The pulmonary microbiota

Why is the lung microbiota so important for health?

Researchers long held the view that the lungs of healthy individuals were sterile.1 That's not the case, though! It's just 10 years since medicine discovered the abundance of lung microbiota.2 Unlocking its secrets since then has proved a major challenge.

Pulmonary Tract Microbiota

What is the lung microbiota?

In contrast to its big brother, gut microbiota, it is only very recently that lung microbiota has been investigated. This delay can be partly explained by the difficulty of collecting samples and accessing the lungs themselves, both of which often require the use of an invasive method.3 In addition, the risk of bacterial infection of the upper airways is a real issue.4 Lung flora was first identified in 2010;5 there have since been very few studies devoted to elucidating the role of the communities of micro-organisms that live there.3  

Nonetheless, our understanding of the composition of the lung microbiota can be summed up in three points:

  • Low density of bacteria5
  • High level of biodiversity. In healthy individuals, bacteria from the Prevotella, Veillonella, Streptococcus, Neisseria, Fusobacterium and Haemophilus5 genera are predominant in the lungs. Maintaining the balance of this bacteria relies on the rhythm of inhalation and exhalation6
  • A tremendous abundance of “anaerobic” bacteria, which develop in the absence of oxygen. These are species of bacteria belonging to the Fusobacterium, Porphyromonas, Prevotella and Veillonella7 genera

Nor are bacteria the only (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. ) that develop in the lung microbiota of healthy individuals! Fungi (species belonging to the Eremothecium, Systenostrema and Malassezia genera and to the Davidiellaceae family) and viruses (member species of the Anelloviridae family, along with a large number of (sidenote: Bacteriophage Virus that specifically targets and infects bacteria Scitable by Nature education_2014. Bacteriophage definition ) ) are also found to live there.2 Recent discoveries have also identified the presence of (sidenote: Archaea Type of micro-organism (different from bacteria) found in all environments, including extreme environments Archaea. Microbiology Society )  in the lungs.8 Lastly, while these micro-organisms form an integral part of the lung microbiota, the data currently available are limited. 

Why does the lung microbiota play a major role in our health?

The lung microbiota plays a key role in maintaining the balance of lung function. It acts in four major ways:

  • As a barrier to pathogens and an aid to resistance against respiratory infections,9 in exactly the same way as the gut microbiota
  • It plays a defensive role by actively helping to stimulate (sidenote: Innate and adaptive immunity  The human body protects itself using two kinds of defense mechanisms: innate immunity and adaptive immunity. Innate immunity is the first line of defense against disease agents and is an immediate response, while adaptive immunity is delayed but provides lasting protection Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Principles of innate and adaptive immunity. ) in case of infections10,11
  • It is involved in the maturation of the pulmonary immune system, enabling, inter alia, tolerance to allergens12
  • It affects the morphology of the lungs and more specifically, the number of pulmonary alveoli, according to studies in mice13

Diseases linked to an imbalance in lung microbiota

When there is an imbalance in the composition of the lung microbiota, a (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) 14 emerges, which may be linked to various diseases. Scientific studies to date have not always been able to determine whether the dysbiosis causes or results from such diseases, though.

Let’s take a closer look at the disorders linked to pulmonary dysbiosis:

  • winter respiratory infections such as colds and flu (most often viral), where there is an imbalance in lung immunity, along with dysbiosis15 in the lungs and gut
  • asthma:16 a chronic disease of the respiratory system affecting more than 260 million people worldwide.17 This condition is associated with an imbalance in the lung microbiota,16 as well as in gut18 and nasal19 microbiota
  • cystic fibrosis, a rare genetic disease that mainly affects the airways and the digestive system20
  • chronic obstructive pulmonary disease (COPD), which is characterised by progressive narrowing and permanent obstruction of the airways and lungs, causing difficulty breathing16

The “gut-lung axis”

These conditions highlight the bidirectional communication between the gut and the lungs, known as the “gut-lung axis”.15 Gut microbiota plays a role in pulmonary immune response and lung diseases can also influence the composition of the intestinal microbiota.15 In fact, many respiratory diseases go hand in hand with gastrointestinal disorders21 and, conversely, intestinal dysbiosis is often linked to lung diseases.16 The involvement of this axis in pulmonary diseases is a highly promising area for research.22

Looking after your lung microbiota

You now know about the important role played by the lung microbiota and the gut-lung axis in your health. Researchers have grasped this fully and are currently investigating strategies to prevent or cure lung infections.23,24

When it comes to preventing winter respiratory infections, there have been some encouraging results when combining probiotics with prebiotics.25 In infants, certain probiotics may well prevent winter infections as early as the first few months of life.26 Lastly, some studies in students have demonstrated the value of using probiotic treatment to achieve a significant reduction in symptom duration.27,28
 

All the information in this article is derived from accepted scientific sources. It should be remembered that this information is not exhaustive. The list of studies from which this information has been extracted can be found here.     

Sources

Hufnagl K, Pali-Schöll I, Roth-Walter F, et al. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin Immunopathol. 2020;42(1):75-93.

Barcik W, Boutin RCT, Sokolowska M, et al. The Role of Lung and Gut Microbiota in the Pathology of Asthma. Immunity. 2020;52(2):241-255.

Huffnagle GB, Dickson RP, Lukacs NW. The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunol. 2017 Mar;10(2):299-306.

Dickson RP, Erb-Downward JR, Freeman CM, et al. Bacterial Topography of the Healthy Human Lower Respiratory Tract. mBio. 2017 Feb 14;8(1):e02287-16.

Hilty M, Burke C, Pedro H, et al. Disordered microbial communities in asthmatic airways. PLoS One. 2010 Jan 5;5(1):e8578.

Mathieu E, Escribano-Vazquez U, Descamps D, et al. Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma. Front Physiol. 2018 Aug 21;9:1168.v

Lamoureux C, Guilloux CA, Beauruelle C, et al. Anaerobes in cystic fibrosis patients' airways. Crit Rev Microbiol. 2019 Feb;45(1):103-117. 

Koskinen K, Pausan MR, Perras AK, et al. First Insights into the Diverse Human Archaeome: Specific Detection of Archaea in the Gastrointestinal Tract, Lung, and Nose and on Skin. mBio. 2017 Nov 14;8(6):e00824-17.

Brown RL, Sequeira RP, Clarke TB. The microbiota protects against respiratory infection via GM-CSF signaling. Nat Commun. 2017 Nov 15;8(1):1512.

10 Karmarkar D, Rock KL. Microbiota signalling through MyD88 is necessary for a systemic neutrophilic inflammatory response. Immunology. 2013 Dec;140(4):483-92.

11 Pichon M, Lina B, Josset L. Impact of the Respiratory Microbiome on Host Responses to Respiratory Viral Infection. Vaccines (Basel). 2017 Nov 3;5(4):40.

12 Gollwitzer ES, Saglani S, Trompette A, et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat Med. 2014 Jun;20(6):642-7.

