Microbiota imbalance at age one predicts allergies at age five

Canadian researchers 1 are using the stools of one-year-olds to identify microbial communities that can predict subsequent allergies. Their aim is to one day change the course of things via the gut microbiota.

The skin microbiota The ENT microbiota Asthma and microbiota Allergic rhinitis Food allergies

On their fifth birthday, some of the thousands of Canadian children participating in the vast (sidenote: https://childstudy.ca/ ) study, which has followed these children since birth, were diagnosed with allergies such as:

Since their medical records and stool samples collected at three months and one year were carefully preserved as part of the study, the researchers were able to investigate whether there were any warning signs. As it turns out, there appears to be one warning sign universal to all four allergies: the gut microbiota.

Delayed diversity and dysbiosis

Asthma, eczema, food allergies, and hay fever – whatever the allergy –, all future allergy sufferers had a gut microbiota that was insufficiently diversified at age one, as if they were much younger than their birth certs suggested. In addition to this lack of maturity, the microbiota of the future allergy sufferers presented a dysbiosis: four beneficial bacterial species were depleted, while five species generally considered pathogenic were present in excess.

Suspected mechanisms

This early imbalance may explain the lower production of beneficial (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. 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. ) and the overproduction of inflammatory molecules. In turn, this leads to the subsequent development of allergies... but also gives hope of one day reversing these allergies by correcting gut dysbiosis. 

"Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime." 2

Dr Turvey, co-director of CHILD and co-author of the study

Not everyone is equal when it comes to allergies

In the meantime, bear in mind another result of the study: when it comes to allergies, our children are not all equal. Boys are more affected, as are children whose fathers and/or mothers suffer from allergies, and those who were prescribed antibiotics before age one. Conversely, breastfeeding up to six months protects against allergies, as does Caucasian ethnicity. While screening the origin or health record of any future spouse may be out of the question, breastfeeding should be encouraged and antibiotics used with the utmost care and only on prescription.

Antibiotics: what impact on the microbiota and on our health?

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The Institute's Team

Biocodex Microbiota Institute: who are we ?

200+ professionals

More than 230 researchers and healthcare professionals across diverse disciplines have been collaborating with the Biocodex Microbiota Institute since its creation in 2017. All together, we join forces and skills to advance microbiota research (gut microbiota but also vaginal, skin, lung…) and raise awareness about its crucial role.

At Biocodex headquarters, the Institute is a team of 7 professionals in science, communications, digital, social networks, etc. with complementary profiles, all experts in their fields. Discover them!

Biographies of the Biocodex Microbiota Institute's team

Olivier Valcke

Corporate Scientific Communication Director

Former journalist, with 15 years of experience in health communication, Olivier coordinates all of the Institute's activities and oversees the microbiota team. He is specifically responsible for press and public relations of the Biocodex Microbiota Institute.

Fan of rugby and French literature (yes the two are compatible!), this natural-born storyteller turns complex scientific concepts into simple words.

His mission? Making microbiota science accessible to everyone and turn the Institute as a « media reflex » when it comes to microbiota.

Follow Olivier on Linkedin

Naouel Ait Meddour

Global Social Media Manager

The solution provider, always optimistic & no short of ideas, her motto: “there are no failures, only lessons to be learned”.

She has worked in a variety of professional field, jumping from finance to real estate and find her way in the healthcare area. She is the Social Media Manager, working on the Social Media strategy to create a strong microbiota community.

For her, Microbiota is an essential player for a better health.

Follow Naouel on Linkedin

 

Mathilde Baissac

International Digital Manager

She is the guardian of the Institute's digital ecosystem. With 7 years of experience in Digital Marketing, she ensures that the site is well referenced, always evolving, and pampers our online communities. She oversees the creation and monitoring of KPIs, so that the whole team can steer the Institute in the best possible direction. Her motto: “Look at the sun, the shadow will be behind you”. She is organized, optimistic and often has a powerful/crazy idea up her sleeve.

For her, Microbiota is THE future of healthcare.

Follow Mathilde on Linkedin

 

Émilie Fargier

Scientific and Medical Communication Manager

With a deep-rooted passion for science and over 17 years of experience, Emilie holds a PhD in microbiology. Her journey has transitioned from academic research to industrial research within the pharmaceutical industry. Outside of her scientific endeavors, Emilie is an avid yoga practitioner and has a fervent passion for science fiction and fantasy literature.

