacts, and around 50% of biopsies taken for Endometriosis don’t confirm the disease.

I know whilst there's been a lot of work looking at different, biomarkers, sadly none of these have been, validated in such that they can be, brought into clinical practice, at present.

The diagnostic journey

So patients with Endometriosis often have this awful, prolonged diagnostic journey estimated to be around, eight years in most countries across the world.

So they might:

• See multiple different, healthcare professionals in the primary care setting
• Perhaps go to accidents and emergency and casualty departments
• Before they actually see a specialist, a gynecologist.

And even when they see a gynecologist, they might have to undergo multiple, imaging tests. They might see other specialties, before they have a definitive diagnosis. And importantly, before they're given appropriate treatment for the condition.

Treatment approaches

So how is endometriosis diagnosed? Well, it can be diagnosed in a disease specific way if you like. And that can be either by surgery and this is laparoscopic or keyhole surgery to remove, the lesions. Or it can be treated with a range of different hormone treatments.

And the rationale for using hormones is: we know that Endometriosis is an estrogen dependent condition. And if you give hormones that suppress, ovarian, estrogen production, it's been shown to help with this, the painful symptoms associated with the condition.

And alongside that, we often, offer pain management strategies, non-steroidal anti-inflammatory neuromodulator drugs like nortriptyline and pregabalin, and then complementary therapy, if you like, like physiotherapy, psychological, treatments. And then patients themselves often use things like tense machines, heat and cool packs and dietary changes, which I'll talk about in a minute.

Surgery

So let's look, first of all, at surgery for Endometriosis.

Well, the surgery, although it's performed laparoscopically can be either performed by excision or ablation with, for example, late, lace or heat. And there's a huge amount of debate, particularly across the internet, about which of these approaches, is better. And fortunately, at the moment we don't have any evidence for one, above the other.

The other problem with, surgery is of course, it carries risks.

• You have to have a general anesthetic
• Then there's a risk of complications at the time of surgery
• The surgery itself can even put patients at risk of developing, chronic post, surgical pain.

The other problem is that surgery, isn’t  a cure for endometriosis, around 30% of patients experience no benefit. And then their high recurrence rates of up to 50%, within five years.

Hormone treatments

What about, hormone treatments for Endometriosis?

Well, there are range of different hormone treatments that can be used. And these includes combined contraceptives, progestin and GnRH agonists and antagonists. And they can be given by a range of different approaches.

But:

• There isn't one particular hormone that said to be more effective than the other.
• They're only effective when they're being taken.
• They all have a range of different, side effects.
• They’re all contraceptive.

And this is often a young population of women who are maybe wanting to have a family and don't want to take something which is not, fertility sparing.

We carried out a survey of patients across the UK, just over, 1500 patients, responded to this survey asking them about these hormone treatments. And this is the word cloud from the question that we asked them: which hormone or medication helped most. And you can see that whilst there is a large number of different, treatments, there isn't one treatment that comes to the fore. And in fact, the evidence would suggest that current hormone treatment leaves about 50% of patients with persistent or recurrent pain.

Self-management and diet

So it's perhaps not surprising that, patients, turn to other treatment strategies, strategy self-management strategies, such as changing their diet.

And we carried out another survey just three years ago now of just under 3000 individuals with Endometriosis across the globe. And you can see that they use a different, number of approaches, in terms of removing things from their diet, perhaps not surprisingly, things like alcohol and, caffeine, processed sugar, ultra processed foods.

And you can see that and these approaches did appear to have an impact upon reducing some of their painful symptoms.

Gut microbiome research

And so, perhaps not surprisingly, there has been a move to look, at gut bacteria in the microbiome. and endometriosis.

So if we look at what, studies have been performed to date, first of all, focusing on animal studies, most of these studies, have used models of induced endometriosis. And this is largely because, mice, for example, the commonest animal that is studied don't actually spontaneously develop Endometriosis, says they don't menstruate. So you have to develop a model of mouse menstruation and then, using that model and induce endometriosis.