13 Yun Y, Srinivas G, Kuenzel S, et al. Environmentally determined differences in the murine lung microbiota and their relation to alveolar architecture. PLoS One. 2014 Dec 3;9(12):e113466.

14 Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.

15 Dumas A, Bernard L, Poquet Y, et al. The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol. 2018 Dec;20(12):e12966.

16 Budden KF, Shukla SD, Rehman SF, et al. Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med. 2019 Oct;7(10):907-920.

17 World Health Organization. 2021. Asthma. World Health Organization, Geneva, Switzerland. https://www.who.int/news-room/fact-sheets/detail/asthm

18 Abrahamsson TR, Jakobsson HE, Andersson AF, et al. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014 Jun;44(6):842-50.

19 Kang HM, Kang JH. Effects of nasopharyngeal microbiota in respiratory infections and allergies. Clin Exp Pediatr. 2021 Apr 15.

20 Hardouin P, Chiron R, Marchandin H, et al. Metaproteomics to Decipher CF Host-Microbiota Interactions: Overview, Challenges and Future Perspectives. Genes (Basel). 2021 Jun 9;12(6):892.

21 Sencio V, Machado MG, Trottein F. The lung-gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes. Mucosal Immunol. 2021 Mar;14(2):296-304.

22 Budden KF, Gellatly SL, Wood DL, et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol. 2017 Jan;15(1):55-63.

23 Park MK, Ngo V, Kwon YM, et al. Lactobacillus plantarum DK119 as a probiotic confers protection against influenza virus by modulating innate immunity. PLoS One. 2013 Oct 4;8(10):e75368.

24 Belkacem N, Serafini N, Wheeler R, et al. Lactobacillus paracasei feeding improves immune control of influenza infection in mice. PLoS One. 2017 Sep 20;12(9):e0184976.

25 Pregliasco F, Anselmi G, Fonte L, et al. A new chance of preventing winter diseases by the administration of synbiotic formulations. J Clin Gastroenterol. 2008 Sep;42 Suppl 3 Pt 2:S224-33.

26 Rautava S, Salminen S, Isolauri E. Specific probiotics in reducing the risk of acute infections in infancy--a randomised, double-blind, placebo-controlled study. Br J Nutr. 2009 Jun;101(11):1722-6.

27 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.

28 Wang Y, Li X, Ge T, et al. Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016 Aug;95(31):e4509.

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The urinary microbiota

The urinary microbiota: what is it and why is it so important for our health?

The human urinary tract is inhabited by numerous microorganisms that can play a protective role in our health.1 Reduced diversity in the urinary flora may also be a risk factor for disease.2 In fact, urine was once thought to be sterile, but recent scientific research has shown the opposite to be the case.2 Continue reading to see how research on the urinary microbiota is evolving.

Urinary microbiota

What is exactly the human urinary microbiota?

You have probably heard less about the urinary microbiota than its more well-known neighbors, the gut microbiota and the vaginal microbiota. This is no surprise, since it is a less rich and diverse environment3 whose role requires further research.1

However, recent studies have shown that the urinary tract is home to a unique urinary microbiota.4,5 Urine analyses based on culture-dependent methods have traditionally identified (sidenote: Pathogens A pathogen is a microorganism that causes, or may cause, disease. Pirofski LA, Casadevall A. Q and A: What is a pathogen? A question that begs the point. BMC Biol. 2012 Jan 31;10:6. ) responsible for urinary tract infections (UTIs), such as Escherichia coli.

Advances in detection technologies have led to the discovery of additional bacteria in the urinary microbiota. The genus Lactobacillus is frequently identified, while Gardnerella, Streptococcus, and Corynebacterium also tend to be present, although to a lesser degree.3 In addition, communities of fungi have also been observed.6 

Moreover, although the number of studies in the area remains limited, the composition of the urinary microbiota of women appears to be different from that of men,7 which is not surprising given the anatomical and hormonal differences between the two sexes.

Why is the urinary microbiota a key player in our health?

(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. ) inhabiting the urinary microbiota can play a protective role in our health.1 However, under certain conditions, they can also influence urinary tract infections.2

Several mechanisms have been described: for example, the bacterial genera Lactobacillus and Streptococcus secrete lactic acid, which is believed to play a protective role against pathogens.8 Lactic acid lowers the pH of urine (≈ 4.5), creating a microenvironment that is hostile to most pathogenic bacteria.

Furthermore, (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. ) produces additional substances, antibacterial metabolites such as hydrogen peroxide, which also protect against pathogens.9 As with the gut microbiota, the urinary microbiota acts as a barrier against pathogens.1

What diseases are associated with an unbalanced urinary microbiota?

As with all microbiota (gut microbiota, lung microbiota, etc.), when the composition of the urinary microbiota is disrupted, an imbalance, or “ (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) ”,9 results. Studies comparing the urinary microbiota of healthy subjects to that of patients suffering from various urinary diseases have identified a link between these diseases and the composition of the urinary microbiota.

In fact, studies published to date have demonstrated a clear role for the urinary microbiota in urinary tract infections (UTIs).8,10 For example, decreased diversity in the urinary microbiota may be a risk factor for urinary tract infections.11

Furthermore, disorders such as urgency urinary incontinence,12 interstitial cystitis,13 and sexually transmitted infections14 have also been associated with an altered urinary microbiota.

How can we take care of our microbiota? We can have a direct influence on it.

  • Diet: it is common knowledge that dietary factors can influence the risk of urinary tract infections. Certain food and dietary products (such as cranberry juice or fermented dairy products containing probiotics) may help reduce the risk of recurrent infection by regulating the microbiota.8

  • Probiotics: oral and vaginal probiotic have been successful in decreasing recurrence rates for UTIs.15

  • Water: drinking plenty of water is important, but researchers have not yet confirmed that it can cure UTIs.1

All the information in this article comes from scientific approved sources. Keep in mind this is not exhaustive. Here are all the studies from which we took all of that information.

References

Whiteside SA, Razvi H, Dave S, et al. The microbiome of the urinary tract--a role beyond infection. Nat Rev Urol. 2015 Feb;12(2):81-90.

2 Morand A, Cornu F, Dufour JC, et al. Human Bacterial Repertoire of the Urinary Tract: a Potential Paradigm Shift. J Clin Microbiol. 2019 Feb 27;57(3). 

Brubaker L, Wolfe AJ. The female urinary microbiota, urinary health and common urinary disorders. Ann Transl Med. 2017 Jan;5(2):34.

4 Hilt EE, McKinley K, Pearce MM, et al. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014 Mar;52(3):871-6.

Pearce MM, Hilt EE, Rosenfeld AB, et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014 Jul 8;5(4):e01283-14.

6 Ackerman AL, Underhill DM. The mycobiome of the human urinary tract: potential roles for fungi in urology. Ann Transl Med. 2017 Jan;5(2):31. 

Lewis DA, Brown R, Williams J, et al. The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Front Cell Infect Microbiol. 2013 Aug 15;3:41.