As the team's microbiome science explorer, she ensures the scientific veracity of the Biocodex Microbiota Institute's content. Known for her curiosity and ability to demystify complex scientific concepts, her motto, "Unlocking the microbial mysteries for global well-being," reflects her dedication to enhancing health through the power of the microbiota.

Follow Émilie on Linkedin

 

Élodie Mintet

Scientific and Medical Communication Manager

The Scientific Guardian of the Institute. Her motto "Science must be accessible to everyone". With 10 years of experience in academic research within healthcare and scientific valorization in the industry, Elodie has developed a strong consumer-oriented approach.  Passionate and curious, she transforms research related to the microbiota into engaging and informative content for the general public.

For her, Microbiota is a global health solution and a game changer regarding personalized treatments.

 

Clémence Enou

Coordinator of the Global Microbiota Scientific Communication Team

News here and there, every week brings new updates just for you, and in all languages – made possible in part thanks to Clémence. Her calmness inspires confidence and prevents stress during rush times.

Her motto: 'Choose a job you love, and you won't have to work a single day in your life!' This is what she has chosen by balancing these two professions at the Microbiota Institute and in her practice as a Naturopath.

For her, Microbiota is the key to all the answers that science is waiting for. It still requires patience for it to reveal its secrets. In the meantime, taking care of it is essential!

 

Amina Khribech

Digital Marketing Apprentice

After an initial career in the sciences, Amina, now a work-study student in commerce, management and marketing, has returned to her first vocation: digital marketing.

At the Institute, she has found the perfect balance between her scientific interests and her digital communication skills. In particular, she is responsible for implementing content on the Institute's website, managing site updates, and managing the monthly newsletter for healthcare professionals and the general public. And when she has a little time left over, she contributes to the creation of videos for the Institute.

Joining the Biocodex Microbiota Institute gives her the opportunity to contribute to the promotion of this essential health organ.  

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A bacterium that prevents diabetes mellitus?

For the time being, this dream has only been validated in test tubes and in mice, not yet in humans. However, the A. indistinctus bacterium may improve insulin resistance in people with pre-diabetes.

The gut microbiota Type 2 diabetes

(sidenote: Diabetes mellitus Chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Over time, diabetes can damage blood vessels in the heart, eyes, kidneys and nerves. ) is all about sugar, and more specifically, blood sugar levels ( (sidenote: Glycemia Blood sugar level. ) ). The aim is to avoid peaks (i.e., hyperglycemia) following meals. In healthy individuals, (sidenote: Insulin Hormone produced by the pancreas tasked with lowering blood sugar levels to around 1 g/L.  ) regulates blood sugar levels at around 1 g/L. In diabetic patients, the body fails in this regard, either because the pancreas does not produce enough insulin (type I diabetes mellitus), or because the body resists insulin’s commands (type II diabetes mellitus). The gut microbiota appears to be involved in the insulin resistance observed in type II diabetes, but the mechanisms involved remain unclear. Or rather “remained” unclear, since a study published in the prestigious journal Nature has shed some light on the subject.

Micro-sugars promote insulin resistance

The researchers concluded that the richer our stools are in certain molecules, the greater our resistance to insulin. The feces of insulin-resistant volunteers contained far more (sidenote: Carbohydrates A family of macronutrients that includes sugars (i.e., simple carbohydrates), which often have a sweet taste and include glucose, fructose, galactose, maltose, lactose, and sucrose; and starches (i.e., complex carbohydrates). ) , particularly tiny (sidenote: Sugars Fructose, galactose, mannose and xylose. ) produced by bacteria. These micro-sugars are far from harmless. They promote fat accumulation, stimulate our immune system to the point of causing inflammation (admittedly mild, but prolonged and harmful), and ultimately lead to insulin resistance.

2 million deaths related to diabetes mellitus (1.5 million) and diabetes-related kidney disease (0.5 million) in 2019.

422 million diabetic patients in 2014, compared with 108 million in 1980.

+3% Between 2000 and 2019, there was a 3% increase in diabetes mortality rates by age.

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The bacteria involved

Two types of bacteria seem to be involved:

  • bacteria of the Lachnospiraceae family, which are associated with a higher production of these tiny sugars and insulin resistance; and
  • Bacteroidales (Bacteroides, Alistipes, and Flavonifractor), which reduce levels of these sugars and insulin resistance.