The other problem with these studies is:

• They focus largely on disease development and not symptom relief.
• They also use a wide number of different approaches.
• So there's little consistency.
• Whilst there have been some promising, treatments suggested, the studies supporting these have lacked measures of well-being or behavior.

If we look at the human studies, looking at the gut microbiome, there have only been a small number of studies to date, and most of them have involved only small numbers of patients. So they're difficult to generalize.

And again, like the animal studies, they've used a multitude of different, approaches. And whilst there are, larger studies emerging, we don't have a consistent, if you like, endometriosis microbiome pattern as yet.

ENDO 1000 study

But I think things are changing. And one of the studies that we're leading on, in Edinburgh hopes to address this. And this is called the ENDO 1000 study. You can scan the QR codes here if you want to hear a bit more about it and follow the the study on social media.

And with this study, what we're hoping to do is, a recruit a thousand people with endometriosis associate symptoms. And we launched this study. I'm just in January this year. And then we're going to work with them really closely over a period of two years.

They'll record:

• Their symptoms
• Any treatments that they have
• Any changes in their health on our Endo1000 app.

And at the same time, we'll collect, biological samples:

• Saliva to look at their genetics
• Blood to look at their inflammatory profile
• Urine, feces and a vaginal swab to look at their microbiome and their metabolome.

And the idea is that we'll collate all of the information that we collect from the app, from interrogation of these bio samples with data that we'll also collect from a smartwatch, looking at their activity and sleep patterns into this big, resource that we can interrogate to look for patterns that might help, with, another noninvasive, diagnosis, test for endometriosis.

But I think, most importantly, help us identify patterns which can predict the best medical and surgical, and self-management strategies for the condition.

Question n°1

Endometriosis can take years to be diagnosed, but for women, what are the key warning signs that people should look out for?

Expert's answer

So I think one of them is in particular that you've just mentioned is that kind of normalization of pain. So if you have painful symptoms that are interfering with your ability to work or to socialize, it's really important you seek help. In terms of symptoms which might make you think it’s endometriosis: symptoms that have a cyclical pattern so there may be related to the menstrual cycle that can be, a warning sign.

Question n°2

How can someone understand which option might fit them best?

Expert's answer

So it's slightly depends which symptoms are important to them and what point they are in their life course. So if pain is a primary symptom, then they might go for surgery or some hormone treatments. But of course if fertility is an issue for them. Surgery can be helpful for some types of endometriosis, but often patients have to undergo IVF. I'm always very positive about that aspect of the disease if someone is given a first diagnosis, because we have to emphasize that two thirds of people will conceive spontaneously, without any support, if they happen to have endometriosis. So the one third often undergo IVF treatment, which of course is a big undertaking that IVF treatments and patients with endometriosis is generally very successful. So there’s hope.

Question n°3

In your opinion, what would be the next step in research?

Expert's answer

So I think it's it's about, performing these bigger studies a bit a bit like ENDO 1000, to try and actually define the endometriosis microbiome pattern and then obviously look at that pattern. And that pattern might be used, as I say in in diagnosis. But I think more importantly potentially to alleviate the symptoms associated with the condition.


Question n°4

Symptoms sometimes overlap with IBS. In your opinion, could the microbiome be part of the link between the two conditions ?

Expert's answer

Yes. I mean, around 20 to 40% of patients who have an endometriosis diagnosis will also have, irritable bowel syndrome. So there's definitely a link there. And I think the gut microbiome is the most natural place to to look for that link.

