A gene catalog for the vaginal microbiota

A catalog of all vaginal bacterial species and their gene function is now available. This public resource will facilitate the work of researchers and provide a better understanding of the role played by vaginal microorganisms in women’s health.

The vaginal microbiota Could blood be used as an indicator of gut microbiota diversity? Role of the microbiota in gut-brain communication Role of antibiotics and microbiota in parkinson's disease
Actu PRO : Un catalogue des gènes du microbiote vaginal

By 2003, the complete human genome had been decoded. In 2008, genome decoding was launched for human microbial populations (MetaHIT and (sidenote: Human Microbiome Project ) projects), followed by an analysis of their health roles ( (sidenote: International Human Microbiome Consortium ) ). While these databases are essential for understanding the structure and function of microbial communities and their role in diseases, they mainly focus on the gut microbiota. This situation changed in early 2020 with the publication of (sidenote: Vaginal integrated non-redundant gene catalog ) , a gene catalog for the vaginal microbiota.

VIRGO: the most complete vaginal gene catalog

VIRGO was built using metagenomic data (n = 264) and data from complete genomes (n = 308) gathered through urogenital samples and isolates. For the moment, the database mainly relates to bacteria, containing only a few viral and fungal gene sequences. It catalogs almost a million (sidenote: That do not create duplicate code for the same protein )  bacterial genes, classifying them both by taxonomic rank and function. VIRGO covers more than 95% of human vaginal microbiota and can be used for (sidenote: North America, Africa and Asia ) , making it possible to characterize genes and analyze their abundance and expression in the vaginal microenvironment. It has already shown that there is much more intra-species diversity within the vagina than previously thought, to the point of calling into question the idea that a major strain of Lactobacillus is dominant.

VOG: protein families grouped by function

The genes identified in VIRGO were then translated and grouped by protein family and function in a second catalog, VOG (Vaginal Orthologous Groups). The team used this catalog to search for new protein variants. The result was the identification of a previously unknown alanine-to-valine substitution in the protein sequence of a toxin excreted by Gardnerella vaginalis. The catalog will therefore make it possible to identify different variants of the same protein, suggest a biological significance for these variants and put forward new hypotheses.

A fast and accurate tool

VIRGO is a fast, accurate and multi-faceted tool for characterizing vaginal microbiota: it provides a global view of vaginal bacteria groups and has a gene-centric design that allows characterization by function and taxonomy; it also has high scalability, high sensitivity–making it possible to characterize low-abundant bacteria–, and is a simple tool for assessing genetic richness and intra-species diversity. It will be particularly valuable for users with limited computer skills, a large volume of data to sequence, and/or a limited computer infrastructure.

 

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Urinary microbiota in continent women: the effect of age

The composition of the urinary microbiota in continent adult women varies according to age, possibly due to the influence of hormones. Although certain urotypes seem to be emerging, the potential consequences are not yet understood.

The urinary microbiota Role of the microbiota in gut-brain communication The Janus face of Antibiotics: Life Savers and Microbiota Disruptors
Photo : Urinary microbiota in continent women: the effect of age

The bladder is not a sterile environment and the recent discovery of the urinary microbiota has opened up a whole new field of research. In this light, a cross-sectional study was carried out on 224 continent adult female patients at a large medical center in the United States, who were aged 48 years on average and were mostly Caucasian (66%) and overweight (average (sidenote: Body Mass Index.  Ratio of weight in kg to square of height in sq.m ) of 29.96 kg/m2). The subjects underwent a physical examination for a potential prolapse and were asked to fill in a questionnaire (overactive bladder, quality of life, weight, age, etc.). A urine sample taken by catheter was used to characterize their urinary microbiota.

Two methods of choice

Three methods of analysis were compared: the standard method, the expanded quantitative urine culture, or EQUC protocol (larger volume of urine, incubation under various conditions, extended incubation period) and RNA sequencing. With the standard method, bacteria were detected in 13 samples (6%), with the EQUC protocol in 115 (51%), and with RNA sequencing in 141 (63%), of which 89 were shared with the EQUC method. Therefore, the EQUC protocol and/or RNA sequencing appear to be the methods of choice, whereas the standard method is not recommended due to the high percentage of false negatives it produces.