A direct effect of the “friendly” Bacteroidales has even been measured in test tubes, where they devour the micro-sugars. The most gluttonous? The bacterial species Alistipes indistinctus consumes the widest variety of micro-sugars. It also works in obese mice, where a pinch of A. indistinctus lowers the amount of micro-sugars in mice’s stools, lowers blood sugar levels, and makes the mice more sensitive to insulin. 

Although human trials are clearly essential before any recommendations can be made, these findings have two main implications:

• Lachnospiraceae may be a biomarker of pre-diabetes; and

• the probiotic A. indistinctus may improve insulin sensitivity in pre-diabetic individuals.

The gut microbiota

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Valued Partnerships

Since its creation, the Biocodex Microbiota Institute has forged strong partnerships with patient associations, learned societies and public health organizations. Together, we pursue a common goal: to inform, educate and raise awareness of the importance of the microbiota to our health.

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Can antibiotics promote the growth of harmful bacteria in the gut?

Antibiotics are lifesavers, but they can also have unexpected consequences. A new research shows how antibiotics can promote the growth of harmful bacteria in the gut and points the way to new treatments.

Antibiotic resistance is a pressing global public health concern that resulted in 1.27 million deaths worldwide in 2019 1. One approach to prevent these infections, particularly Carbapenem-resistant Enterobacteriaceae (CRE), is to understand what drives the colonization of the intestine by these bacteria.

Your gut is home to a diverse community of beneficial bacteria that help prevent harmful pathogens like CRE from taking hold. Healthy gut bacteria have mechanisms to prevent the colonization of pathogens, such as production of beneficial molecules, also called metabolites, like (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. 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. ) ). Broad-spectrum antibiotics disrupt these mechanisms and promote the growth of antibiotic-resistant bacteria.

40%–50% CRE infections are associated with mortality rates as high as 40%–50%

Antimicrobial resistance: a global threat, an international response

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The yin-yang effect!

Are Broad-spectrum antibiotics responsible for increased risk of infection with CRE? Yes, according to the 2023 study published in Nature Communication by a researcher from Imperial College London 2.

Eight broad-spectrum antibiotics were tested on faecal samples from healthy human donors:

  • meropenem
  • imipenem/cilastatin
  • ertapenem
  • piperacillin/tazobactam
  • ciprofloxacin
  • ceftriaxone
  • ceftazidime
  • and cefotaxime

These antibiotics are known to promote susceptibility to CRE intestinal colonisation. The researchers used a specific growth medium to measure: 1) the impact of the antibiotics on the abundance of gut commensal taxa from the faecal microbiota, 2) nutrients and microbial metabolites concentration in the faecal cultures.

The study showed that broad-spectrum antibiotics, often used to treat infections, can disrupt the balance of your gut microbiota. They reduce the population of beneficial bacteria (including Bifidobacteriaceae and Bacteroidales), making it easier for CRE to flourish.

What was even more interesting is that when piperacillin/tazobactam were tested in a mouse model, these antibiotics not only affected the bacteria but also altered the environment in gut. They increased the availability of certain nutrients, like amino acids, that support the growth of CRE. This nutrient-rich environment becomes a breeding ground for the resistant bacteria.

On the flip side, these antibiotics decreased the concentration of microbial metabolites, such as butyrate or propionate, some of which inhibit the growth of CRE. When these metabolites are depleted, CRE has fewer obstacles in its path.

Antibiotic resistance

Antibiotic resistance is a major global threat, and the emergence of formidable pathogens CRE poses a serious challenge to public health. Understanding the role of the gut microbiota in antibiotic resistance is paramount.

Short-chain fatty acids (SCFAs) are key metabolites produced by beneficial gut bacteria that act as guardians of gut health. However, the indiscriminate use of broad-spectrum antibiotics can disrupt the gut microbiota, leading to a decrease in SCFA production and an increase in the growth of antibiotic-resistant bacteria.

As medical professionals, we must be aware of the intricate interactions within the gut microbiota. By carefully considering the impact of antibiotics on the delicate balance of the microbiota, we can take a step closer to combatting antibiotic resistance effectively and preserving the health of our patients. 

What is the World AMR Awareness Week?