_{1. Dubli K, Balasundaram P, Chaudhari R et al Exploring the Impact of Skin Care Routines on the Skin Microbiome and Possible Skin Disease Risk-A Pilot Study. Biomedicines. 2025 Sep 27;13(10):2371.}

_{2. GBD 2021 diseases and injuries collaborators. Global incidence, prevalence, years lived with disability (YLDS), disability-adjusted life-years (DALYS), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the global burden of disease study 2021. Lancet. 2024;403(10440):2133–2161.}

_{3. https://apps.who.int/gb/ebwha/pdf_files/EB156/B156_(24)-fr.pdf}

_{1. Mimpen IL, Battaglia TW, Parra-Martinez M et al. Microbial Metabolic Pathways Guide Response to Immune Checkpoint Blockade Therapy. Cancer Discov. 2026 Jan 12;16(1):95-113.}

_{2. https://www.who.int/news-room/fact-sheets/detail/cancer}

More than a quarter (25%) of stools are classified as severe constipation (hard, difficult-to-pass lumps) or mild to moderate constipation (lumpy, sausage-shaped stools), and less than a quarter (25%) as mild diarrhea (fluffy pieces with ragged edges, a mushy stool) or severe diarrhea (watery stools with no solid pieces).

More than a quarter (25%) of stools are classified as mild diarrhea (fluffy pieces with ragged edges, a mushy stool) or severe diarrhea (watery stools with no solid pieces), and less than a quarter (25%) as severe constipation (hard, difficult-to-pass lumps) or mild to moderate constipation (lumpy, sausage-shaped stools).

More than a quarter (25%) of stools are classified as severe constipation (hard, difficult-to-pass lumps) or mild to moderate constipation (lumpy, sausage-shaped stools), and more than a quarter (25%) as mild diarrhea (fluffy pieces with ragged edges, a mushy stool) or severe diarrhea (watery stools with no solid pieces).

Patients who meet diagnostic criteria for IBS but whose bowel habits cannot be accurately categorized into one of the three groups above.

^{1. Vermeijden NK, de Silva L, Manathunga S, et al Epidemiology of Pediatric Functional Abdominal Pain Disorders: A Meta-Analysis. Pediatrics. 2025 Feb 1;155(2):e2024067677. doi: 10.1542/peds.2024-067677.} 

^{2. Devanarayana NM, Rajindrajith S. Irritable bowel syndrome in children: Current knowledge, challenges and opportunities. World J Gastroenterol. 2018 Jun 7;24(21):2211-2235. doi: 10.3748/wjg.v24.i21.2211.} 

^{3. Rome Foundation. Appendix A: Rome IV Diagnostic Criteria for FGIDs. Available from: https://theromefoundation.org/rome-iv/rome-iv-criteria/. [Last concult: 2026 Jan 20]}

^{4. Romano C, Ferrau' V, Cavataio F, Iacono G, Spina M, Lionetti E, Comisi F, Famiani A, Comito D. Lactobacillus reuteri in children with functional abdominal pain (FAP). J Paediatr Child Health. 2014 Oct;50(10):E68-71. doi: 10.1111/j.1440-1754.2010.01797.x.} 

^{5. Kianifar H, Jafari SA, Kiani M, et al. Probiotic for irritable bowel syndrome in pediatric patients: a randomized controlled clinical trial. Electron Physician. 2015 Sep 16;7(5):1255-60. doi: 10.14661/1255.}

^{6. Vernon-Roberts A, Alexander I, Day AS. Systematic Review of Pediatric Functional Gastrointestinal Disorders (Rome IV Criteria). J Clin Med. 2021 Oct 29;10(21):5087. doi: 10.3390/jcm10215087.}

^{7. Vermeijden NK, de Silva L, Manathunga S, Spoolder D, Korterink J, Vlieger A, Rajindrajith S, Benninga M. Epidemiology of Pediatric Functional Abdominal Pain Disorders: A Meta-Analysis. Pediatrics. 2025 Feb 1;155(2):e2024067677. doi: 10.1542/peds.2024-067677.}

