A leading cause of blindness, kidney failure, stroke, and amputations¹, diabetes is a serious disease that happens when the pancreas does not produce enough insulin (type 1 diabetes²) or, in the majority of cases, when the body develops a resistance to the hormone (type 2 diabetes, T2D³).  Faced with a fourfold rise in the number of cases over the past 40 years, with over 420 million people now affected around the world1, public authorities and international organizations are taking action to improve access to care. On November 14, every year since 1991, World Diabetes Day aims to raise awareness of the disease.

Microbiota specific to T2D...

Faced with these facts, researchers are doing everything they can to work out not only the causes of the disease, but also how to prevent it. An increasing amount of attention is being paid to the gut microbiota. And for good reason, since several studies have spotted a link between its composition and the risk of T2D. Most recently, researchers brought out the big guns and managed to assemble over 2,000 subjects (compared with just a few hundred for previous studies) to compare the microbiota of people with and without diabetes.

...with changes evident even at the early stages

The results are enlightening: T2D is less common in people whose microbiota is diverse and rich in certain bacteria able to produce a particular short-chain fatty acid (SCFA) known as butyrate (sidenote: SCFAs Short Chain Fatty Acids are a source of energy (fuel) for the cells of the individual. They interact with the immune system and are involved in the communication between the intestine and the brain. Sources:
Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) , which is beneficial for metabolism and cell activity, and has anti-inflammatory properties. But the researchers went further still and demonstrated, for the first time, that these people are also less affected by insulin-resistance (sidenote: Insulin-resistance An altered response of cells to the action of insulin (a hormone that helps the body use sugar for energy), insulin resistance results in poor regulation of blood sugar levels. Sources
Inserm. La résistance à l’insuline, une histoire de communication. 2018. 
Centers for disease control and prevention. Diabetes - Resources and Publications -Glossary  ) , a phenomenon that appears very early on in the development of T2D. The bottom line? There are telltale signs in the microbiota even at the very early stages of development of the disease.

These results are very promising and provide a new insight into our understanding of the factors involved in the pathogenesis of diabetes. Better still, they could pave the way for new targeted treatments for the rising number of patients.

Even though some studies had already made a link between the intestinal microbiota and type 2 diabetes (T2D), they were limited by a small sample size and there was ongoing debate as to the exact taxonomic units involved (results not always reproducible, insufficient power, etc.) This is why researchers decided to embark upon a large-scale study of 2,166 subjects taken from two Dutch cohorts, to investigate links between the composition of the intestinal microbiota (analyzed using bacterial 16S RNA gene sequencing and amplification on fecal samples) and T2D (verified by two physicians using WHO criteria (blood glucose, use of anti-diabetic drugs, etc.).

Even though it used a cross-sectional design (i.e., data about the microbiota and T2D collected at the same time), the analyses were adjusted for several confounders, such as energy intake, body mass index, education level, etc. Another strength and novel aspect of the study was the investigation of links between the microbiota and insulin resistance (IR), measured using fasting insulin and blood glucose, a significant subclinical parameter indicating an early stage in the pathogenesis of T2D.

Does a diverse microbiota strengthen protection?

Several indicators of microbiota α-diversity (sidenote: α diversity A measure indicating the diversity of a single sample, i.e. the number of different species present in an individual. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej200997 ) were linked to lower IR and a reduced prevalence of T2D. In turn, β-diversity (sidenote: β diversity A measure indicating the species diversity between samples, it allows to assess the variability of microbiota diversity between subjects. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej20099 ) was linked to IR. Finally, an abundance of seven taxonomic units - belonging to the Christensenellaceae and Ruminococcaceae families and the genus Marvinbryantia - were linked to a lower risk of IR, and an abundance of five other taxa - the Clostridiaceae and Peptostreptococcaceae families, and the genera Clostridium sensu stricto, Intestinibacter and Romboutsia – to a lower risk of T2D.

Butyrate-producing taxa that reduce the risk of T2D

These 12 taxonomic units, 10 of which have been linked for the first time to a lower risk of T2D or IR, are known to produce butyrate, a short-chain fatty acid produced by the breakdown of dietary fibers by bacteria. Enhanced mitochondrial activity, improved energy metabolism, and reduced endotoxemia and inflammation are some of the mechanisms put forward to explain these effects. However, ad hoc studies are still needed to validate its role in glucose metabolism and the prevention of diabetes.

Nevertheless, the links that have been identified between, on the one hand, microbiota diversity and an abundance of butyrate-producing bacteria, and on the other hand, a lower risk of IR and T2D, shed further light on the etiology, pathogenesis, and treatment of type 2 diabetes.