8 Aragón IM, Herrera-Imbroda B, Queipo-Ortuño MI, et al. The Urinary Tract Microbiome in Health and Disease. Eur Urol Focus. 2018 Jan;4(1):128-138. 

9 Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232

10 Antunes-Lopes T, Vale L, Coelho AM, et al. The Role of Urinary Microbiota in Lower Urinary Tract Dysfunction: A Systematic Review. Eur Urol Focus. 2020 Mar 15;6(2):361-369. 

11 Horwitz D, McCue T, Mapes AC, et al. Decreased microbiota diversity associated with urinary tract infection in a trial of bacterial interference. J Infect. 2015 Sep;71(3):358-367.

12 Pearce MM, Hilt EE, Rosenfeld AB, et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014 Jul 8;5(4):e01283-14.

13 Siddiqui H, Lagesen K, Nederbragt AJ, et al. Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol. 2012 Sep 13;12:205.

14 Nelson DE, Van Der Pol B, Dong Q, et al. Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLoS One. 2010 Nov 24;5(11):e14116.

15 Stapleton AE, Au-Yeung M, Hooton TM, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011 May;52(10):1212-7.

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The gut microbiota

Gut microbiota: why is it that important for your health?
We have trillions1 of bacteria that populate our intestine with fascinating powers on the human body. Let’s understand how your intestinal microbiota works and why you should take care of it! 

The Gut microbiota

What is exactly the human gut microbiota?

You probably have already heard about the “gut flora”, well, scientifically, it is called “the intestinal microbiota” or to put it more simply “the gut microbiota”. What is the definition of gut microbiota ? It consists of trillions1 of (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. ) that populate your intestines like bacteria, viruses, fungi (including yeasts), and even parasites.

By the way, microbiota and microbiome are two words often used as one to the other but they have two different meanings while microbiota is used to talk about the microorganism and answer the question “who is there?” basically the “individuals”, the microbiome talks about their genome “what is inside of them”2 to answer the question “what are they doing” meaning their function.

Each one of us has a unique microbiota, like a fingerprint.1 When you’re born, fecal and vaginal microorganisms transmitted by your mother during vaginal delivery, or environmental microorganisms for cesarean delivery,3 induce the start of your gut microbiota colonization4. It takes around three years for the gut microbiota to build up, diversify and stabilize.5 During adulthood,6 the composition is relatively stable until old age when it undergoes profound changes again to become slightly impoverished.7

100 000 100,000 billion “good” bacteria live in our gut

2nd the gut microbiota is often considered as the second brain

Why is gut microbiota important for your health?

The gut microbiota can be considered a functional organ of the human body. Why should we take care of our microbiota ? It works closely with your intestines and have 4 important roles:

It promotes digestion

by helping with the absorption of nutrients (sugars, amino acids, vitamins…) by intestinal cells or with the fermentation of the small fraction of food. These fermentation processes produce gas and numerous metabolites, including short-chain fatty acids, a real “fuel” for the cells in your colon.8

It plays an important role in the maturation of the digestive tract

by having an active role in the production of gastrointestinal mucus, the irrigation of intestinal cells, and the enzymatic activity of the mucosa.9

It works as a barrier

against pathogens and toxins.10 Furthermore, some bacteria release antimicrobial molecules against the (sidenote: Pathogens A pathogen is a microorganism that causes, or may cause, disease. Pirofski LA, Casadevall A. Q and A: What is a pathogen? A question that begs the point. BMC Biol. 2012 Jan 31;10:6. ) bacteria while others stimulate the production of mucus to protect intestinal cells from attacks and avoid harmful effects on your body.11

It plays a defensive role

in developing the human immune system. Bacteria of the gut flora are involved in the maturation and activation of cells in the intestinal immune system, which protects you from attacks by pathogenic agents like bacteria and viruses. The intestine is the primary reservoir for immune cells in your body. For its part, the immune system influences the composition and diversity of microbiota.12

What affects your gut microbiota ?

The composition of the gut microbiota is characterized by its high diversity (number of different species present in an individual) and its abundance (total number of microorganisms present). When the composition is disrupted, the balance is broken, and a  (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) emerges,13 which can be associated with several diseases. 

Numerous factors can have an impact on the diversity and composition of the gut microbiota. Among these factors, these are the following:

Factors linked to the individual themselves, such as:

  • The age6
  • Genetics13 
  • Certain illnesses and injuries13 

Others factors are linked to the individual's environment:

  • Medication use: antibiotics, anti-inflammatories, etc.8 
  • Infections (viral gastroenteritis…)13
  • Lifestyle: unbalanced diet (high-fat diet for example), or changes in diet, stress, smoking, alcoohol excess, etc. 13

What are the diseases that could be linked to gut microbiota ?

Dysbiosis, cause or consequence of these diseases? The question has not yet been answered with certainty by scientific studies.

Let’s have a look to some diseases associated with intestinal dysbiosis:

  • Infantile colic 14 that affects 20 to 25% of infants between the age of 1 and 4 months

  • Antibiotics associated diarrhea, which happens between 5 and 35% of patients taking antibiotics15

  • Traveler’s diarrhea is an infection caused by contaminated food or contaminated. Postinfectious irritable bowel syndrome may occur in 3% to 17% of patients who had this infection16

  • Gastroenteritis generally benign and most often viral is responsible for over 200,000 deaths of children per year worldwide17

  • Obesity is a common, costly, and serious chronic disease that affected 13% of the world’s adult population (11% of men and 15% of women) in 201618

  • IBS is one of the most functional gastrointestinal disorders characterized by abdominal pain and alterations in the host’s bowel habits (constipation, diarrhea, or alternations). The prevalence varies substantially between countries19

  • Crohn’s disease is an inflammatory bowel disease, where inflammation can be localized at all stages of the digestive system, from the mouth to the anus. Recent studies provide evidence that the gut microbiota plays an important function in the etiopathogenesis of this disease20

  • Stomach cancer21 and colorectal cancer22 are two gastrointestinal cancers associated with gut microbiota dysbiosis

But the role of the human gut microbiota doesn’t stop at the gut: recent studies have identified that the gut microbiota may play a role beyond the gastrointestinal tract. In fact, gut microbiota has been associated with several extra-intestinal diseases: for example, acne23 , allergies24 , obesity,25 anxiety disorders,26 autism-spectrum disorders26…And that’s not all of it. It seems that gut microbiota can also be associated with neurodegenerative diseases like Alzheimer’s,27 Parkinson’s.28 In fact, there is bidirectional communication between the gut and the brain, named “gut- brain- axis”, and gut microbiota could influence these interactions. That is why your gut is sometimes called your second brain.

How to take care of your microbiota?

