HOST-RELATED EFFECTS

The composition of the skin microbiota is strongly influenced by the host, specifically by their age, sex, genes, immune status, concomitant health conditions (dermatological or otherwise), the skin area in question, interactions between microorganisms, diet and stress levels.²

The initial colonization of a newborn baby’s skin depends on the mode of delivery^4,7: children born vaginally acquire vaginal bacteria (Lactobacillus, C. albicans), while those born by caesarean section acquire skin microbes (Staphylococcus, Streptococcus). Within a few hours of birth, sebum secretion increases sharply. This continues for several days before decreasing.² The immature immune system facilitates colonization due to the lack of any inflammatory response.⁴

At puberty, the skin microbiota undergoes a profound restructuring due to hormonal changes that stimulate sebaceous secretions. It contains more lipophilic organisms (Cutibacterium, Malassezia), whereas previously it had been dominated by Firmicutes, Bacteroidetes and Proteobacteria, with a diverse fungal community.⁴

ENVIRONMENTAL EFFECTS

Many external factors also influence the composition of the skin microbiota², including lifestyle, domestic and personal hygiene, cohabitation, geographical location, sunlight, occupation (and work clothing), etc. For example, contact with other humans, but also with pets and objects (telephone, computer keyboard, classroom objects, etc.), modifies the skin microbiota and explains the similarities observed between the microbiota of members of the same household or group.³

Moreover, the conditions in a given environment affect the different areas of the skin to different degrees. For example, some skin areas (e.g. hand) have more physical contact, others are less exposed to ultraviolet light, etc.^3,4 Despite this, the skin microbiota remains relatively stable in adulthood, suggesting reciprocal beneficial interactions between microorganisms and host.⁶

BACTERIA, FUNGI, VIRUSES AND PARASITES

Although easily accessible, the skin microbiota remains poorly understood. Its density is believed to be low compared to that of the large intestine, instead resembling that of the small intestine, i.e. around 10¹¹ bacteria.¹ It is the fourth largest microbial niche in the body in terms of the number of microorganisms, just after the digestive tract, the oral cavity and the vagina.²

It hosts several bacterial phyla (Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes), archaea, and fungal species mainly from the genus Malassezia.^2,3 Among the bacterial species identified are included Cutibacterium acnes and Staphylococcus epidermidis, although the strains present differ depending on the individual, the state of their skin (healthy or otherwise) and the sampling site.^3,6

Lastly, although not well described,² numerous viruses (papillomavirus, adenovirus, etc.) have been identified on the skin of healthy individuals, as well as phages that target C. acnes and S. epidermidis, suggesting the existence of a complex virome. Parasites (such as Demodex mites, etc.), few in number, are even more scantly described.³

Three major niches are generally identified based on properties such as pH, temperature, humidity, perspiration levels and lipid content:^1,3,4

• sebaceous areas (face, chest, back) that secrete lipid-rich sebum;
• dry areas (forearms, palm of the hand);
• humid areas (armpits, elbow crease, nostril, back of the knee and groin), where numerous sweat glands participate in thermoregulation (sweat), acidify the skin and secrete antibacterial peptides.

Some authors distinguish a fourth area in the foot (nails, heel and space between toes)⁴ (see table).

These areas are separate ecological niches, each with a unique microbial community: the most exposed and dry areas, such as the hands, are the most diverse; the armpit, which is moist and rich in sweat, is dominated by Corynebacterium and Staphylococcus species; while lipid-rich areas, such as the face, display much less diversity (Cutibacterium bacteria, fungi of the genus Malassezia, and Demodex folliculorum mites).³

Microbiota also vary in density from one skin area to another: from 10² bacteria per cm² on the fingertips or back, to 10⁶ bacteria per cm² on the forehead or in the armpits.²

On the skin’s surface, the deeper into the stratum corneum the fewer microorganisms are present.¹

Then, from the surface to the subcutaneous regions, the microbiota changes and gradually loses its individual characteristics.^4,5

In the dermis and subcutaneous adipose tissues, there seems to be more Proteobacteria while there are less Actinobacteria and Firmicutes than in the epidermis.²

Bacterial vaginosis is a quite common disorder in women of reproductive age, with a prevalence estimated at 10%–30% worldwide. It is associated with an increased risk of infertility and complications during pregnancy. It is also a risk factor for contracting sexually transmitted diseases. The condition is characterized by an imbalance of the vaginal microbiota and a biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria. This biofilm is frequently refractory to antibiotic treatment. Antibiotics are effective in quickly reducing symptoms but are associated with a recurrence rate of up to 60% within six months of treatment. A new study has investigated endolysins (sidenote: Endolysins Bacteriophage enzymes that lyse the bacterial wall, allowing the release of phages. )  of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages (sidenote: Prophages Bacteriophage genomes integrated into the host genome. (Saussereau and Debarbieux 2012) )  as an alternative treatment.

