From the moment we are born, the small world around us contributes to the unique composition of our microbiota. The microbes we are exposed to differ depending on whether we are born via c-section, are breastfed, grow up on a farm, have a dog... or have brothers and sisters! To assess the impact of siblings on the development of the microbiota, the researchers analyzed the composition of the gut flora (from 1 week to 6 years of age) and pharyngeal microbiota (from 1 week to 3 months of age) of nearly 700 children. The samples were regularly renewed, with nearly 4,500 samples sequenced in all. At each stage, the researchers took into account the child’s family situation, i.e. only child or presence of older/younger sibling(s). They also noted about 15 additional factors that may influence a child’s microbiota, from birth weight to household income. Lastly, they compared the data collected from the children with the presence of asthma, allergic rhinitis, and sensitization to various allergens at age six.

Microorganisms in microbiota have family spirit 

The researchers found that having siblings during early childhood was one of the most important determinants of the composition of the gut microbiota and airway microbiota. This effect was most pronounced in children in their first year of life with older siblings. Their gut microbiota was richer, more diverse, and more mature than that of only children. Furthermore, a large family is not necessary, since having one older sibling close in age mattered more than having a number of siblings. The consolation for only children: the difference between their microbiota and that of children with siblings subsides by age four.

Influence of siblings on infants’ respiratory microbiota greater than that of breastfeeding

What about the airway microbiota? During the first three months of life, it too was modified to a greater extent by the presence of a sibling than by other major factors, such as breastfeeding or antibiotic use. The microbiota of babies with siblings was less diversified than that of babies with no siblings. However, unlike the gut microbiota, lower bacterial diversity in the airways appears to be favorable to respiratory health.² 

What does the study tell us? Having siblings in early childhood impacts microbiota development and health. On the other hand, siblings make it easier for children to be contaminated by microbes that cause colds and other illnesses. However, the researchers believe that early exposure to relatively harmless microbes can reduce the risk of allergic diseases.³

What is menopause? When does it occur? What are the main symptoms? 

Prof. Ina Schuppe Koistinen: Menopause is the time in a women’s life that marks the end of the reproductive period while for most many years of life remain. Menopause is defined retrospectively after a woman has ceased menstruation for 12 months.

The menopausal transition occurs over a time period of several years starting in the age between 40 to 50. During that time, also called perimenopause, the ovaries decrease their production of the female sex hormones estradiol and progesterone. After the final menstruation, ovarian follicles are depleted, and sex hormone levels stay low. However, it is crucial to remember that many women witness that life after 50 is their best time, with more freedom, no menses, no pre-menstrual symptoms (sidenote: Premenstrual symptoms This refers to the symptoms women can experience in the weeks before their period (breast pain, mood swings, irritability, depression, fatigue…) Gudipally PR, Sharma GK. Premenstrual Syndrome. 2022 Jul 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan ) or pregnancies.

How does the vaginal microbiota evolve during menopause?

I. S.-K.: The vaginal microbiota in healthy women during the fertile years is dominated by Lactobacillus (sidenote: Lactobacilli Rod-shaped bacteria whose main characteristic is the production of lactic acid, from where they get the name “lactic acid bacteria”.  Lactobacilli are present in the oral, vaginal and gut microbiota of humans, but also in plants and animals. They are found in fermented foods, such as dairy products (e.g. certain cheeses and yoghurts), pickles, sauerkraut, etc. Lactobacilli are also found in probiotics, with certain species recognized for their beneficial properties.   W. H. Holzapfel et B. J. Wood, The Genera of Lactic Acid Bacteria, 2, Springer-Verlag, 1st ed. 1995 (2012), 411 p. « The genus Lactobacillus par W. P. Hammes, R. F. Vogel Tannock GW. A special fondness for lactobacilli. Appl Environ Microbiol. 2004 Jun;70(6):3189-94. Smith TJ, Rigassio-Radler D, Denmark R, et al. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr. 2013 Jun;109(11):1999-2007. ) species that protect the vagina from overgrowth of other organisms.

The composition of the vaginal microbiota is influenced by estrogen that promotes the proliferation of vaginal epithelial cells and increases glycogen storage, the main nutrient for lactobacillus growth. With decreasing levels of estrogen during the menopausal transition, the diversity of the vaginal microbiota increases while lactobacilli decrease^1,2.

Urinary tract infections are common among menopausal women. What’s the link with microbiota?

I. S.-K.: Women after menopause often suffer from urinary tract infections. Clinical data³ suggest an impact of estrogen on the pathogenesis of those infections. The low estrogen levels induce structural changes such as increased residual urine volume and changes in the vaginal microbiota as described above. Both are well documented risk factors for urinary tract infections. Local supplementation with estrogen can at least partly reverse these changes by the re-establishment of a lactobacilli-dominated vaginal microbiota and improved epithelial cell growth in the urogenital tract⁴.