You know by now the central role of the gut microbiota in human health. So how should you take care of your own microbiota? How to improve your gut microbiota ? Many scientific studies raised the question of how to avoid any disruption in its composition and keep it as balanced as possible.29 The answer is not as simple as bring in good bacteria or yeast to fill or enrich the existing microbiota or replace the bad ones. In fact, the idea is to influence the microbiota to help it to function smoothly thereby improving host health.30

You have several ways of positively affecting the balance and the diversity of the gut microbiota :

  • Diet: the diversity and quality of what we eat contribute to the balance in our intestinal microbiota.31,32 On the other hand, a poorly balanced diet can affect the composition of our gut and lead to some conditions.33 It is important to know what type of food has a beneficial effect or a negative one to keep our gut in shape!34

  • Probiotics: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.35,36 

  • Prebiotics: Prebiotics are specific non-digestible dietary fibers conferring a health benefit, they are selectively utilized by beneficial microorganisms in the host’s microbiota.37,38 Some foods are particularly rich in prebiotics, that’s why it is important to pay attention to our diet. When they are added to probiotics in some specific products, we call them symbiotics.39

  • Transplant: as for the organs, gut microbiota can be transferred to an individual in an attempt to restore equilibrium amongst the gut microbial ecosystem.32 Known as fecal microbiota transplant (FMT), this therapeutic approach is only validated to cure recurrent Clostridioides difficile–associated disease32 and is still under active research to evaluate its effect on other specific health conditions such as Crohn's disease, ulcerative colitis, irritable bowel syndrome, or metabolic disease32

Oh! one more thing...

Now that you have read everything you need to know about the gut microbiota, you should also know that you have microorganisms all along the body: in your skin,40 your urinary tract,41 your vagina,42 your mouth,43 your ears,44 your lungs,45 and, as it does for the intestine, the microorganisms that live there play a tremendous role to keep them functioning and maintain you in health. To know more visit this page.

The Biocodex Microbiota Institute is dedicated to education about human Microbiota for General Public and Healthcare Professionals, it doesn't give any medical advice.
We recommend you to consult a healthcare professional to answer your questions and demands.

All the information in this article comes from scientific approved sources. Keep in mind this is not exhaustive. Here are all the studies from which we took all of that information

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Sources

1 Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006 Feb 24;124(4):837-48.

2 Ursell LK, Metcalf JL, Parfrey LW, et al. Defining the human microbiome. Nutr Rev. 2012;70 Suppl 1(Suppl 1):S38-S44.

3 Callaway E. C-section babies are missing key microbes [published online ahead of print, 2019 Sep 18]. Nature. 2019;10.1038/d41586-019-02807-x. 

4 Sandall J, Tribe RM, Avery L, et al. Short-term and long-term effects of caesarean section on the health of women and children. Lancet. 2018;392(10155):1349-1357.

5 Bäckhed F, Roswall J, Peng Y, et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of LifeCell Host Microbe. 2015;17(5):690-703.

6 Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012 May 9;486(7402):222-7.

7 Ragonnaud E, Biragyn A. Gut microbiota as the key controllers of "healthy" aging of elderly people. Immun Ageing. 2021 Jan 5;18(1):2. 

8 Jandhyala SM, Talukdar R, Subramanyam C, et al. Role of the normal gut microbiota. World J Gastroenterol. 2015 Aug 7;21(29):8787-803.

9 Tomas J, Wrzosek L, Bouznad N, B, et al. Primocolonization is associated with colonic epithelial maturation during conventionalization. FASEB J. 2013 Feb;27(2):645-55.

10 Caballero S, Pamer EG. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu Rev Immunol. 2015;33:227-56.

11Sokol H. Microbiota and barrier effect. In: Marteau P, Dore J, eds. Gut Microbiota: A Full-Fledged Organ. Paris: John Libby Eurotext; 2017:65-71.

12 Brandtzaeg P. Role of the Intestinal Immune System in Health. In:  Baumgart, Daniel C, eds. Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach. Springer International Publishing; 2017

13 Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.

14 Perceval C, Szajewska H, Indrio F, et al. Prophylactic use of probiotics for gastrointestinal disorders in children. Lancet Child Adolesc Health. 2019 Sep;3(9):655-662.

15 McFarland LV. Antibiotic-associated Diarrhea: Epidemiology, Trends and Treatment. Future Microbiol. 2008 Oct;3(5):563-78.

16 Steffen R, Hill DR, DuPont HL. Traveler's diarrhea: a clinical review. JAMA. 2015 Jan 6;313(1):71-80. 

17 Stuempfig ND, Seroy J. Viral Gastroenteritis. In: StatPearls. Treasure Island (FL): StatPearls

18 WHO. Fact sheets on obesity and overweight June 2021

19 Oka P, Parr H, Barberio B, et al. Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020 Oct;5(10):908-917. 

20 Aldars-García L, Marin AC, Chaparro M, et al. The Interplay between Immune System and Microbiota in Inflammatory Bowel Disease: A Narrative Review. Int J Mol Sci. 2021 Mar 17;22(6):3076.

21 Nasr R, Shamseddine A, Mukherji D, et al. The Crosstalk between Microbiome and Immune Response in Gastric Cancer. Int J Mol Sci. 2020 Sep 9;21(18):6586. 

22 Ranjbar M, Salehi R, Haghjooy Javanmard S, et al. The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review. Cancer Cell Int. 2021;21(1):194. 

23 Dreno B, Dagnelie MA, Khammari A, et alThe Skin Microbiome: A New Actor in Inflammatory Acne. Am J Clin Dermatol. 2020 Sep;21(Suppl 1):18-24.

24 Houghteling PD, Walker WA. From Birth to "Immunohealth," Allergies and Enterocolitis. J Clin Gastroenterol. 2015 Nov-Dec;49 Suppl 1(0 1):S7-S12

25 Ley RE, Turnbaugh PJ, Klein S, et al. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. 

26 Maiuolo J, Gliozzi M, Musolino V, et al. The Contribution of Gut Microbiota-Brain Axis in the Development of Brain Disorders. Front Neurosci. 2021 Mar 23;15:616883. 

27 Qian XH, Song XX, Liu XL, et al. Inflammatory pathways in Alzheimer's disease mediated by gut microbiota. Ageing Res Rev. 2021 Mar 9;68:101317.

28 Lorente-Picón M, Laguna A. New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules. 2021 Mar 15;11(3):433. 

29 ILSI Europe, 2013 Probiotics, Prebiotics and the Gut Microbiota. ILSI Europe Concise Monograph. 2013:1-32.

30 Quigley EMM. Prebiotics and Probiotics in Digestive Health. Clin Gastroenterol Hepatol. 2019;17(2):333-344.

31 Tap J, Furet JP, Bensaada M, et al. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults. Environ Microbiol. 2015 Dec;17(12):4954-64. 

32 Quigley EMM, Gajula P. Recent advances in modulating the microbiome. F1000Res. 2020;9:F1000 Faculty Rev-46. Published 2020 Jan 27.

33 Zmora N, Suez J, Elinav E. You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol. 2019 Jan;16(1):35-56

34 Wilson AS, Koller KR, Ramaboli MC, et al. Diet and the Human Gut Microbiome: An International Review. Dig Dis Sci. 2020;65(3):723-740. 

35 FAO/OMS, Joint Food and Agriculture Organization of the United Nations/ World Health Organization. Working Group. Report on drafting  guidelines for the evaluation of probiotics in food, 2002.