As soon as we look into the minuscule world that resides in our body, certain words tend to pop up. Such words are not always clearly defined or appropriately used. Some definitions are therefore necessary.

From the ancestral term “flora”...

The term “flora” has certainly been around the longest. It once generally referred to the digestive system (the “gut flora”) and denoted, according to the Larousse medical dictionary, the “collection of microorganisms that normally resides in the intestine”. At that time, it was thought that the gut flora contained mainly bacteria¹. So when the term “flora” was used, it generally referred to the bacterial population living in the gut.

... to the contemporary term “microbiota”

As science progressed, this view of the flora proved to be far too simplistic. On the one hand, our digestive system hosts far more than bacteria. Viruses, fungi (including yeasts), and parasites also make it their home².

(and no, urine isn’t sterile!)  all have their own flora.…³

Little by little, another term, “microbiota”, has come into use. This term unambiguously refers to all communities of microorganisms (and not only bacteria). “Microbiota” is always accompanied by an adjective that specifies its location (skin microbiota, oral microbiota, etc.), since each microbiota has its own characteristic set of microorganisms.

And what about “microbiome”?

Sometimes the difference hangs on thread, or rather a couple of letters. Indeed, just two letters separate “microbiota” from “microbiome”. And yet these two terms are false friends. The first denotes the population of bacteria, viruses, etc., residing in a specific area of our body but the second refers to something completely different: the genetic material of this community taken as a whole, in other words everything that the microorganisms residing there know how to do (produce specific molecules, make specific types of membrane). Imagine putting all the microorganisms that make up a microbiota into a blender, thereby erasing their individual identity, and only being left with the genetic material of the resulting microbial soup. In a village, the “microbiote” would be the list of inhabitants and the “microbiome” the list of what these inhabitants collectively know how to do (make bread, build a house, etc.).
 

December 1 is World AIDS Day. To mark the occasion it's worth bearing in mind that the human immunodeficiency virus (HIV) attacks specific white blood cells called CD4+ T cells. The weakening of the immune system allows opportunistic infections, cancer, and other diseases of the organs to develop. Today, antiretroviral therapy can restore CD4+ T cell counts and lower the viral load to undetectable levels. Unfortunately, this does not protect against all of HIV's adverse effects. Inflammation of the oral cavity is particularly common HIV-infected individuals and is often associated with an imbalance in the oral microbiota.

Gut imbalance plays role in immune response to infection

HIV activates the CD4+ T cells, which then exhaust themselves trying to fight the virus. The virus eventually destroys the cells or prevents them from functioning properly. In addition, the gut microbiota loses its balance, (dysbiosis), with certain beneficial bacteria (such as lactobacilli (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. ) ) becoming less abundant, while other species, including some pathogens (sidenote: Pathogen 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. ) , proliferate. The infection also attacks the intestinal mucosa, which loses its impermeability, and releases its contents. This causes inflammation to spread throughout the body, damaging the organs. The result is a vicious circle, with inflammation driving HIV replication. Early antiretroviral therapy preserves the integrity of the intestinal mucosa and the balance of the gut microbiota. However, it does not prevent the persistence of inflammation, which is likely to increase the risk of oral disease.

HIV and oral diseases: initial hypotheses and solutions

Why does HIV infection weaken the oral mucosa and increase the risk of oral diseases, even when controlled by treatment? One possible explanation is that HIV impairs the production of secretory immunoglobulin A antibodies in the saliva, which are considered the first line of defense against oral pathogens. It may also be because the loss of CD4+ T cells, as in the gut microbiota, results in inflammation and oral dysbiosis. However, few studies have analyzed the oral microbiota composition of HIV-infected individuals and the results of such studies are not always consistent. In addition, it is currently very difficult to assess the impact of the virus itself, versus that of the treatment, on oral bacterial communities.

The authors conclude that further research is needed on the interrelationships between the oral microbiota and oral mucosal immunity (sidenote: A scientific review published in September 2021 provides an update. ) . Such research is essential to the discovery of therapies that relieve the distressing oral symptoms of HIV. "Probiotic" approaches have already been proposed for the prevention of oral diseases. One example is the displacement of one bacterial strain that causes cavities with another that is engineered to have low pathogenicity. Well-conducted clinical trials are now needed to assess the efficacy of using probiotic strains and antimicrobial agents to improve oral immune functions.

Gut microbiota maturation begins immediately after birth. This maturation continues through the first few years of life, in parallel with that of the immune system. Gut microbiota maturation and immune development are both implicated in allergic diseases, with prenatal factors suspected in each case. Meconium, the first stool of an infant after birth, contains metabolites produced in utero. It reflects perinatal influences, since it begins forming by gestational week 16, while it also contains the starting material for the initial microbiota. Hence this study attempted to link metabolic signatures within the meconium, microbiota maturation and immune system development.