^{8. Di Nardo G, Barbara G, et al. Italian guidelines for the management of irritable bowel syndrome in children and adolescents : Joint Consensus from the Italian Societies of: Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP), Pediatrics (SIP), Gastroenterology and Endoscopy (SIGE) and Neurogastroenterology and Motility (SINGEM). Ital J Pediatr. 2024 Mar 14;50(1):51. doi: 10.1186/s13052-024-01607-y.}

^{9. Gordon M, Sinopoulou V, Tabbers M et al. Psychosocial Interventions for the Treatment of Functional Abdominal Pain Disorders in Children: A Systematic Review and Meta-analysis. JAMA Pediatr. 2022 Jun 1;176(6):560-568. doi: 10.1001/jamapediatrics.2022.0313.} 

^{10. Saulnier DM, Riehle K, Mistretta TA et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011 Nov;141(5):1782-91. doi: 10.1053/j.gastro.2011.06.072.}

^{11. Hollister EB, Oezguen N, Chumpitazi BP, et al. (2019). Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome. J Mol Diagn. 2019 May;21(3):449-461. doi: 10.1016/j.jmoldx.2019.01.006.}

^{12. Baştürk A, Artan R, Yılmaz A. Efficacy of synbiotic, probiotic, and prebiotic treatments for irritable bowel syndrome in children: A randomized controlled trial. Turk J Gastroenterol. 2016 Sep;27(5):439-443. doi: 10.5152/tjg.2016.16301.} 

^{13. Groen J, Gordon M, Chogle A, et al. ESPGHAN/NASPGHAN guidelines for treatment of irritable bowel syndrome and functional abdominal pain-not otherwise specified in children aged 4–18 years. J Pediatr Gastroenterol Nutr. 2025 Aug;81(2):442-471. doi:10.1002/jpn3.70070.}

^{14. Rutten JMTM, Vlieger AM, Frankenhuis C et al. Home-Based Hypnotherapy Self-exercises vs Individual Hypnotherapy With a Therapist for Treatment of Pediatric Irritable Bowel Syndrome, Functional Abdominal Pain, or Functional Abdominal Pain Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2017 May 1;171(5):470-477. doi: 10.1001/jamapediatrics.2017.0091.}

_{1. WHO}

_{2. Pang MD, Kjølbæk L, Bastings JJAJ, et al. Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study. Nat Metab. 2025 Oct;7(10):2083-2098.}

_{3. WHO}

_{4. Vidal}

_{1. WHO}

_{2. Pang MD, Kjølbæk L, Bastings JJAJ, et al. Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study. Nat Metab. 2025 Oct;7(10):2083-2098.}

_{3. SIAL}

_{^{1. Mountain KE, MacIntyre DA, Lee YS et al. ABO blood group antigens influence host-microbe interactions and risk of early spontaneous preterm birth. NPJ Biofilms Microbiomes. 2025 Sep 10;11(1):170.}}

_{^{2. https://www.who.int/news-room/fact-sheets/detail/preterm-birth}}

_{1. https://www.orpha.net/en/disease/detail/99977}

_{2. Liang L, Mai S, Sethi G et al. Fungal microbiota signatures anticipate neoadjuvant immunochemotherapy outcomes in esophageal cancer. J Immunother Cancer. 2025 Oct 8;13(10):e011508.}

_{1. Li C, Wang H, Lin X et al. Chronic alcohol consumption disrupts the integrity of the blood-brain barrier through the gut-brain axis. Commun Biol. 2025 Nov 25.}

_{2. https://bestpractice.bmj.com/topics/en-gb/198}

_{3. https://www.who.int/fr/news-room/fact-sheets/detail/alcohol}

_{1. https://bestpractice.bmj.com/topics/en-gb/198}

_{2. https://www.who.int/fr/news-room/fact-sheets/detail/alcohol}

_{3. Li C, Wang H, Lin X et al. Chronic alcohol consumption disrupts the integrity of the blood-brain barrier through the gut-brain axis. Commun Biol. 2025 Nov 25.}