36 Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514.

37 Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics .J Nutr, 1995; 125:1401-12.

38 Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502.

39 Markowiak P, Śliżewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017;9(9):1021.

40 Bay L, Barnes CJ, Fritz BG, et al. Universal Dermal Microbiome in Human Skin. mBio. 2020;11(1):e02945-19. 

41 Neugent ML, Hulyalkar NV, Nguyen VH, et alAdvances in Understanding the Human Urinary Microbiome and Its Potential Role in Urinary Tract Infection. mBio2020 Apr 28;11(2):e00218-20.

42 Greenbaum S, Greenbaum G, Moran-Gilad J, et al. Ecological dynamics of the vaginal microbiome in relation to health and disease. Am J Obstet Gynecol. 2019 Apr;220(4):324-335.

43 Radaic A, Kapila YL. The oralome and its dysbiosis: New insights into oral microbiome-host interactions. Comput Struct Biotechnol J. 2021 Feb 27;19:1335-1360.

44 Xu Q, Gill S, Xu L, et al. Comparative Analysis of Microbiome in Nasopharynx and Middle Ear in Young Children With Acute Otitis Media. Front Genet. 2019;10:1176.

45 Mathieu E, Escribano-Vazquez U, Descamps D, et alParadigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma. Front Physiol. 2018 Aug 21;9:1168.

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Microbiota

The vaginal microbiota

The vaginal microbiota: how to take care of it?

Hundreds of bacteria populate the vagina.1 Let’s see how they work and why we should take care of our microbiota!

Vaginal microbiota

21% Only 1 in 5 women say they know exactly the meaning of the term “vaginal microbiota”

What is exactly the human vaginal microbiota?

The vaginal microbiota or vaginal flora consists of the hundreds of bacteria and the smaller number of fungi (Candida) that populate the vagina.1

For most women (and in contrast to the gut microbiota) the vaginal microbiota is balanced when its diversity is low (c. 200 bacterial species) and when lactobacilli – rod-shaped bacteria – predominate.1

All women have a vaginal microbiota, but every woman’s vaginal microbiota is different. To date, five main types of vaginal bacterial communities have been described:1,2

The vaginal microbiota is a dynamic community subject to the influence of factors that include ethnic origin, sex hormones, hormonal contraception, sexual behavior, vaginal douching, diet, smoking habits, social environment (e.g. living space) and genes.1,3

At the same time, the vaginal flora doesn’t live alone. The anus and the entrance to the vagina are located right next to each other and intestinal bacteria from the former can colonize the latter.4 The gut therefore constitutes a natural reservoir of lactobacilli for the vagina, which is important for the balance of the vaginal flora.5,6,7

How does the vaginal microbiota change throughout life?

The body evolves throughout life, and so does the vaginal microbiota. The vaginal microbiota’s composition changes greatly from childhood through adulthood to the menopause.1 Hormonal changes alter the rhythm of our lives, and impact the vaginal microbiota as well. For example, menstruation temporarily alters vaginal microbial diversity.8 The microbiota also plays a role in childbirth.1,10 During pregnancy, physiological changes occur to adapt the mother’s body to the fetus and vice versa.9 In pregnant woman, the vaginal microbiota is more stable, less rich and less diverse9, with high levels of estrogen ensuring the outright dominance of lactobacilli.1,8 Lastly, at menopause the vaginal microbiota settles into a new balance.10

Why is the vaginal microbiota a key factor in health?

The bacteria in the vaginal microbiota help maintain a healthy vaginal environment.1 Some of these bacteria, particularly lactobacilli, prevent pathogenic (sidenote: Microorganisms Living organisms too small to see with the naked eye. This includes bacteria, viruses, fungi, archaea, protozoa, etc., collectively known as ’microbes’. Source: What is microbiology? Microbiology Society. ) from establishing themselves in the vagina. A number of mechanisms have been proposed:

  • by producing lactic acid the microbiota promotes an acidic environment (pH ≤ 4.5) unsuitable for many pathogens11,12
  • defensive compounds produced by the microbiota, such as hydrogen peroxide (H2O2) or antibacterial substances (bacteriocins), attack alien bacteria, viruses and fungi11,12
  • the microbiota acts as a barrier, making it difficult for pathogens to establish themselves on the vaginal walls. The presence of lactobacilli accelerates the renewal of the epithelium, to which pathogens may try to attach themselves11,12
  • the microbiota facilitates the production by the vaginal epithelium of a protective mucus which keeps pathogens at bay11,12
  • by stimulating the woman’s immune system, the microbiota improves her ability to fight attacks by pathogens11,12

30% 3 out of 10 women know that the vaginal microbiota is balanced when its bacterial diversity is low.

An unbalanced vaginal microbiota: what are the associated diseases?

Stress, illness, excessive hygiene (douches), medication (antibiotic therapy, etc.), alcohol, tobacco… all of these factors can impact the composition of the vaginal microbiota.8,13 When the composition of the microbiota is unbalanced, we have what we call a “ (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) ”.8,11

A vaginal dysbiosis is when lactobacilli, the key bacteria in the vaginal flora, lose their predominance, paving the way for opportunistic microorganisms to colonize the vagina.8,11 Their presence is often associated with vaginal discharge, itching and burning, or a fishy smell, but can also be asymptomatic.8

A vaginal dysbiosis is associated to:

  • a bacterial vaginosis, due to colonization by pathogenic bacteria1
  • a candidiasis, due to the proliferation of a fungus8
  • reduced fertility11
  • a higher risk of premature birth1

Be aware

Bear in mind that women suffering from bacterial vaginosis are more likely to contract sexually transmitted infections (STIs), such as herpes, the papillomavirus, HIV/AIDS, or bacterial infections (gonorrhea, chlamydia, trichomonas).3,14

Knowing what has a direct impact on it, how can we take care of our vaginal microbiota?

Taking care of the vaginal microbiota is essential. Daily intimate hygiene is crucial to prevent dysbiosis. There’s much false information out there, so it’s important to understand the DO’S and DON’TS.

Daily:

While vaginal douching is not recommended since it alters the vaginal flora, external washing of the vulva with a suitable intimate gel15 helps reduce the unwanted accumulation of vaginal discharge, sweat, urine and fecal contaminants.16


To contribute to the good health of vaginal microbiota:

Hygiene is still necessary15, but it’s not enough. Several options for the vaginal microbiota already exist or are currently being tested:

  • Probiotics: Probiotics are live microorganisms that, when administered in appropriate amounts, confer health benefits on the host.17,18 They can reduce or safely correct microbiota imbalances. Probiotics for women administered either via the vagina or orally may help rebalance the vaginal flora, improve symptoms and reduce the risk of recurrence of various vaginal infection13,19,20,21. This is true both for women of childbearing age and postmenopausal women.13,20,21
  • Prebiotics: Prebiotics are specific non-digestible dietary fibers that confer a health benefit. They are selectively used by beneficial microorganisms in the host’s microbiota.22,23 When added to probiotics in specific products, they are known as symbiotics.24 Prebiotics for women are thought to promote the growth of lactobacilli and to help restore healthy vaginal acidity.19,25,26

That’s not all!