Bactericidal effect 10 times higher than wild type

To this end, the authors generated several engineered endolysins via domain shuffling. They compared their bactericidal activity on Gardnerella strains to that of wild-type endolysins. The bactericidal activity of the recombinant endolysins was 10 times that of any wild-type enzyme. When tested against a panel of 20 Gardnerella strains (from 4 species (sidenote: G. vaginalis, G. leopoldii, G. piotii and G. swidsinskii ) ), the most active endolysin, called PM-477, showed superior efficacy compared to the antibiotics tested (metronidazole, tinidazole, clindamycin). Furthermore, PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. According to the authors, PM-477 is highly selective for Gardnerella and kills strains of each of the four main species without affecting beneficial lactobacilli or other species typical of the vaginal microbiota. The effect of PM-477 was confirmed by microscopy in mixed cultures of Gardnerella and lactobacilli. PM-477 (at 460 µg/mL for 5 h) lysed G. vaginalis and G. swidsinskii cells in monoculture, but also selectively lysed them in mixed cultures alongside lactobacilli without affecting the latter.

Efficacy in patient samples

To go further and analyze the efficacy of PM-477 in a physiological environment closely resembling the in vivo situation, the researchers treated vaginal swabs from 15 bacterial vaginosis patients and analyzed them by fluorescence in situ hybridization (FISH). They showed that in 13 of the 15 cases, PM-477 eradicated the Gardnerella bacterium and physically dissolved the biofilms without affecting the vaginal microbiota. For the authors, endolysins are a promising therapeutic alternative to antibiotics for the treatment of bacterial vaginosis. This is a significant finding since antibiotics are frequently a cause of recurrence and resistance in the treatment of the disease.

What causes Autism Spectrum Disorders (ASD)? The question has puzzled the scientific community for decades. While the gut cannot fully explain the causes of ASD (characterized by difficulties in socializing and communicating, or even obsessive-compulsive disorders (OCD)), it may provide some of the answers. These answers are to be found in the billions of bacteria and other microorganisms that populate the gut microbiota, for better or worse.

Gut disorders and ASD: a dangerous liaison

Since ASD was first described in 1943, numerous symptoms have been identified. Gut disorders (diarrhea, constipation, irritable bowel, etc.) are among the most standard physical symptoms. Children with ASD experience three to four times more gastrointestinal disturbances than the norm. Severe autism often goes hand in hand with the most severe gut disorders–and vice versa. In fact, researchers have even shown that autistic patients show an improvement in behavior following treatment of a gastrointestinal disorder. They therefore became interested in the mechanisms behind these gastrointestinal disorders and took a closer look at the gut microbiota.

A microbiota that believes itself to be the brain

Observation no. 1: autistic patients often present an altered gut flora (dysbiosis) that is poor in beneficial bacteria and richer in microbes involved in certain gut disorders (diarrhea, constipation, etc.). Not content with troubling the gut, these microbes also produce “signal” molecules used by the gut and the brain to communicate. Produced to excess, these molecules could interfere with the communication process and lead to behavioral disorders such as those encountered in ASD.

A leaky gut?

Observation no. 2: the gut barrier no longer does its job, i.e., preventing microbes, allergens and other foreign molecules from entering the bloodstream. The immune system is activated as a result, triggering inflammatory reactions. Many autistic patients exhibit gut permeability, gut and neuronal inflammation and gut disorders associated with a response to heightened stress. These data suggest a strong gut-brain link in ASD. However, the mechanisms by which gastrointestinal disorders contribute to autism are extremely complex. Further research is therefore required to identify therapies to treat these gut problems and improve the quality of life of patients with ASD.

Lung cancer is the leading cause of death by cancer worldwide. While active tobacco use is the main risk factor, 25% of cases occur in non-smokers, a high percentage not fully explained by the major risks identified (passive smoking, pollution, family history, etc.). In addition to the gut microbiota, which is involved in the development of certain gastrointestinal cancers, other microbial ecosystems have also been associated with cancer risk. In this study, the authors investigated whether the oral microbiota’s composition and its ability to colonize the respiratory tract are involved in the development of lung cancer.

