Despite progress regarding prevention, dental caries or cavities remain one of the most common afflictions in the world. They are formed when acid attacks the tooth enamel following the fermentation of dietary sugars by microbes found in dental plaque. While pathogenic bacteria implicated in this process are well known, the role of fungi contained in oral microbiota is not fully understood.

Candida dubliniensis is associated with cavity severity

To better understand how microorganisms interact to form a cavity, an American research team investigated dental plaque microbiota at different stages of cavity development. Their study, published in the review Applied and Environmental Microbiology, included 33 children with varying cavity status: some had no cavities, others had a few cavities which were attacking the enamel, others had cavities which had reached the dentine.

The authors identified 139 species of fungi. The two most abundant belonged to the Candida family: Candida albicans and Candida dubliniensis. They observed that composition of dental plaque microbiota varied significantly depending on cavity status, with an overabundance of 4 species in children with cavities and of 12 other species in children with healthy teeth. More specifically, the content of C. dubliniensis was directly correlated to cavity severity. Some of the beneficial species were able to mitigate the role of Staphylococcus mutans in tooth decay (a bacterium implicated in cavity formation) via the production of xylitol and antimicrobial compounds.

New therapeutic perspectives?

C. dubliniensis is known to play a role in cavity progression and severity and could be a good risk predictor for dental caries, concluded the authors. Their work should open up new preventive and therapeutic perspectives for dental caries.

Reduced risk of premature birth, improvement of maternal mood, better development of the brain, vision, motor skills, heart and immune system in newborns: the consumption of omega-3 oils (naturally present in salmon, mackerel, eggs, spinach, avocado and more) is favorable to the health of both mothers and their babies! This is why health authorities recommend that pregnant women consume between two and three portions of fish per week. This upper limit is fixed because of the risks associated with ingestion of mercury, found in varying quantities in fish. What is the impact of this dietary recommendation on the gut microbiota of newborns?

A microbiota affected by the maternal diet

To find out, a team of researchers analyzed stool samples from around one hundred babies aged around 4 months on average. Their results revealed three gut microbiota profiles: one dominated by bifidobacteria–also the richest and most diverse, one dominated by Escherichia spp., and the last by another specific bacterium, i.e. Enterobacter. Infants whose mother followed the dietary recommendations during the third trimester (at least 2 portions of fish per week) were up to 5 times more likely to have a microbiota dominated by bifidobacteria than by Escherichia. Could this protect them against certain diseases? It is possible, according to certain studies indicating that a microbiota with a low content of bifidobacteria is associated with irritable bowel syndrome, inflammatory bowel disease, celiac disease, and more.

Validity of the dietary recommendations

The authors consider that this study confirms the validity of dietary recommendations regarding consumption of fish during the third trimester of pregnancy–a critical period for brain development–revealing a benefit unknown until now. According to the authors, understanding the impact of the maternal diet on the infant gut microbiota should help better define the dietary recommendations for pregnant women.

The relationship between asthma and the microbiota in the respiratory tract of asthmatic children is still poorly understood. A prospective study analyzed the links between the relative abundance of bacteria in 319 nasal samples collected at two points in time–with asthma under control and at the onset of an attack–and asthma attacks suffered by 254 school-age children with Stage 2 asthma, 75.7% of whom experienced an attack during the 320 days of follow-up (with two attacks for 43.4% of the children included in the follow-up period).

Bacterial groups linked to asthma risk

The results show that the risk of attack or exacerbation varies according to the type of bacteria colonizing the nasal tract. Specifically, microbiotas in which the Corynebacterium and Dolosigranulum genera prevail are associated with a lower risk of asthma attack than microbiotas dominated by more pathogenic bacteria, particularly the Staphylococcus, Streptococcus and Moraxella genera. Furthermore, a shift to Moraxella at the onset of an attack (peak expiratory flow in the yellow zone) is associated with a higher risk of exacerbation. These results are consistent with those of previous studies showing that colonization of the upper airway by opportunistic pathogens, particularly Streptococcus, Moraxella and Haemophilus, is more common in asthmatics than in healthy subjects.

Protective bacteria

In addition, at the onset of an asthma attack, the relative abundance of Corynebacterium was inversely associated with the likelihood of severe exacerbation. It should be noted that Corynebacterium (the most abundant genus identified in nasal microbiota) less frequently prevails in the nasal microbiota of asthmatic adults, suggesting a protective effect, perhaps through competitive colonization. Corynebacterium and Dolosigranulum may indeed inhibit the growth of Streptococcus by releasing antibacterial substances.