Recent studies have brought to light other therapeutic options for modifying the vaginal microbiota, such as vaginal microbiota transplantation (VMT). Inspired by fecal microbiota transplants, VMT involves grafting the vaginal microbiota of a healthy woman into women suffering from a vaginal dysbiosis. VMT is a promising option for refractory or recurrent bacterial vaginosis, although to date it has only been tested in a very small number of patients (5 in 2019).27

All the information in this article comes from scientific approved sources. Keep in mind this is not exhaustive. Here are all the studies from which we took all of that information.

International Microbiota Observatory

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Sources

1 Greenbaum S, Greenbaum G, Moran-Gilad J, et al. Ecological dynamics of the vaginal microbiome in relation to health and disease. Am J Obstet Gynecol. 2019 Apr;220(4):324-335.

Petrova MI, Lievens E, Malik S, et al. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. 2015 Front. Physiol. 6:81.

Lewis FM, Bernstein KT, Aral SO. Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases. Obstet Gynecol. 2017;129(4):643-654.

Petricevic L, Domig KJ, Nierscher FJ, et al. Characterisation of the oral, vaginal and rectal Lactobacillus flora in healthy pregnant and postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2012;160(1):93-99.

Reid G, Bruce AW, Fraser N, et al. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol 2001;30: 49–52.

Antonio MA, Rabe LK, Hillier SL. Colonization of the rectum by Lactobacillus species and decreased risk of bacterial vaginosis. J Infect Dis 2005;192:394–8.

Hilton E, Isenberg HD, Alperstein P, et al. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann Intern Med 1992;116:353–7

Amabebe E, Anumba DOC. The Vaginal Microenvironment: The Physiologic Role of Lactobacilli. Front Med (Lausanne). 2018 Jun 13;5:181.

Gupta P, Singh MP, Goyal K. Diversity of Vaginal Microbiome in Pregnancy: Deciphering the Obscurity. Front Public Health. 2020 Jul 24;8:326.

10 Petrova MI, van den Broek M, Balzarini J, et al. Vaginal microbiota and its role in HIV transmission and infection. FEMS Microbiol Rev. 2013;37(5):762-792

11 Younes JA, Lievens E, Hummelen R, et al. Women and Their Microbes: The Unexpected Friendship. Trends Microbiol. 2018 Jan;26(1):16-32.

12 Kovachev S. Defence factors of vaginal lactobacilli. Crit Rev Microbiol. 2018 Feb;44(1):31-39.

13 Riepl M. Compounding to Prevent and Treat Dysbiosis of the Human Vaginal Microbiome. Int J Pharm Compd. 2018 Nov-Dec;22(6):456-465.

14  Torcia MG. Interplay among Vaginal Microbiome, Immune Response and Sexually Transmitted Viral Infections. Int J Mol Sci. 2019;20(2):266.

15 Bohbot JM, Rica E. Microbiote vaginal, la révolution rose. Editions Marabout. 288 p.

16 Chen Y, Bruning E, Rubino J, et al. Role of female intimate hygiene in vulvovaginal health: Global hygiene practices and product usage. Womens Health (Lond). 2017;13(3):58-67.

17 FAO/OMS, Joint Food and Agriculture Organization of the United Nations/ World Health Organization. Working Group. Report on drafting  guidelines for the evaluation of probiotics in food, 2002.

18 Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514.

19 Gupta P, Singh MP, Goyal K. Diversity of Vaginal Microbiome in Pregnancy: Deciphering the Obscurity. Front Public Health. 2020 Jul 24;8:326.

20  de Vrese M, Laue C, Papazova E, et al. Impact of oral administration of four Lactobacillus strains on Nugent score - systematic review and meta-analysis. Benef Microbes. 2019;10(5):483-496.

21 Bohbot JM, Daraï E, Bretelle F, et al. Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence [published correction appears in J Gynecol Obstet Hum Reprod. 2018 Apr;47(4):177]. J Gynecol Obstet Hum Reprod. 2018;47(2):81-86.

22 Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics .J Nutr, 1995; 125:1401-12.

23 Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502.

24 Markowiak P, Śliżewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017;9(9):1021.

25 Collins SL, McMillan A, Seney S, et al. Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota. Appl Environ Microbiol. 2018;84(5):e02200-17.

26 Shmagel A, Demmer R, Knights D, et al. The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies. Nutrients. 2019 Jan 30;11(2):294.

27 Lev-Sagie A et al. Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nat Med. 2019 Oct 7.

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Clostridioides difficile: gut microbiota markers predict the risk of infection

A study conducted in six European countries has made it possible to identify the gut microbiota markers predictive of antibiotic-associated diarrhea and Clostridioides difficile infection. 

The gut microbiota Fecal transplant and recurrent Clostridium difficile infections: bacteriophages are necessary in donors Could the metabolome be used to better diagnose <em>C. difficile<em> infections? What are the long-term effects of antibiotics on the gut microbiota?

Dysbiosis caused by a course of antibiotics can lead to Clostridioides difficile infection. This pathogen is associated with significant morbidity and mortality, as well as high health care costs worldwide. Identifying markers of this infection could contribute to improving treatment and reducing the severity of infection.

More than 1000 patients recruited from 34 European hospitals.

In this observational, prospective, multicenter study, the gut microbiota of hospitalized patients aged over 50 years was analyzed (16S rRNA sequencing combined with an oligotyping technique for identifying C. difficile) the day before starting antibiotic therapy with the aim of identifying microbial markers predictive of antibiotic-associated diarrhea (AAD) and C. difficile infection (CDI). A longitudinal analysis was also performed to assess the impact of (sidenote: Penicillin + beta-lactamase inhibitor, other classes of beta-lactams, Fluoroquinolones )  on the gut microbiota.

Markers predictive of CDI

135 patients reported diarrhea in the 90 days following treatment, 15 of which had CDI. Researchers observed that the diversity of the microbiota on D1, prior to any antibiotic therapy, was lower in patients who had suffered CDI compared with those who had suffered AAD or patients who had not had diarrhea at all. The composition of their gut microbiota was also different: Enterococcus was more abundant, whereas there was a reduction in Blautia, Ruminococcus, Porphyromonas, Bifidobacteria, Odoribacter, Prevotella and Ezakiella spp. compared with patients who had not had CDI. Ruminococcus, Ezakiella and Odoribacter spp., five days prior to the onset of CDI in this cohort. These predictive markers were compared with those from a Canadian cohort of elderly patients who suffered CDI. In exactly the same way, the gut diversity was reduced; there was an increase in Enterococcus and a reduction in Ruminococcus, Ezakiella and Odoribacter spp. five days prior to the onset of infection.