Each year since 2015, the WHO organizes the World AMR Awareness Week (WAAW), which aims to increase awareness of global antimicrobial resistance.

Held on 18-24 November, this campaign encourages the general public, healthcare professionals and decision-makers to use antimicrobials carefully to prevent the further emergence of antimicrobial resistance.

Recommended by our community

"Congratulations on the wonderful medical profession"  -@PhucTra01451784 (From Biocodex Microbiota Institute on X)

"I salute your efforts"  -@EmmanuelMedical (From Biocodex Microbiota Institute on X)

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News General Medicine Gastroenterology Pediatrics Off

Fecal transplant: “where, when, how much” needed to optimize effects on IBS?

What is the best combination of factors for fecal transplantation as a treatment for irritable bowel syndrome (IBS)? According to Norwegian researchers and clinicians, a transplant dose of between 60 g and 90 g into the small intestine, rather than the colon, and ideally repeated.

IBS

44% Only 2 out of 5 people said their doctor had informed them of the appropriate behaviors to adopt to preserve their microbiota balance

Between 2015 and 2020, fecal microbiota transplant (FMT) as a treatment for irritable bowel syndrome (IBS) was tested in seven randomized controlled trials (RCTs). The outcomes of these RCTs varied considerably, probably due to differences in the protocols used. A Norwegian team studied the effects of FMT dose, repetition, and area of administration, using the same protocol as in their previous RCT, which saw very good results (long-standing effects up to three years after FMT, with only a few mild adverse effects). The transplant came from the same (sidenote: Super-donor A donor with high microbial diversity, whose microbiota quality conditions FMT results. In this case, a healthy, non-smoking 40-year-old Caucasian male born vaginally, breastfed, who had taken only a few courses of antibiotics during his life, took no medication regularly, had a normal BMI, exercised regularly, and took sport-specific dietary supplements (which made his diet richer than average in protein, fiber, minerals, and vitamins). ) .

Symptoms improved with repeated FMT

This new study included 186 patients suffering from irritable bowel syndrome, randomized into three groups receiving a 90 g fecal transplant (versus 30 g or 60 g in the previous RCT) either to the colon, to the duodenum, or twice to the duodenum with a one-week interval.

In the year following the FMT, the researchers observed a much lower prevalence of (sidenote: Assessed using the IBS-SSS, the Birmingham IBS Symptom Questionnaire (BSQ) and the Fatigue Assessment Scale (FAS). ) , regardless of the group and the time elapsed since FMT: present in 75% of patients on the day of transplantation, they affected 17%-32% (depending on the group) after 3 months, and 24%-41% after one year. Similarly, (sidenote: Assessed using the IBS Quality of Life Instrument (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaire. ) improved in all three groups, regardless of the time elapsed since FMT. Moreover, repeating transplantation improved the beneficial effects on symptoms and quality of life.

Your IBS Diagnosis Check List

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Favoring the small intestine over the colon

An analysis of fecal samples (16s rRNA) taken at baseline and at 3, 6, and 12 months after FMT showed a significant reduction in dysbiosis in all treatment groups. Bacterial profiles changed considerably following FMT for all three groups and at all observation dates, with differences between the groups. These changes notably concerned six bacteria linked to symptoms and fatigue, such as Alistipes spp., implicated in several diseases such as depression, anxiety, and chronic fatigue syndrome, or Holdemanella biformis, which has anti-inflammatory effects.

Transplanting into the small intestine enables the colonization of beneficial bacteria over the long term, unlike transplanting into the colon, where the effect appears to be more transient. Conversely, while the beneficial effect increased with dose in the previous RCT (greater effect at 60 g than at 30 g), the 90 g dose has no additional benefit compared with the 60 g already tested: the optimal dose would therefore be between 60 g and 90 g.

Explain fecal transplantation to your patients with this dedicated content: 

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Microbiota: essential to health, but limited global awareness

What do our fellow citizens know today about the role of microbiota? What do they know about how to take care of their microbiota? What role do healthcare professionals play in informing patients? To answer these questions, the Biocodex Microbiota Institute commissioned Ipsos to conduct a major international survey on the subject: the International Microbiota Observatory. To carry out this survey, Ipsos questioned 6,500 people in 7 countries1 . The survey was conducted from March 21 to April 7, 2023. The results were presented on June 27, World Microbiome Day.