Can menopause affect gut microbiota?

I. S.-K.: There are very few research studies in the scientific literature that have described the changes of the gut microbiota after menopause transition. So far, data⁵ from samples including less than 200 women have been analyzed to study the effect of menopause on the gut microbiota and few changes have been detected. More high-quality studies with samples from thousands of women are needed to describe and understand the effect.

Any advice to taking care of its microbiota (vaginal, gut) during this period?

I. S.-K.: My advice is to take good care of your general health by lifestyle choices that promote a healthy microbiota. Taking good care of the gut microbiota will help you to keep a healthy vagina. Eat a varied diet rich in fiber and fermented foods, stay physically active and spend time in nature. Do not smoke and keep your alcohol consumption low, avoid the use of antibiotics if possible.

Regarding the vaginal microbiota, avoid washing your vulva with soap and antiseptics, never rinse your vagina with perfumes or detergents as it cleans itself by its continuous discharge. Wash with lukewarm water or with perfume- and soap-free cleaning products. Use a neutral vegetable oil to keep the sensitive mucosal membranes of your vulva lubricated. Practice safe sex and if you experience dryness in your vagina use lubricants when having sex and consider a local treatment with an estrogen-containing cream.

Hormone therapy is used to treat menopause-related conditions and symptoms. Could prebiotics and probiotics complete this treatment?

I. S.-K.: It has been shown that women that passed menopause who underwent hormone replacement therapy had a similar lactobacillus-dominant composition of the vaginal microbiota to premenopausal women. With other words, hormone replacement therapy has a positive effect on the vaginal microbiota per se.

Prebiotics and probiotics could potentially contribute to a restoration of the vaginal microbiota to the state prior to menopause. This would require probiotics containing the right strains of Lactobacillus crispatus that are associated to good vaginal health.

Discover Prof. Ina Schuppe Koistinen's interview:

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Synopsis of the course

In recent years, the interest in researching the complex interaction between the human gut microbiota and our health has not stopped. Moreover, healthcare professionals have begun wondering if the initial establishment of the gut microbiota plays any role in our adult life. How is the microbiota formed and developed in infancy? How important is it later in life? In this course, you will learn about which factors influence our microbiota even before we are born, and what the consequences of an immature microbiota are later in adult life. Moreover, do not miss out on the practical recommendations on how to enhance a healthy, mature microbiota in children!Unrestricted grant by Biocodex Microbiota Institute

Who is Ericka Montijo?

• Ericka Montijo, MD, is a gastroenterologist working at the National Pediatric Institute in Mexico DF.
• She holds an MSc in pediatric nutrition and is specialized in pediatric endoscopies.
• Conflicts of Interest Statement: Ericka Montijo declares receiving consultation fees from Biocodex México/Reckit Mead Johnson and having participated as a speaker in a company-sponsored bureau organized by Biocodex México and Reckit Mead Johnson. 

What is Xpeer?

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

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

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

Information on accreditation

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

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

Initiated by MetaGenoPolis-INRAE and supported by INRAE with public institutions (APHP, Inserm…) and private partners, Le French Gut is the French part of an international project called the "Million Microbiomes from Humans Project" (MMHP). The objective is to build the world's largest database on microbiota with 1 million microbial samples from the intestine, mouth, skin, reproductive tract and other organs. Le French Gut will be contributed with its national collect.

Biocodex Microbiota Institute’s involvement

The Biocodex Microbiota Institute plays an active role in this initiative, producing and sharing exclusive news and informations on the Institute’s website and social networks (Facebook, Twitter, LinkedIn…) in order to favor the recruitment of volunteers.

With your help, we can make great strides in microbiota research to improve the quality of life of as many people as possible reaching our ambition to become the leader in microbiota care. By participating, you will help the research to explore innovative and personalized therapies for chronic diseases (diabetes, obesity, cancer...), neurodevelopmental disorders (autism...) and neurological diseases (Parkinson, Alzheimer...). We need your donation! If you are an adult, living in metropolitan France, follow the guide

Statins reduce the risk of atherosclerotic cardiovascular disease by inhibiting the activity of the 3-hydroxy-3-methylglutarate-coenzyme-A (HMG-CoA) reductase enzyme involved in the hepatic synthesis of low-density lipoprotein (LDL). Unfortunately, their effectiveness on LDL levels varies considerably among patients and adverse effects can occur, particularly insulin resistance, which increases the risk of type 2 diabetes mellitus. For physicians, determining the “maximum tolerated dose” for each patient based on the guidelines¹ is often down to trial and error. However, this approach wastes time and can undermine patient compliance.