Cause or consequence?

Therefore, the microbiota of the upper respiratory tract is linked to events that take place in the lower respiratory tract. However, the design of the study prevents from drawing any conclusion on causality relationship. It is not yet known whether changes in the microbiota I) give rise to asthmatic activity, II) are the consequence or cause of a viral infection, or III) are the result of a two-way dialogue between the microbiota and the immune response of the host at a mucosal level during attacks and exacerbation. Changes in the microbiota may also be due to poorer asthma control or an inflammation of the respiratory tract.

Atopic dermatitis (atopic eczema) is a chronic inflammatory skin condition, characterized by topical dryness, red lesions and outbreaks of itching. These changes to the skin barrier may be influenced by genetic and environmental factors, with possible implications for the skin microbiota. Previous studies have shown that the skin microbiota of subjects with atopic dermatitis is different from that of healthy skin. In particular, Staphylococcus aureus may colonize the damaged skin of patients and possibly contribute to worsen eczema flare-ups.

The effect of laser light on skin flora

One of the treatments for this type of dermatosis is laser light, especially 308 nm excimer laser. Although the efficacy of this laser light has been demonstrated, a question remains: does it affect the composition of the skin microbiota and its role in atopic dermatitis? A Japanese team is looking into this question by evaluating the development of microbial flora, lesions and skin barrier function of 11 patients following two months of weekly laser treatment.

Targeting Staphylococcus aureus

The primary post-treatment observation was reduced lesion severity, higher hydration index and improved skin barrier function. With respect to the skin microbiota, the researchers observed an increase of certain bacteria indicating improvement of skin hydration and, in particular, decreased abundance of harmful species of bacteria, i.e. Staphylococcus aureus. The laser treatment may therefore have a positive effect on the microbiota, especially by reducing the content of Staphylococcus aureus, which could result in an improvement of skin lesions in patients with atopic dermatitis.

More effective and less toxic than chemotherapy, CAR-T cell immunotherapy is the subject of an increasing number of clinical trials. This treatment genetically modifies T cells to give them a Chimeric Antigen Receptor (CAR) which allows them to specifically recognize and kill tumor cells. Despite impressive results in some patients, the clinical response to CAR T cells remains highly variable.

The authors’ hypothesis

In this review, the authors suggest that manipulating the gut microbiota could improve responses to CAR-T cells, even though there are currently no published results confirming this. The only study available, a single-center observational study involving 25 patients receiving CAR-T cells, shows that responders have a different microbial make up than non-responders, suggesting a possible link between intestinal microbiota and CAR-T cell response. Nevertheless, the authors base their hypothesis on a number of points: the growing nonclinical and clinical evidence throwing light on the escape mechanisms in CAR-T cell non-responders; clinical evidence of improvement in responses to immune checkpoint inhibitor (ICI (sidenote: Immune checkpoints are used by tumors to protect themselves from immune system attacks and may be blocked by ICI therapy in order to restore the immune system function. ) *) therapy via manipulation of the gut microbiota (diversity and composition); and finally, the common immunological characteristics of CAR-T cells and ICI.

What are the practical recommendations?

If the microbiota is involved in responses to CAR-T cell therapy, the use of broad-spectrum antibiotics during immunotherapy may result in dysbiosis, reduced response to treatment and a reduced survival rate. As regards probiotics, although certain bacterial groups may have a positive effect on responses to immunotherapy, the results of clinical studies are not always consistent enough to clearly separate taxa into “favorable” and “unfavorable” categories. Consequently, a scientifically prepared “cocktail” of live bacteria remains out of reach. In the meantime, the team recommends not using commercially available probiotics during cancer treatment, since they may dilute the native intestinal flora and potentially make it less diverse. Similarly, the team advises against the imprudent use of broad-spectrum antibiotics during immunotherapy and CAR-T cell therapy.

The microbiotas of human epithelia are subject to mucosal immune defense mechanisms and their microbial composition changes significantly in early life during development of the immune system. Their lack of maturation is associated with certain diseases, although the development mechanisms for a healthy microbiota remain poorly understood. The nasal system remains one of the least studied of the various epithelial sites, even though the nostrils can harbor pathogenic agents responsible for serious systemic respiratory infections, such as Staphylococcus aureus or Moraxella catarrhalis. This explains the importance of this study of the nasal microbiota in 467 healthy volunteers across 3 different age groups: 155 children (average age of 5 years), 171 young adults (average age of 19 years) and 141 elderly subjects (average age of 82 years) respectively chosen to represent age groups in which immune status is not yet developed, is mature or is declining.