Different urotypes

The results show that the microbiota in the bladder is variable, permitting the definition of urotypes based on the predominance (> 50%) of a taxon. The most common urotype was that dominated by Lactobacillus (19%), with no differences due to age, menopausal status, parity, sexual relations or even ethnicity (although the vaginal microbiota of black women is known to be more frequently dominated by lactobacilli). This was followed by the Streptococcus, mixed (no single taxon dominating), Gardnerella and Escherichia urotypes. The Gardnerella urotype was more common in younger women (average age of 36) and Escherichia in older women (average age of 60). The mixed urotype was frequently found in African American women (46%).

Causes and consequences?

Hormones may explain these differences in urotype, especially since they are known to have a beneficial effect on the growth of Lactobacillus in the vagina and lower urinary tract. However, the biological consequences remain a mystery. The different urotypes may provide protection from or result in a predisposition to various urinary disorders, including incontinence, overactivity or infections. In any case, the experts insist that medical treatment should preserve or restore the native urinary microbiota, particularly lactobacilli, as the disruption of this microbial community may increase susceptibility to infection.

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News Urology

Kidney transplant: is pre-operative dysbiosis a risk factor for diabetes?

Patients affected by kidney failure who develop diabetes following a transplant may have been suffering from a pre-operative gut dysbiosis, the precise details of which have not yet been determined.

The gut microbiota Kidney failure: impact of the gut microbiota Severity-specific signature of gut microbiota in chronic kidney disease Spinal cord injuries and colorectal disorders: impact of the gut microbiota
Actu PRO : Greffe rénale : la dysbiose préopératoire, facteur de diabète ?

Patients affected by kidney failure often suffer from severe metabolic disorders. Diabetes is the leading cause of end-stage kidney disease and subsequent renal transplants (RT), while 20% of patients who were normoglycemic prior to RT develop New-Onset Diabetes After Transplant (NODAT) within one year of their operation. The immunosuppressive treatment received by patients following RT is largely held responsible, since it is known to induce insulin resistance, but this does not explain why some patients are more resistant to the development of NODAT than others.

The gut microbiota suspected

A French team compared the fecal microbiota of 50 subjects with kidney failure before and (3 to 9 months) after RT. 16 of the subjects had type 2 diabetes (T2D) prior to transplantation, 15 developed NODAT and the remaining 19 (control subjects) were not diabetic before or after RT. The researchers focused on (sidenote: Firmicutes/Bacteroidetes ratio, Bacteroides-Prevotella group, Lactobacilli, Bifidobacteria, Akkermansia muciniphila, Faecalibacterium prausnitzii, Escherichia coli, Clostridium coccoides and Clostridium leptum. ) already linked to diabetes or metabolic disorders in mice and/or patients who have not received a kidney transplant.

Pre- and post-transplant differences

Prior to RT, Lactobacillus sp. was less frequently detected in control subjects (60%) than in NODAT patients (87.5%) or patients with T2D pre-transplant (100%). Following RT, its relative abundance increased by a factor of 20 and 25 in the NODAT and T2D groups, respectively. On the other hand, Akkermansia muciniphila decreased by a factor of 2,500 in the NODAT group and 50,000 in the T2D group. However, these alterations were not observed post-transplantation in the control subjects. Lastly, prior to RT, the relative abundance of Faecalibacterium prausnitzii was 30 times lower in T2D patients than in the control subjects.

A pre-transplant dysbiosis responsible for NODAT?

The authors’ conclusions? A dysbiosis prior to RT (characterized among other things by the presence of lactobacilli) may predispose patients to the development of NODAT, in the context of the consumption of immunosuppressive drugs favoring its onset. Larger-scale prospective studies not limited to the nine bacterial markers considered here will make it possible to describe in greater detail the role of the intestinal microbiota in the development of NODAT.

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Quarantined? Eat apples to help your gut

Did you know that you consume up to 100 million bacteria when biting into an apple? During quarantine and throughout the year, these microorganisms supplement your gut microbiota and help you maintain good health.

The gut microbiota Diet
Actu GP : Mangez des pommes, c’est bon pour votre microbiote intestinal !

An apple a day keeps the doctor away.” The explanation behind this old saying can be found in the abundance of vitamins, minerals and other antioxidants in this fruit, but not solely: apples are also an important source of microorganisms (bacteria, viruses, fungi) with many health benefits, which colonize and temporarily enrich our gut microbiota. Few studies have discussed these “good” microbes since most of them focus on microorganisms responsible for foodborne illness. This oversight has been corrected thanks to an Australian team, whose findings are published in the Frontiers in Microbiology journal.