Antibiotic-induced dysbiosis

The authors also found that antibiotics induced dysbiosis, which was classed as such six days after the start of treatment. The gut microbiota of patients taking beta-lactam antibiotics (a different class from penicillin) suffered the most disruption. All beta-lactams (regardless of whether they are combined with a beta-lactamase inhibitor or not) increase the abundance of Enterococcus. Treatment with penicillin combined with a beta-lactamase inhibitor was also associated with a reduction in bacteria belonging to the Clostridiales Incertae Sedis XI family, known for being associated with a reduced risk of CDI. The other classes of beta-lactams induced a reduction in bacteria belonging to Lachnospiraceae, including butyrate-producing species, known for their beneficial effects on health. Collectively, all the classes of antibiotics studied considerably altered the composition of the gut microbiota and are well documented, as they involve a high risk of developing CDI.

 

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The impact of contraceptives on the microbiota? Hit and miss!

Do hormones in female contraceptives harm the microbiota? According to science, it all depends on the flora in question: the lactobacilli-dominated vaginal microbiota seems to be protected but the gut microbiota is slightly disturbed. 

The vaginal microbiota

All women know that the hormonal fluctuations of the menstrual cycle influence, among other things, the vaginal flora and gut transit. So could female contraceptives, particularly those that work on hormones, modify, for better or worse, the dynamics of the vaginal and gut microbiota?

Oral contraceptives boost the vaginal flora...

The vaginal microbiota has a unique quality: it is in good health when its diversity is low and rod-shaped bacteria, lactobacilli, predominate. This contrasts with other microbiota, including the gut microbiota, which are considered in balance when highly diversified. The predominance of lactobacilli protects the vagina against infection, since lactobacilli release lactic acid (among other substances), which slows the proliferation of pathogens. However, where dominant lactobacilli are replaced by other types of bacteria and the vaginal flora loses its balance (dysbiosis), bacterial vaginosis can result. However, hormonal contraceptives (oral or vaginal) seem to reduce the risk of contracting this disease.1 How? By boosting the lactobacilli! The estrogens contained in these contraceptives result in large quantities of glycogen being deposited on the vaginal walls. Glycogen is the favorite food of lactobacilli and allows the bacteria to multiply and produce more lactic acid. What about other types of contraception? Although research in this area is still limited, the vaginal ring does not seem to cause any substantial modification of the vaginal flora, while IUDs (whether copper or hormonal) appear to have no effect.1

...but slightly disturb the gut microbiota

Unlike the vaginal microbiota, a healthy gut flora should be diverse. However, the pill artificially maintains constant levels of estrogen and progesterone in the blood, which appears to disturb the gut microbiota. In a recent study involving 16 healthy premenopausal women2, oral contraceptives were associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. However, it is not yet known whether the hormones in the pill have a direct effect on the gut microbiota or whether they work indirectly via other physiological processes that themselves affect the bacteria in the gut. Despite this, these preliminary results show that the pill may affect women’s health. Hence the need for further studies to gain a more complete understanding of the impact of these drugs on the gut microbiota.

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Modulating the gut microbiota to better fight child malnutrition

Long before the advent of genetics, more traditional analytical methods already showed that the bacterial communities of the gut were different in children who suffered from severe malnutrition. What if restoring good gut bacteria could influence these children’s growth?

The gut microbiota Diet

Delayed growth, long-term consequences on the metabolism, immunity, and cognitive development… malnutrition in children is still a global health problem, with therapeutic and food-related solutions that are still incomplete or even insufficient. Researchers have realized that the gut microbiota of these children has maturation deficits, with seemingly underdeveloped microbial communities compared to those of healthy children. The aim of this study, which steers away from the norm, is to concentrate on the gut microbiota in order to influence growth, and to see how a food supplement that targets gut microbiota (MDCF-2) improves the growth of 118 malnourished Bangladeshi children versus a pre-existing ready-to-use supplementary food (RUSF).

Children who grow and put on weight more quickly

Although RUSF has more calories, the children who received MDCF-2 gained more weight and grew more quickly. In addition, children who received MDCF-2 presented with higher levels of proteins associated with bone growth and neurological development. Another encouraging result: 21 types of bacteria that are positively linked with changes in growth were detected.

Hope for millions of children?

To date, over 30 million children under the age of five years still suffer from malnutrition world-wide. This study suggests that the healthy growth of children is inexorably linked to optimal development of their gut microbial communities after birth. Larger studies conducted in more varied geographical areas should make it possible to confirm the advantages of a nutritional therapy that targets the gut microbiota compared with traditional strategies. Confirmation of these therapeutic claims would mark a significant success in the fight against the consequences of child malnutrition.

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Chen RY, Mostafa I, Hibberd MC, et al. A Microbiota-Directed Food Intervention for Undernourished Children. N Engl J Med. 2021;384(16):1517-1528.

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Malnutrition: acting on the microbiota in order to improve growth, a trial prototype

A new study, published in The New England Journal of Medicine, showed that during a randomized clinical trial, a therapeutic food supplement created for restoring the gut microbiota of children suffering from malnutrition was better than the standard therapy for maintaining their growth.

The gut microbiota Could fibers modify the microbiota? The gut microbiota has a specific signature for fibromyalgia The microbiota as a barrier against rotavirus
Actu PRO : Malnutrition : agir sur le microbiote pour améliorer la croissance, un prototype à l’essai

Over 30 million children aged under 5 years suffer from (sidenote: Moderate Acute Malnutrition (MAM) Defined by the World Health Organization as a weight/height ratio two to three standard deviations lower than the median of the age cohort )  world-wide. The main characteristic of this global scourge is that these children have an immature gut microbiota (GM). During a (sidenote: Raman AS, Gehrig JL, Venkatesh S, et al. A sparse covarying unit that describes healthy and impaired human gut microbiota development. Science. 2019;365(6449):eaau4735. ) , the authors of this study defined a prototype food supplement (MDCF-2), which made it possible to restore the GM of children aged 12 to 18 months suffering from MAM. This new study aims to confirm the efficacy of MDCF-2 in children suffering from MAM in a larger study conducted over a longer period of time.

An interventional study conducted on 123 Bangladeshi children

In this randomized, controlled trial, 123 Bangladeshi children (12 to 18 months old) suffering from MAM received either MDCF-2 supplementation (204 kcal per daily dose of 50 g), or an existing ready-to-use supplementary food (RUSF, 247 kcal per daily dose of 50 g) twice a day for three months, followed by a one-month follow-up. At the same time, the team of researchers monitored weight, height, and arm circumference on a weekly basis, and also took blood and stool samples regularly.

Faster growth, more weight gain

Of the 118 children who completed the study (59 in each group), those in the MDCF-2 group had grown more rapidly than those in the RUSF group. For the children in the MDCF-2 group, the mean weekly variation in the weight-for-height index was 0.021, versus 0.010 in the RUSF group. As for weight-for-age, the mean weekly variation was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The variations in arm circumference and height-for-age index were similar in both groups.