A blood marker to measure response to statins

Recent studies have already shown links between the gut microbiota and atherosclerotic cardiovascular risk, but also between the microbiota and statin use. Now US researchers² have studied the gut flora’s role in responses to statins. By metabolizing statins, bacteria in the gut microbiota may modulate their bioavailability and potency to the host, or even contribute to their adverse effects. In a US cohort of 1,848 adults, 244 of whom were statin users, the researchers first validated a marker of statin response, plasma levels of the HMG-CoA reductase substrate, or HMG. HMG levels were found to be significantly higher in statin users than in non-users, and were negatively correlated with blood LDL levels in statin users only. The level of HMG reflected both the intensity of statin therapy and the presence of genetic variants in patients affecting their response to therapy.

Microbiota profile influences treatment efficacy and metabolic risk

The researchers then studied the association between statin efficacy as measured by HMG levels, the effect of statins on glucose control as measured by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score, and the composition of the gut microbiota, analyzed via 16S rRNA sequencing. They found that a more Bacteroides-enriched and diversity-depleted gut microbiome was associated with more intense statin responses, both in terms of efficacy and adverse effects on glucose control. However, a flora richer in Ruminococcaceae seemed to protect against the metabolic risk. These results were confirmed in a European cohort of 991 subjects whose gut microbiota was sequenced using a different method.

Towards precision statin therapies? 

This work not only explains variability in statin response, but also holds out the prospect of clinical tools to manage this variability. Indeed, plasma levels of HMG may supplement LDL levels as a source of information on treatment efficacy. Identifying the gut microbiota profile of patients may also allow us to predict responses to statins, to improve such responses using probiotics where necessary, and lastly, to propose to patients a more personalized treatment strategy for cardiovascular diseases.

It has the color and texture of milk – but it’s not milk. Horchata de chufa is a beverage made from tiger nuts (chufa, in Spanish) originally from Valencia, Spain. Not only refreshing, this drink also promotes the proliferation of gut bacteria beneficial to health.

So concluded researchers from the Spanish National Research Council (CSIC) after asking 31 healthy adults to drink a glass of horchata (300 ml) with their breakfast every morning for three days. The researchers collected stool samples from the volunteers before and after the experiment. Their aim was to analyze the effects of horchata on the bacteria of the gut microbiota.

Effects similar to those of a high-fiber diet

The results showed that the gut microbiota of all volunteers was positively modified by horchata². 

In general, the new bacterial profiles were similar to those of people following the Mediterranean diet (sidenote: Mediterranean diet Rich in fruit, vegetables, cereals, oilseeds (nuts) and fish, and low in red meat, saturated fats and dairy products. Lăcătușu CM, Grigorescu ED, Floria M, et al. The Mediterranean Diet: From an Environment-Driven Food Culture to an Emerging Medical Prescription. Int J Environ Res Public Health. 2019 Mar 15;16(6):942. ) or a diet rich in plants. In the volunteers’ gut microbiota, the researchers noted an abundance of bacteria that produce butyrate, a short-chain fatty acid (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. ) (SCFA) known for its numerous health benefits.

The changes observed also appear to have been dependent on the initial bacterial profile. Effectively, two main groups of microbiota could be distinguished after consumption of horchata, one enriched in Akkermansia, Christenellaceae, and Clostridiales, and the other with a remarkable presence of Faecalibacterium, Bifidobacterium, and Lachnospira. Some of these bacteria were already known for their beneficial effects on health, such as:

• better weight control,
• a reduced risk of diabetes mellitus,
• and improved immune responses,
• among others...

High in resistant starch and polyphenols: viva la chufa!

What explains these changes?

Tiger nuts (Cyperus esculentus), from which horchata is made, have a relatively high content of resistant starch. According to the researchers, this compound may “feed’ certain beneficial bacteria, such as Akkermansia, Lactobacillus, and Bifidobacterium, thus promoting their development.

Tiger nuts also contain numerous polyphenols which, thanks to their antimicrobial action, help slow down the proliferation of other bacterial species.

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The French Gut is part of a vast international project, the "Million Microbiome of Humans Project" (MMHP), which brings together several research institutes around the world. The MMHP's ambition is to create the world's largest database on human microbiota, by collecting one million microbial samples from the intestines, mouth, skin and reproductive tract of volunteer subjects. The French Gut, led by INRAE in partnership with public and private players involved in the microbiota field, will make a significant contribution to the development of this international database by collecting 100,000 French intestinal metagenomes.

The French Gut can count on the strong support of the Biocodex Microbiota Institute. The objectives of this project are to recruit 100,000 participants, and to raise awareness among the general public, including healthcare professionals, of the fascinating powers of the intestinal microbiota, particularly its role in the onset of a number of pathologies.