Organic food provides greater diversity

Researchers analyzed all microorganisms hidden in flesh, skin, stem and seeds of apples, as well as the impact of the cultivation method used. Their first observation was that most bacteria are concentrated in the stem, seeds and calyx, which we usually do not eat. But flesh and skin also contain higher concentrations of bacteria. Another finding from the study was that the microbiota of organic apples while not more abundant was much more diversified and more homogeneous than that of conventional apples. This could limit the presence of harmful microorganisms that may cause foodborne illness. And good news: diversity was highest in the organic fruit’s flesh.

Bacteria that are good for our health

The study out of Australia also showed that organic apples mainly contain lactobacilli, with well-known beneficial properties, as well as another bacterial type responsible for the taste of strawberries. As to the microbiota of ordinary apples, it is strongly dominated by Enterobacteriaceae, a family of bacteria including some species (such as Escherichia coli) that are responsible for foodborne illness. The authors believe that these differences in microbial composition are due primarily to agricultural practices and storage conditions. And they hope to see, one day, this nutritional profile indicated on marketing labels, together with the content of macronutrients, vitamins and minerals.

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Wassermann B, Müller H, Berg G. An Apple a day: which bacteria do we eat with organic and conventional apples? Front. Cell. Infect. Microbiol. 10:1629. doi.org/10.3389/fmicb.2019.01629

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Semen, a reflection of a man’s intimate microbiota

A new method of semen analysis has the potential to replace traditional techniques. Used to detect microorganisms that colonize or infect the male genital tract, the traditional methods are considered too expensive for some laboratories or of limited use.

The vaginal microbiota Diet
Actu GP : Le sperme, reflet du microbiote intime de l’homme

Although it is by far the most well-known microbiota, as it is the most important and most studied, the gut microbiota is not the only microbial community in our body. Bacteria, viruses and yeasts colonize all our bodily fluids, even the most intimate. A team of American researchers has set out to identify and analyze the microorganisms present in semen using a technique normally used to assess whether genes are functional. Their aim was to determine whether this approach is suitable for evaluating the diversity of the microbiota in semen.

Less rich but more diverse than vaginal microbiota

The microorganisms residing in the male genital tract come mainly from direct contact with women during sexual intercourse. Escherichia coli, which is linked to genital and urethral infections, is the most frequently observed bacterium. The male genital microbiota shares 85% of its bacterial species with the vaginal microbiota but is less abundant and more diverse.

An infected sample

The researchers analyzed the semen of 85 men who were in a heterosexual relationship. The technique used by the researchers made it possible to identify the main bacteria colonizing the male genital tract. Only one sample had a very different microbial mix, showing a particularly high content in Streptococcus agalactiae. This bacterial species is responsible for sexual infections in both men and women and may lead to miscarriage or stillbirth in the latter. Its abundance is difficult to explain, with the most likely cause being infection via the subject’s partner.

An effective diagnostic technique

The authors conclude that this new method appears just as effective in diagnosing bacterial colonization or infection of semen as the method traditionally used to analyze human microbiota.

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Swanson GM, Moskovtsev S, Librach C, et al. What human sperm RNA-Seq tells us about the microbiome. J Assist Reprod Genet. 2020 Feb;37(2):359-368.

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Effects of intermittent fasting on the gut microbiota

Whether for religious reasons or as part of the fasting trend, intermittent fasting is likely to have an impact on our gut microbiota. Although demonstrated in mice, no study had, until now, been carried out among humans and even less so during Ramadan.

The gut microbiota Diet

Fasting and its effects on the makeup of the intestinal microbiota have been the subject of very few studies because they are difficult to model. However, since diet is one of the main environmental factors that can shape our gut microbiota, it is not hard to imagine that prolonged food deprivation may change the composition of this microbial community. Accordingly, a team of Turkish researchers carried out a small study with nine Muslim subjects (seven women and two men) who fasted during Ramadan. A pillar of Islam, this age-old practice involves abstaining from food and drink from sunrise to sunset for a period of 29 days. In the study, conducted between 18 June and 16 July 2015, daily fasts lasted 17 hours.