Less maturation, more atopy

After analyzing (via 16S rRNA sequencing) stool collected at 3 months and 1 year from 950 children in the Canadian CHILD (sidenote: Canadian CHILD Cohort Study Canadian Healthy Infant Longitudinal Development study, a prospective study of children recruited before birth between 2008 and 2012 ) cohort, the researchers made a first discovery: the gut microbiota of the future allergic children was less mature, even before the appearance of the atopy. Thus, the 212 infants who subsequently developed atopy at 1 year of age had a less mature microbiota at 3 months than those who did not become atopic. The relative abundance of 13 of the 15 taxa most involved in maturation of the microbiota was lower in atopic infants.

Influence of prenatal exposures

To understand the origin of this difference in maturation, the researchers went back in time and analyzed meconium samples in a subgroup of 100 children. They observed lower bacterial diversity in the future atopic children. Metabolic diversity was also reduced, with fewer molecules associated with the metabolism of amino acids, vitamins and hormones. This suggests that differences influencing the development of the microbiota and, ultimately, immune development, exist from birth. Thus, atopy at 1 year of age is associated both with a metabolically less rich meconium at birth and with a reduction in the diversity and maturation of the microbiota at the beginning of life. A potential mechanism of action is suggested: meconium metabolites, which reflect prenatal exposures, may be metabolized and fermented by bacteria. Thus, the gut microbiota at the beginning of life, and ultimately immune development, would be impacted by intrauterine life.

Meconium is not sterile:

Prevent... and predict?

A better understanding of the prenatal determinants of meconium composition, and of the direct and indirect effects of its metabolites on immune development and bacterial colonization in newborns, may ultimately help prevent the development of allergies. It may even allow us to predict – via metabolic signatures – the risk of developing allergies, even if the researchers’ first studies (combining meconium data and clinical data from mother and child) gave results that are certainly encouraging but still far from precise.

The gut microbiota is the most well-known of the body’s microbiota. However, the body hosts many other microbial ecosystems, each of which receives considerable attention in scientific publications and the media. Each new study shines further light on the decisive role they appear to play in our health. Let’s take a closer look at this vast “network”.

Human microbiota: a community of microorganisms...

The human microbiota is made up of the set of microorganisms – mainly bacteria, but also viruses and fungi – that live in our body. The vast majority (70%) are found in the digestive system, which is home to 1.5 kg of bacteria. But five other organs also host (sidenote: Host The body provides food and shelter to the microorganisms that colonize it.  ) a microbiota: the skin, mouth, lungs, urinary tract, and genitalia. The microorganisms in the microbiota are symbiotic (sidenote: симбиотические Тесная и взаимовыгодная связь между двумя или более организмами ) . We provide them with the necessary conditions for survival and in return they contribute to the proper functioning of our body (digestion of food, protection against infection, synthesis of vitamins). A win-win situation! A balanced microbiota helps ensure good health. On the other hand, an unbalanced microbiota – or dysbiosis – is conductive to numerous diseases.  

... within a network of interconnected ecosystems

At first glance, the body’s various microbial ecosystems appear to influence only their respective host organ. However, numerous studies have shown that an imbalance in one organ can have an impact on the others. For example, a disturbed gut microbiota has been linked with certain diseases of the skin (dermatitis, psoriasis) or lungs (asthma, chronic bronchitis, cancer), while poor oral hygiene increases the risk of developing lung infections. The latest scientific research suggests that these different ecosystems form an interconnected network with the gut at the center. Gut-brain axis, gut-skin axis, gut-lung axis, gut-mouth axis, gut-liver axis... and so on. The gut channels information and acts as a relay with peripheral ecosystems.

Promising implications for research and medicine

Research on the microbiota is still in its infancy. To confirm the hypothesis of an interconnected network of microbiota centered around the digestive system, more research is needed on the microbiota as a whole. Despite this, the applications in medicine seem promising: by restoring the balance of one ecosystem, it may be possible to modify the balance of another, thus leading to innovative treatment strategies.

Recommended by our community

The human microbiota is known to play a key role in host health. It is distributed between the digestive tract (70% of human microbiota), skin, lungs, mouth, urinary tract, and genital tract. These microbiota appear to be compartmentalized, hosting different microorganisms. However, a dysbiosis at one site appears to have remote consequences, leading to metabolic, inflammatory, immune, neoplastic, cognitive, degenerative, and genetic disorders. The authors of this review analyzed the communication axes between the various human microbiota with the aim of exploring the link between dysbiosis and illness.

Microbiota: communication axes centered around the gut?