A shared objective: to highlight the importance of the effects of the intestinal microbiota on our health

The Biocodex Microbiota Institute shares the same ambition as Le French Gut: to raise awareness among the general public and train healthcare professionals in the major importance of the microbiota, particularly the impact of dysbiosis on our health. Since 2017, the Biocodex Microbiota Institute:

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Bile acids are currently a hot topic in research: in addition to helping the absorption of nutrients, they may play an important role in interactions between gut microbiota and host. Following their synthesis in the liver, bile acids are released into the gut and transformed by bacteria whose activity influences the composition of the gut microbiota. Reabsorbed by the colon, these “secondary” bile acids may then act as signaling molecules in various metabolic and immune processes.²

Sequencing, metabolomics, and statistics

Chinese researchers have put forward the idea that the gut microbiota and bile acids are involved in the still poorly understood relationship between chronic insomnia and cardiometabolic disease. Several recent discoveries have led them down this path. For example, the gut microbiota has its own circadian rhythms, different from that of the host and sensitive to insomnia. In mice, repeated sleep interruptions modify gut microbiota composition and the metabolism of bile acids. Lastly, gut microbiota dysbiosis and the dysregulation of bile acid metabolism both impair metabolic health.

To test their hypothesis, the researchers used two cohorts, a “discovery cohort” (sidenote: Discovery cohort The “discovery cohort” included 1,809 subjects from the prospective Guangzhou Nutrition and Health Study (GNHS) ) and a “validation cohort” (sidenote: Validation cohort The “validation cohort” included 6,122 participants from the cross-sectional Guangdong Gut Microbiome Project (GGMP), whose gut microbiota was sequenced by the researchers. ) . They collected detailed information on the subjects’ sleep and cardiometabolic parameters over a six-year period prior to the collection of the stool samples. Lastly, they analyzed the fecal bile acid metabolome of 954 subjects from the Guangzhou Nutrition and Health Study (GNHS) cohort.

Two bacterial genera and specific bile acids stand out

The researchers showed that chronic insomnia and cardiometabolic disorders were correlated with lower levels of two bacteria from the Ruminococcaceae family in both cohorts studied. By further analyzing the GNHS cohort, they also found that:

• Certain bile acids, such as isolithocholic acid (IsoLCA), murocholic acid (MCA), and norcholic acid (NorCA) mediated these associations. 
• Tea consumption (green, black, oolong, etc.) was associated with higher levels of Ruminococcaceae and lower levels of NorCA, as well as a decreased risk of insomnia.

Tea time to reduce the cardiometabolic risk of chronic insomnia?

The researchers believe that the gut microbiota-bile acid axis may be a potential intervention target for reducing the impact of chronic insomnia on cardiometabolic health. However, they remain cautious regarding tea: more research is needed to confirm that tea consumption has a beneficial effect on the bacteria in the microbiota linked to cardiometabolic health.

Contrary to popular belief, drinking water isn’t sterile: it contains 10-100 million microorganisms (sidenote: Microorganisms Living organisms that are too small to be seen with the naked eye. They include bacteria, viruses, fungi, archaea and protozoa, and are commonly referred to as “microbes”. What is microbiology? Microbiology Society. ) per liter! But not to worry, as previously shown by an Anglo-American study, these bacteria seem to feed our gut microbiota. Now Italian scientists have taken water samples from public fountains and domestic taps in the city of Parma with the aim of exploring microbial biodiversity in their city’s water and its effects on the gut microbiota of residents.

Water, a vehicle for significant bacterial diversity

Examining the samples, the researchers found that five bacterial species had a greater relative abundance, although with significant variability from one sample to another. For example, in one fountain, Acidovorax delafieldii represented more than half of the bacteria present, while in another the dominant bacterium was Sphingomonas ursincola, which made up a quarter of the bacteria found. Moreover, this variability was just as great in tap water. The five dominant species were no surprise, since they are known to be frequently found in drinking water. More surprising was the fact that a large proportion of the bacteria present in drinking water, whether from fountains or the tap, were unknown, a sort of microbial “dark matter” that scientists must now explore.

From a glass of water to the gut microbiota

Given that we drink about two liters of water per day, do these bacteria have an impact on our gut microbiota? Yes, say the researchers, who detected the bacteria in the stool of regular tap water drinkers, with presence profiles that reflect the composition of the water consumed. In other words, day in, day out, tap water helps shape our gut microbiota. The researchers even showed that some bacteria appear to settle permanently (and remain even when we drink bottled water), while the presence of others seems closely linked to regular consumption (they disappear when we drink bottled water for several days).

These preliminary findings are somewhat incomplete but they open two fields of research still only superficially explored. Firstly, what bacteria are present in drinking water? Secondly, what influence does the water we drink have on our gut microbiota and our health? Water still has secrets hiding below the surface...