A characteristic microbiota for each age group

Analysis of the six dominant microbial phyla found that the composition of human nasal microbiota changed significantly with age and that microbial diversity decreased on reaching adulthood. Although Moraxella was predominant in children, this species was almost absent in the other two age groups. The abundance of Staphylococcus was multiplied by a factor of 4.4 during transition to adulthood, to the extent of becoming the predominant species in young adults. The opportunistic pathogen Dolosigranulum pigrum, which can cause upper respiratory tract infections, nosocomial pneumonia and septicemia, decreased by a factor of 2.4 between childhood and early adulthood. Finally, in elderly subjects, the increase of Staphylococcus and decrease of Dolosigranulum observed in young adults were partially reversed.

The protective effect of S. epidermidis

Based on their results, the researchers also proposed a potential mechanism though which one specific species–Staphylococcus epidermidis–, working in tandem with the host’s immune system, could lead to the exclusion of nasal pathogens. S. epidermidis could stimulate the production by nasal keratinocytes of antimicrobial peptides which kill pathogenic bacteria while S. epidermidis is resistant to these peptides due to its biofilm. This mechanism of symbiotic interaction between a bacterium from the human nasal microbiota and the innate host defense could in this way contribute to the exclusion of pathogenic agents, stabilization of the microbiota, and could help the host’s immune system differentiate between pathogenic and commensal bacteria.

The role of the gut microbiota has been demonstrated in many disorders (obesity, diabetes, etc.): metabolites and other microbial signals could affect the amount of circulating lipids, including triglycerides and HDL. Several studies have also established a link between gut microbiota and several amino acids implicated in diabetes and cardiovascular diseases. Building on progress in the field of metabolomics, a team has evaluated the relationship between gut microbiota and circulating metabolites. This was done via characterization of the metabolome (all metabolites) from 2,309 individuals from 2 prospective cohort studies (Rotterdam and LifeLines-DEEP). It emerged from this that a total of 32 bacterial groups were associated with certain circulating metabolites after adjusting for age, sex, body mass index (BMI) and medication (including lipid-lowering agents, proton pump inhibitors and metformin).

Microbiota and lipoproteins

Among the 32 microbial taxa identified, 18 were associated with VLDL particles (associated in turn with metabolic and cardiac diseases, and type 2 diabetes), and 22 others with HDL particles (well known for their protective role), with, however, differences depending on the size of the HDL particles, suggesting that this class of lipoproteins is heterogeneous with respect to its metabolic functions and effects (protective or harmful). 13 microbial taxa–of which some are well known for their association with BMI (Christensenellaceae), others for their association with bile acid metabolism (Clostridiaceae 1), etc.–were associated with both VLDL and HDL particles. However, the unclear association between gut microbiota and LDL and IDL (sidenote: Intermediate Density Lipoprotein ) * particles suggests there are different relationships depending on the class of lipoproteins. Finally, 15 bacterial groups, including the Ruminococcus gnavus group (sign of a less diverse gut microbiota and more present in patients with atherosclerosis), were associated with serum triglycerides.

Ketone bodies, amino acids, etc.

Associations were also reported between gut microbiota and:

• ketone bodies, notably acetates of short-chain fatty acids (SCFAs) produced by colonic bacteria which could promote metabolic syndrome.

• amino acids including isoleucine, associated with diabetes mellitus and cardiovascular diseases.

• acute phase inflammatory markers, notably glycoproteins implicated in inflammatory diseases and cancer, and associated with cardiovascular diseases.

According to the authors, the potential mechanisms by which gut microbiota could affect the amount of circulating lipids could implicate bile acids and SCFAs. If so, the gut microbiota could become a potential target for curative and preventive interventions.

Healthy microbiota in a healthy body: this might be the conclusion of a Chinese study aimed at finding the link between the level of sporting activity and the composition of the gut flora. The study stems from the recent scientific discovery that physical activity influences the diversity and abundance of the gut microbiota. However, it remained unclear whether there was a link between the level of sporting activity and the “quality” of the microbes in the gut, so the researchers studied the gut bacteria populations of 28 practitioners of wushu (traditional Chinese kung fu): 12 elite athletes and 16 lower-ranking athletes, all selected from the same professional team at Beijing Sport University to limit the impact of diet variations on the results. The only difference between them was the significantly higher number of training hours per week for the elite athletes.