Very little knowledge of the word “microbiota”

As a general rule, knowledge of microbiota is fairly low: only 1 in 5 people say they know the exact meaning of the term microbiota (21%), while the rest admit to knowing the term by name only (43%). More than 1 in 3 people say they’ve never even heard of the word (36%). Moreover, when we dig deeper into their level of knowledge, the notions are superficial. While a small majority claim to know the intestinal microbiota (53%, but only 24% know exactly what it is), other types of microbiota are much less well known: whether it’s vaginal microbiota (45% of interviewees know the term, but only 18% know exactly what it is), oral microbiota (43% know it by name, but 17% know what it is) or skin microbiota (40% know the term, but only 15% know what it is). Others are even less well known, such as urinary microbiota (only 14% know exactly what it is), pulmonary microbiota (13% know exactly what it is) and ENT microbiota (11% know exactly what it is).

And relatively poor knowledge of the role and importance of microbiota

Around 3 out of 4 interviewees are aware that a risk of microbiota imbalance can have major consequences for health (75%), that our diet has major consequences on the balance of our microbiota (74%) and that our microbiota play a real role in immune defense mechanisms (72%). For the rest, knowledge remains very moderate. More than 1 in 3 people are unaware that antibiotics have an impact on our microbiota (34%). Nearly 1 in 2 people are unaware that microbiota are made up of bacteria, fungi and viruses (46%), and that they enable the gut to deliver essential health information to the brain (47%). 1 in 2 people think that when our microbiota is unbalanced or malfunctioning, there’s not much we can do about it (47%). Finally, the vast majority of those interviewed were unaware that many diseases, such as Parkinson’s, Alzheimer’s and autism, could be linked to microbiota (75%).

1 in 5 people know what the word microbiota means (21%)

24% said they know exactly what gut microbiota is

1 in 3 people have been informed by a healthcare professional that antibiotics can upset the microbiota balance (33%)

The beginning of awareness?

More than 1 in 2 people today say they have adopted behaviors in their daily lives to maintain the balance of their microbiota (57%). This new awareness is to be applauded, but it should also be put into perspective. Firstly, because only 1 in 7 people say they do this “a lot” (15%), while most of the others say they do it only “a little” (42%). Secondly, 43% of those questioned said they had not adopted any specific behavior. The results of the International Microbiota Observatory show that there’s still a lot to be done in this area.

Information provided by healthcare professionals: a game-changing vector of information!

Fewer than 1 in 2 patients say that their doctor has ever explained to them how to maintain balanced microbiota (44%, but only 19% have had this explained to them more than once), or prescribed probiotics or prebiotics (46%, but only 21% say they have done so several times). Only a minority of those interviewed claim to have been made aware by their doctor of the importance of having a well-balanced microbiota (42%). Finally, only 1 in 3 said their doctor had ever taught them what microbiota was and what it was used for (37%, and only 15% had had this explained to them several times).

The information provided by doctors when prescribing antibiotics illustrates just how inadequate it still is to make patients aware of the risks of treatment in terms of microbiota imbalance. Prescribing antibiotics should be an opportunity to provide essential information on the microbiota, but in many cases it isn’t. When prescribing antibiotics, for example, the patient’s microbiota is at risk. When antibiotics are prescribed, less than 1 in 2 patients say that their doctor has informed them of the risk of digestive problems associated with antibiotics (41%). Only 1 in 3 were given advice on how to minimize the negative consequences of taking antibiotics on their microbiota (34%) or informed that taking antibiotics could have negative consequences on the balance of their microbiota (33%).

What the survey shows is that once a patient has received all the information on the subject, and repeatedly, his or her relationship with microbiota changes significantly, and stands out from the average. More than 9 out of 10 people (95%) who have received repeated information from their healthcare professional have adopted behaviors to keep their microbiota balanced, compared with 57% of all those surveyed. Repeated information from a healthcare professional therefore has a very strong impact on knowledge levels and behaviors.

This exclusive survey reveals both a general lack of understanding of how the microbiota affects our health and the essential role of healthcare professionals in imparting knowledge.