A healthier gut microbiota

At the end of Ramadan, stool samples obtained from the participants showed a higher abundance of the good bacteria Bacteroides fragilis and Akkermansia muciniphila. The latter group makes up 3%-5% of the microbial community in healthy individuals but this proportion is lower for the obese. Conversely, the abundance of other bacteria decreased, although not significantly. Fast also resulted in a reduction in total cholesterol and fasting blood sugar levels, confirming the results of another study. However, the authors did not observe the significant decrease in participants’ (sidenote: Body Mass Index.  Ratio of weight in kg to square of height in sq.m ) * seen in other studies, presumably because of the small number of subjects involved.

Resistance to change

The authors suggest that the improved makeup of the gut microbiota after fasting is due to the resistance of beneficial bacteria species, such as Bacteroides and Akkermansia, to dietary changes. These results are preliminary and require confirmation in larger studies, but they provide a better understanding of the relationship between fasting and the intestinal microbiota.

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Özkul C, Yalınay M, Karakan T. Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group: A preliminary study on intermittent fasting. Turk J Gastroenterol 2019; 30(12): 1030-5.

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What to drink during the lockdown? Orange juice is good for your microbiota!

Caring for your gut microbiota (or gut flora) starts at breakfast. Daily consumption of orange juice could improve the composition and functioning of the gut microbiota. More generally, it could have positive effects on health, according to a Brazilian study published in the Journal of Medicinal Food.

The gut microbiota Diet Prebiotics: what you need to know
Actu GP : Le jus d’orange, c’est bon pour votre microbiote !

A look at oranges under a magnifying glass

Oranges and citruses are not only known for their high content of ascorbic acid (vitamin C) and carotenoids, but they also are a major source of flavonoids–which have antioxidant, anti-inflammatory, antitumoral and lipid-lowering properties. These fruits are believed to preserve our health and protect us from chronic diseases.

30 cl of orange juice per day

In a small clinical trial, researchers from São Paulo measured the effects of the daily consumption of pasteurized orange juice on the composition of the gut microbiota and the metabolism of 10 healthy young women. During the first month, participants were instructed to drink and eat according to their dietary habits, but avoiding sources of flavonoids, prebiotics and probiotics, as well as alcoholic beverages. The objective was to start the experimental period with low contents of tested substances in order to measure the effect of citruses. During the next two months, they had to drink 30cl of industrial orange juice every day; and the last month they resumed their dietary habits but excluding orange juice. Blood and stool samples were taken, and several biological parameters were measured at the end of each period.

Microbiota enriched with “good” bacteria

Daily consumption of orange juice led to a significant drop in glucose, insulin, triglycerides, total cholesterol, LDL-cholesterol (“bad” cholesterol) levels, as well as in insulin resistance. Gut microbiota had a higher abundance of some microorganisms, especially species able to grow in the absence of oxygen (“anaerobic” microorganisms), as well as lactobacilli and bifidobacteria which have health benefits. While ammonium production, rather harmful to the intestines, temporarily dropped, the production of molecules that are indicative of a healthy microbiota increased. The authors concluded that orange juice could thus act as a prebiotic, by promoting the growth or activity of gut bacteria that are beneficial to our health, and they urge us to drink it daily.

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Sivieri K et al. Effect of Daily Consumption of Orange Juice on the Levels of Blood Glucose, Lipids, and Gut Microbiota Metabolites: Controlled Clinical Trials. J Med Food 00 (0) 2019, 1–9

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Microbiota, breastfeeding and early puberty

Maternal high-fat diet during lactation disrupts the intestinal microbiota of young mice, increases the likelihood of early puberty in young females and generates insulin insensitivity. The sharing of microbiota, through cohabitation with the offspring of mothers fed on a regular diet, reverses this trend.

The gut microbiota Peripartum prophylactic antibiotic therapy decreases bifidobacterium levels in breast milk Can fecal transplantation restore the microbiota of Caesarean-born infants? Gut microbiota not yet considered “adult” at 5 years old?
Photo : Microbiota, breastfeeding and early puberty

Each year, early puberty affects 20 out of every 10,000 girls worldwide, with childhood obesity increasing the risk of occurrence. Since 2010, greater attention has been paid to the effects of the intestinal microbiota on energy homeostasis and obesity. Although many factors may influence the gut microbiota (use of antibiotics, etc.), breastfeeding seems to play a primary role in its development. Researchers have therefore manipulated the diet of lactating female mice in order to assess the influence of diet on the risk of obesity and early puberty among their offspring. For three weeks from the birth of their pups, female mice were fed either a normal calorie diet (NCD) containing 12% fat or a high-fat diet (HFD) containing 60% fat. 21 days after birth, all the young mice were weaned, fed a normal calorie diet and randomly placed in cages alongside four young mice from NCD mothers, four young mice from HFD mothers or two young mice from NCD mothers and two young mice from HFD mothers. The goal was to measure the impact of this cohabitation and assess whether it reversed any effects of a maternal high-fat diet upon offspring.