Mechanisms of communication between microbiota

Several non-exclusive mechanisms may explain the connections between the various microbiota:

• Systemic diffusion of immunomodulatory metabolites from dietary fiber fermentation, particularly short-chain fatty acids (SCFAs). These metabolites may reach other microbiota through the bloodstream. For example, an accumulation of SCFAs in the respiratory tract may be responsible for lung inflammation and major susceptibility to allergens. 
• Systemic circulation of bacterial fragments, including extracellular bacterial vesicles. 
• Migration of entire bacteria:
  • Due to contiguity (e.g. between oral cavity and respiratory tract, or between urinary and genital tracts).
  • Through systemic passage where epithelial barriers lose integrity (particularly translocation to digestive tract).

They might look and read like scientific articles and journals, but they are not worthy of the name. Two evils are currently plaguing the world of scientific publication: “bogus” journals and “fake” articles.

Predatory journals

The principle of predatory journals is simple: they publish articles because they are paid by the authors and not because of the articles’ quality. This allows authors to publish lackluster findings unworthy of publication. It also allows interest groups to promote studies they know to be biased or falsified in order to promote the product or the sector they represent (e.g. a drug). The problem is that these predatory journals closely resemble legitimate journals, at times even partially plagiarizing their names, making it difficult to recognize them. The resemblance is so close that good scientists are being fooled into publishing legitimate articles in these journals, or are being influenced by the bad articles they read in them. Fortunately, lists of these predatory journals (more than 14,000 titles as of the beginning of 2021) can be found online, published by researchers and associations (such as predatoryjournals.com) constantly on the lookout for them.

Paper mills

In addition to fake journals, there are also fake articles. Such articles are written by paper mills, whose role is to provide authors in need of inspiration or career advancement with ready-made articles in return for a few dollars. The problem is that these articles contain fabricated scientific results and error-filled data. One can occasionally read articles on cancer, for example, whose data are pure science fiction, and this even in highly respected journals, whose editors have been duped.

Elisabeth Bik, a Dutch microbiologist specializing in scientific integrity (and in microbiota!) has identified over 400 fake research papers published in China by just one such paper mill¹. Even with researchers constantly on the lookout for these black sheep of the scientific publishing world, caution is still required, as anyone can be deceived. Aware of such scams, the Biocodex Microbiota Institute takes the greatest possible care in selecting the articles featured on its website.

The publication of scientific articles allows researchers to share their findings. A peer review system guarantees the quality of published work. Every article in a scientific journal worthy of the name has been previously reviewed by other experts in the field. Among other things, these experts can request improvements from the author or even refuse publication if they consider the article to contain errors or to be of little interest.

Predatory journals

However, some scientific journals are scientific in name only. Known as predatory journals, their principle is that the author pays to be published, whatever the quality of their article. The problem is that the researchers are at times fooled themselves, either as authors (some non-predatory journals ask for a contribution to publication costs) or as readers of such articles, which they believe to be correctly reviewed by peers. American library scientist, Jeffrey Beall, first denounced such journals^1,2 in 2012. He proposed a number of criteria to identify them (e.g. articles accepted too quickly) and drew up a list of culprits³. Since then, several groups have taken up the torch, among which predatoryjournals.com. To reveal the extent of such practices, some authors have gone so far as to submit bogus articles. For example, in exchange for $55, a team of Franco-Swiss authors was able to publish in one such journal a nonsense article co-signed by fictitious authors from non-existent institutes (Institute for Quick and Dirty Science), with absurd methodologies, wild conclusions (enriching table salt with hydroxychloroquine to reduce scooter accidents), and a bizarre bibliography.

Paper mills

As if bogus journals were not enough, a second scourge is also eating away at scientific publishing: paper mills. Paper mills provide authors lacking inspiration, time or ethical values, but who wish to boost their careers in return for money, with ready-made articles containing data produced from thin air. Since these articles may be published in mainstream (rather than predatory) journals, it is sometimes difficult to identify them. The scam may have reached industrial scale, involving thousands or tens of thousands of articles.⁴

Fightback underway

With the help of volunteer scientific investigators, such as microbiologist Elisabeth Bik⁵, the scientific community is preparing to fight back against this second scourge. Searching for images too similar to be true, in 2020, Bik’s blog⁶ identified more than 400 articles that were likely produced by a single Chinese paper mill. Iran and Russia were also singled out for blame. As a result, the publishers are reviewing the articles flagged, with many already retracted and others marked with “expressions of concern”⁷. Serious publishers are also becoming more careful about new submissions, not hesitating to ask authors for raw data to ensure the veracity of the studies performed.

Skin and gut dysbiosis, as well as immune dysregulation, have been observed in the development of atopic dermatitis, a complex disease with multifactorial causes.⁸