Blood and intestinal biomarkers identified

After supplementation with MDCF-2, 714 proteins were significantly modified, versus 82 in the RUSF group. Although some of them were associated with musculoskeletal and nervous system development (p<0.001), 70 were also correlated with the weight-for-height index. On the other hand, proinflammatory markers, accentuated by malnutrition at the start of the study, were more largely reduced by MDCF-2 supplementation. With regard to the microbiota, MDCF-2 supplementation made it possible to significantly increase 21 bacterial taxa positively associated with the weight-for-height index (p<0.001) and inversely, to reduce two bacterial taxa (Escherichia coli and a species of Bifidobacterium) negatively associated with the weight-for-height index (p<0.001).

This study backs the following statement: adequate calorie and nutritional supply is insufficient for remedying the consequences of long-term malnutrition. According to the authors, optimal maturation of the GM is a priority. In order to evaluate the efficacy of this new therapeutic approach, larger studies are needed, which should be conducted in different geographical locations and in a broader pediatric age bracket.

 

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The oral microbiota and old age: a fresh start with a glass of nitrate-rich beetroot juice

Vegetables and beetroot juice: the best way to boost oral bacteria beneficial to vascular health and cognitive function! Would you like another glass?

The ENT microbiota Diet
Actu GP : Microbiote oral et grand âge : un jus de betterave - et des nitrates -, et ça repart ?

We all know how vegetables are good for us when it comes to nutrition, digestion, hydration, and reducing stress, but with this new discovery their benefits seem endless: the winning combination of nitrates and their effects on our oral bacteria. Like many other vegetables, beetroot is rich in inorganic nitrate, which is transformed by the oral bacteria into nitrite and then nitric oxide (NO). NO is beneficial to the health of our arteries and our grey matter. The only problem is that NO production diminishes with age. Could a glass of nitrate-rich beetroot juice help roll back the years?

Ten days of nitrate-rich beetroot juice for an oral microbiota in top form

This supplementation has fast-acting effects: a study has shown that consuming beetroot juice for ten days was enough to considerably modify the oral microbiota of about thirty Icelanders aged 70-80. Consuming the nitrate-rich juice influenced a number of bacterial groups in their oral microbiota. Specifically, there was a decrease in certain bacteria associated with inflammation (Prevotella and Veillonella) and in the dreaded Clostridium difficile, which can infect the gut and cause diarrhea. Conversely, other bacteria became relatively more abundant, such as a group comprising Neisseria and Haemophilus, both of which are associated with periodontal health, younger age, lower BMI, and abstinence from smoking.

Blood pressure down, attention up, morale excellent

Nitrate supplementation via beetroot juice reduced average blood pressure in participants. High blood pressure is a risk factor for cognitive decline. In this study, a reduction in blood pressure went hand in hand with an increase in certain bacteria (Streptococcus and Rothia) whose presence increases following absorption of the juice. Moreover, nitrate-rich beetroot juice also proved beneficial to cognitive health. However, the participants in the study were active and healthy seniors whose blood pressure was generally good. It remains to be seen whether this beneficial effect can be reproduced in other age groups and in people in poorer health. In the meantime, we should all include as many vegetables as possible in our meals and smoothies!

 

Sources

Vanhatalo A, L'Heureux JE, Kelly J et al. Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions. Redox Biol. 2021 Mar 5;41:101933.

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The role of the vaginal, uterine and gut microbiota in endometriosis

Cause or consequence? While this is a difficult question to answer, it appears that the gut and reproductive tract microbiota of women suffering from endometriosis are involved in the development of this serious disease.

The vaginal microbiota Vaginal microbiota: a marker for papillomavirus progression? Using recombinant endolysins to treat bacterial vaginosis Vaginal microbiota and predisposition to candidiasis

Endometriosis (EMS) is an inflammatory disease characterized by the presence of endometrial tissue outside the uterine cavity. Different studies suggest a prevalence for the disease of between 6% and 15% for women of reproductive age. EMS can cause severe primary dysmenorrhea, reduced infertility, and pelvic mass, seriously affecting women’s quality of life. The pathogenesis of EMS is still poorly understood, but the microbiota may be involved. Certain hypotheses blame inflammatory endotoxins found in the peritoneal cavity, such as bacterial lipopolysaccharide (LPS). These inflammatory endotoxins could regulate the pro-inflammatory reaction and promote the growth of endometriosis.1

Vaginal lactobacillus diminished

To further investigate the “bacterial contamination hypothesis”, a team collected microbiota samples from along the reproductive tracts of 36 women with endometriosis and 14 controls who had undergone surgery for a benign gynecological tumor. The results? An increasingly pronounced dysbiosis as one moves up the reproductive tract, a decrease in Lactobacillus in the vaginal flora which becomes more pronounced as one moves up towards the endometrium, and specific (sidenote: Operational Taxonomic Unit groups of organisms usually not cultivated or not identified, classified on the basis of the similarity of the DNA sequencing of a given gene. Frequently used as an equivalent to the concept of species )  in the cervical mucus which increase in the upper genital tract (endometrial samples and peritoneal fluid). This alteration of the microbiota all along the reproductive tract suggests that certain bacteria may be involved in the pathogenesis of EMS.

Role of the gut microbiota?

EMS is far from being limited to gynecological symptoms: up to 90% of patients report gastrointestinal symptoms as well.2 Two studies, one in Sweden2 (66 EMS patients, 198 matched controls) and the other in Shanghai3 (12 EMS patients with moderate to severe forms of the disease, 12 controls), examined the link between the gut microbiota and EMS: (sidenote: Beta diversity Rate of variation in species composition, calculated by comparing the number of unique taxa in each ecosystem ) , and to a (sidenote: Beta diversity Rate of variation in species composition, calculated by comparing the number of unique taxa in each ecosystem ) , diversity of the EMS patients’ flora was found to be lower than that of the controls. In addition, the abundance of bacterial taxa differed. In the Chinese study, Prevotella was dominant among the EMS patients, while Coprococcus prevailed among the controls. Additionally, the gut microbiota of the EMS group was enriched for certain microbial function categories (environmental information processing, endocrine system, and immune system). Serum levels of hormones (particularly estradiol) and inflammatory factors (notably IL-8) were significantly higher in the women with EMS.3 Lastly, correlations were detected between the abundance of both Blautia and Dorea and estradiol level, and between Subdoligranulum abundance and IL-8 level.3 Thus, there are associations between the gut microbiota and both serum hormones and inflammatory factors in EMS.

Estrogen or inflammatory etiology?

EMS is an estrogen-dependent disease2 and EMS patients generally have high estrogen levels in the serum.3 The gut microbiota, including Ruminococcaceae and Clostridia, may affect estrogen levels in the serum by modulating the reabsorption of estrogen excreted in the bile which eventually enters the gut.3 Other authors suggest a regulatory role for the gut microbiota in inflammatory processes outside the gastrointestinal tract.2 In other words, although correlations have been observed and hypotheses suggested, the actual mechanisms involved have not yet been elucidated. Nevertheless, these three studies highlight the involvement of the microbiota of the reproductive and digestive tracts in EMS, giving hope for an improvement in the diagnosis and management of the disease.

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