Benefits of martial arts

The study concluded that the higher the level of the professional martial artist, the more diversified and abundant the beneficial bacteria in their gut microbiota. The bacterial groups found specifically in high-level athletes and the molecules they produce (short-chain fatty acids) make an important contribution to the metabolism of carbohydrates and amino acids, improving muscle performance. Conversely, lower-level athletes had a higher ratio of “harmful” bacteria, which are implicated in certain chronic inflammatory diseases and other illnesses.

Training-friendly bacteria

Another reason for exercise fanatics to be pleased is the existence of a direct link between the abundance of certain bacteria and the amount of high-level physical training undertaken, further proof, if any were needed, that to train (hard) is never in vain. However, the dynamics involved must be studied more carefully before any conclusion is reached on changes to the gut flora due to training, nutrition or probiotics aimed at improving the performance of ordinary athletes.

Infertility affects between 10% and 15% of couples, with gender equality called for in this domain, since men are the origin of the problem in half of cases. Among the environmental factors to blame is obesity, which leads to a reduction in sperm quality. However, the excessively rich diet which causes obesity is also associated with a change in the composition of the gut microbiota (dysbiosis (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.   ) ). Might the ecosystem in our gut be a key factor in male infertility linked to junk food?

Fewer and less mobile sperm

This is the hypothesis put forward by Chinese researchers. To assess its validity, they put together four groups of mice: one group received a balanced diet and another a high-fat diet. Both served as donors in a fecal microbiota transplant to two other groups of mice subsequently fed normally. Unsurprisingly, the junk food diet resulted in weight gain, but it was also accompanied by dysbiosis and by endotoxemia, a bacterial infection which causes a chronic local inflammation known to impair spermatogenesis. Analyses on the mice’s semen showed a significant decrease in sperm count and sperm motility. Comparable results were observed for mice fed normally but receiving a fecal transplant from fattened members of the same species, though without any weight gain or metabolic changes. Dysbiosis and endotoxemia are thought to cause inflammation of the intestines and scrotum, resulting in impaired sperm production and maturation. The link between dysbiosis, endotoxemia and lower sperm quality has also been confirmed in infertile men.

Treat dysbiosis to restore fertility?

The authors therefore suggest that restoring gut microbiota may be a new approach to treating male fertility problems, particularly for men with metabolic syndrome.

Crohn's disease (CD), an inflammatory condition that can affect any part of the digestive tract, is becoming increasingly common among children. Like all forms of inflammatory bowel disease (IBD), it appears to be closely related to disruptions in the gut microbiota. In order to gain an overview of its structure in the early stage of the disease, a team studied the microbiota in stool samples from 64 untreated children and 18 healthy control subjects.

Reduced diversity

The abundance (number of taxa) and diversity (relative abundance) of microbiota in young patients with CD was lower than in control subjects: 11 genera and 17 species differed significantly between the two groups, with fewer Actinobacteria and Firmicutes and a greater abundance of Enterococcus in the CD group. The authors also report a significant reduction in the abundance of some butyrate-producing genera and species such as Bifidobacterium adolescentis. These results are consistent with those of previous studies carried out on children and adults.

Local inflammation

Furthermore, a decreased abundance of several taxa and lower microbiota diversity are observed when fecal calprotectin levels (an inflammation marker) and disease activity increase, suggesting a link between dysbiosis and inflammation of the gastrointestinal tract. While it remains unclear whether the dysbiosis causes the inflammation or is a consequence of it, the authors suggest a vicious circle, with persistent inflammation reinforcing dysbiosis and vice versa. On the other hand, no change in microbiota diversity is associated with biochemical markers such as the C-reactive protein (CRP), suggesting that local inflammation in the gastrointestinal tract reflected by a high level of calprotectin is more important than the general state of inflammation.

Towards treatments targeting the microbiota?

According to the authors, if a dysbiosis of the intestinal microbiota is one of the risk factors for the development and/or persistence of inflammation in IBD, then treatment targeting microbiota (antibiotics, pro- and prebiotics, fecal microbiota transplant) should be a therapeutic goal. In addition, the advantages of a prophylactic treatment based on microbiota for high-risk groups are clear. Lastly, the absence of Fecalibacterium prausnitzii and B. adolescentis (or even the lower abundance of Roseburia) in the stool may serve as a biomarker of the dysbiosis which signals CD.