Impact of maternal diet during breastfeeding

A high-fat diet for mothers during lactation influenced the development of their offspring’s microbiota. For example, there was an increase in the proportion of Streptococcaceae and Peptostreptococcaceae in the intestinal microbiota of the young mice. In addition, the offspring of HFD mothers had microbiota with significantly less richness. A maternal high-fat diet also resulted in childhood obesity, early puberty, irregular menstrual cycles and signs of impaired glucose metabolism in female offspring. However, early puberty was not observed in young males.

Effects of sharing microbiota

Since mice are coprophagous animals, they share their microbiota via the fecal-oral route. Following cohabitation with the offspring of NCD mothers, the offspring of HFD mothers saw the abundance of their microbiota increase, reversing the effects of the maternal high-fat diet. This also protected females against early puberty and insensitivity to insulin. However, no protective effect was observed on the weight or body fat of HFD offspring.

A new therapeutic approach for metabolic disorders?

According to the authors, breastfeeding plays a critical role in the development of a normal metabolic and reproductive function among offspring. Insulin resistance associated with a microbiota dysbiosis increases the likelihood of early puberty where this results from a high-fat maternal diet during breastfeeding. Consequently, microbiota may represent a new therapeutic target in the treatment of metabolic and reproductive disorders.

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Is the gut microbiota the key to high-quality sleep?

Have you ever wondered why you get so sleepy in a very stressful situation? We found the culprit: the gut-brain axis! taking care of your gut microbiota (or gut flora) would affect mental and physical health. It’s time to reset your sleep cycle!

The gut microbiota Diet
Actu GP : Le microbiote intestinal, la clé d’un sommeil de qualité ?

Several studies have shown that sleep is highly dependent on the quality of the gut microbiota, with which it is constantly interacting. While a depletion in bacterial flora leads to a decrease in sleep duration, chronic sleep disorders or alterations of the sleep-wake rhythm lead in turn to an imbalance of the microbiota (called “dysbiosis”).

Butyrate: a sleep-promoting agent?

Butyrate is a substance produced by the fermentation of dietary fiber under the influence of the gut microbiota. According to a new study published in the Scientific Reports journal, it seems to play a major role in sleep onset and sleep quality...Researchers from the University of Washington aimed at identifying molecules used as sleep-inducing signals. They focused primarily on butyrate, a short-chain fatty acid mainly found in dairy products and fiber from many plants (asparagus, oat flakes, artichokes, raw garlic, leeks, onions). When produced by the intestines under the action of specific bacteria, butyrate enters into the portal vein, a large blood vessel that transports it to the liver, where it is stored. According to the researchers’ hypothesis, it acts on the portal vein’s sensory mechanisms in order to promote sleep.

Increase in deep sleep

Butyrate was thus tested in rodents according to three modes of administration. Subcutaneous injection, which is supposed to act on the entire organism, had no effect. On the contrary, oral administration increased the duration of (sidenote: Deep sleep Sleep phase ensuring optimal recovery of the body. ) by around 50%, decreased body temperature, and reduced episodes of (sidenote: paradoxical sleep Also known as REM sleep (Rapid Eye Movement); it is the last phase of a complete sleep cycle and it is when we dream. ) . Direct injection into the portal vein had similar, but enhanced, effects, confirming the involvement of the liver in the process.

Eat better to sleep better!

Butyrate seems to trigger sleep by binding to receptors located on the wall of the liver and/or portal vein. Taking care of your gut microbiota by consuming foods that contain butyrate (dairy products, butter and cheese for example) or promote the production of butyrate could thus improve sleep disorders. It is probably a healthier and more natural solution than sleeping pills!

Recommended by our community

"#LoveYourMicrobiome To Have A Happy and Healthy Sleeping 😴" Dr. Kayasseh Microbiome Center (From My health, my microbiota)

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Szentirmai E, Millican NS, Massie AR, et al. Butyrate, a metabolite of intestinal bacteria, enhances sleep. Scientific Reports. 2019 ; 9:7035

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