1 in 2 patients say that their doctor has ever explained to them how to maintain balanced microbiota

95% of people having received information repeatedly from their healthcare professional have adopted behaviors to limit the risk of microbiota imbalance

vs 57% Overall

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Article Gut microbiota

The impact of gravity on irritable bowel syndrome

By Dr. Maria Teresa Galiano
Gastroenterology and Endoscopy Service, Servimed, Bogota, Colombia

In a recent paper [1], it has been suggested that IBS may result from ineffective anatomical, physiological, and neuropsychological gravity management systems designed to optimize gastrointestinal form and function, protect somatic and visceral integrity, and maximize survival in a gravity-bound world.

Could you comment on this hypothesis with your clinical point of view?

This hypothesis is very interesting. I think it can be considered among the multiple hypotheses that seek to explain irritable bowel syndrome. However, it must be tested. Studies must be conducted to prove that physical alterations due to the changes in gravity affect gastroenterological physiology. I think it may be true that gravity affects an organism’s physiology and that we are usually in balance with this permanent force to which humans and all living things on Earth are subjected. The consequences arising when this equilibrium is altered can include IBS.

Do you agree with the author explaining that consequences of gravity result in gut microbiota alteration?

I agree with the author that gravity can alter gut microbiota and that it can also alter its functioning, including fermentation. I think it can also alter the volume of gas that acts upon the bowel wall. This also must be tested in the corresponding studies, but I agree with the author’s point regarding gut microbiota’s susceptibility to gravity.

Would you share this hypothesis with your patients?

I would share this hypothesis with patients to whom I believe this hypothesis may apply based on their physiopathology and as a possible explanation for their symptoms. As a matter of fact, I see in changes in my patients when they travel to places that are at sea-level and come back to Bogota where I live. Bogota is located 2,600 meters above sea-level. When these patients return to Bogota, they exhibit more symptoms because of changes in barometric pressure. Changes in barometric pressure cause changes in sensation, distension, and gas in the bowels. On many occasions, I explain their symptomatology based on the changes in their physiology that result from the different altitudes that they experience. The changes that occur due to variations in the equilibrium with the force of gravity could be used to explain these patients’ symptoms.

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Expert opinion Irritable bowel syndrome

Vaginal Microbiota #19

By Pr. Satu Pekkala
Academy of Finland Research Fellow, Faculty of Sport and Health Sciences, University of Jyväskylä, Finland

Cervical cancer: the walls are closing in on Lactobacillus iners

Shi W, Zhu H, Yuan L, et al. Vaginal microbiota and HPV clearance: A longitudinal study. Front Oncol 2022; 12: 955150.

High-risk human papillomavirus (HRHPV) is the leading cause of cervical cancer. Sexual activity, smoking, and oral contraception are among the many factors that influence initial infection, the resolution or the onset of HR-HPV, and potential progression to cancer. In recent years, the vaginal microbiota has been added to this list. The value of this study is therefore clear, since it monitored the cervical microbiota of HR-HPV infected Chinese women presenting histologically confirmed, and mostly low-grade, cervical lesions. A 16S rRNA analysis of the microbiota of the 73 participants in the study (aged between 24 and 68 years) showed that HPV had disappeared in 45 of the women (61.6%) by the end of the twelve-month study period. The clearance or otherwise of the virus was not due to differences in the patients’ age, the stage of the disease, the HPV subtype, the type of vaginal bacterial community, or vaginal microbiota diversity. Instead, certain bacterial species seem to be involved: women depleted in enterococcus ASV_62 and enriched in Lactobacillus iners at baseline were less likely to have HPVHR clearance at month twelve. The only exception was 22 women who underwent surgical treatment (conization) for highgrade lesions, perhaps because the immediate impact of lesion resection on HPV clearance masked the impact of the flora. A possible link between L. iners and HR-HPV had previously been reported by a meta-analysis suggesting a two- or even three-fold higher risk of persistent HR-HPV when the vaginal microbiota is dominated by L. iners. This bacterium appears to be both flexible and adaptable, dominating the vaginal microbiota of certain women during menstruation or episodes of bacterial vaginosis. On the other hand, a vaginal microbiota dominated by L. iners (CST III) is frequently reported as one of the most common types of vaginal bacterial community among Asian child-bearing age women. Therefore, it is not yet clear from the current literature whether this particular strain of Lactobacillus should be considered beneficial, pathogenic, or both. Further work is also needed to clarify the mechanisms by which L. iners promotes persistent HPV infection or lesion progression, especially since the current study involved a small number of patients.

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