Depleted microbiota, increased risk

Their prospective study involved the long-term follow-up of more than 136,000 never-smoker Shanghai residents (61,500 men, 75,000 women), with follow-up visits every 2-3 years. A saliva sample taken at the outset was analyzed in all subjects reporting lung cancer and in an identical number of controls, matched for sex, age, date and time of sample collection, previous antibiotic treatment, etc. Metagenomic shotgun sequencing was then used to compare the 114 subjects diagnosed with lung cancer with the same number of controls. This analysis found a greater risk of developing lung cancer where the oral microbiota lacks bacterial diversity.

Greater abundance of Firmicutes is harmful

The inherent composition of the oral microbiome also appears to play a major role. Among the population studied, an increase in the relative abundance of Spirochaetes and/or Bacteroidetes was associated with a lower risk of lung cancer. Conversely, a greater abundance of bacteria belonging to the Firmicutes phylum, particularly Lactobacillales, was associated with an increased risk of lung cancer. The authors point out that these results coincide with those of previous studies showing a link between Firmicutes and certain respiratory diseases (chronic obstructive pulmonary disease or COPD, squamous cell carcinoma of the head and neck, and lung cancer).

ENT microbiota: further research required to clarify its field of action

This large-scale characterization of the oral microbiota sheds new light on the causes of lung cancer in non-smokers. The geographical homogeneity of the study reinforces the relevance of its findings but limits their scope. Further work on different populations and in different locations would help clarify the role of the ENT microbiota in the development of lung cancer and other respiratory diseases.

Crohn’s disease and ulcerative colitis are both forms of IBD and have one thing in common: they cause uncontrolled inflammation of the lining of a section of the digestive tract, resulting in various symptoms during inflammatory flares. While there is currently no cure for these diseases, there are treatments such infliximab (sidenote: Infliximab A biotherapy that neutralizes TNF-α, the protein responsible for tissue inflammation. ) (IFX) aiming at reducing inflammation. However, a third of patients do not respond to this therapy and there is currently no biomarker (sidenote: Biomarker An objectively measured biological characteristic that makes it possible to evaluate responses to treatment. This response can be complete or partial. )  that predicts response to treatment. The researchers in this study may have found the answer in the gut microbiota.

Gut microbiota differs before treatment...

Numerous studies have shown a link between the composition of the gut microbiota (bacteria and, more recently, fungi) and IBD. Therefore, in order to identify markers that predict response to IFX therapy, the researchers evaluated the impact of IFX treatment on the gut microbiota composition of 72 IBD patients (sidenote: 25 patients with Crohn’s disease (CD) and 47 with ulcerative colitis (UC). ) . Bacterial and fungal diversity in the gut microbiota was analyzed using fecal samples collected before treatment and 1 year after beginning of therapy. The patients were classified into three groups according to their response to treatment. The study revealed that the bacterial and fungal profiles of the three groups differed significantly before start of therapy.

...offering a predictive tool

Significant differences between the three groups of patients were also observed after initiation of treatment: non-responders had lower contents of anti-inflammatory bacteria and higher contents of pro-inflammatory bacteria and fungi (such as the genus Candida) compared with responders. These results suggest that the gut microbiota is involved in responses to treatment.

Based on these findings, the researchers subsequently identified certain bacteria and fungi present in the gut before start of treatment which could be used to predict responses to IFX therapy. Early identification of non-responders would permit rapid modification of treatment, limiting side effects and reducing the costs involved. A fully positive approach!

Theobroma cacao is the botanical name for the cacao tree; but did you know that Theobroma means “food of the gods” in Greek? Once reserved for priests and kings, chocolate has, fortunately, become more democratic. Today, it is consumed and appreciated throughout the world for its delicious taste and health benefits. With a cocoa content of more than 80%, dark chocolate is undoubtedly the most beneficial to health. For example, it contains specific compounds that could alleviate complications in chronic kidney disease (CKD).

Dark chocolate and gut microbiota: a winning combination?

The kidneys of patients with CKD have reduced functional capacity and no longer filter blood properly. This failure leads to an accumulation of molecules such as uremic toxins (sidenote: In total, more than 80 molecules are considered uremic toxins, among them hormones, peptides and even organic compounds. )  in the blood. These patients have an unbalanced gut microbiota (dysbiosis) that may contribute to the production of these toxins. Eating cocoa may modulate the gut microbiota by promoting the colonization by bacteria with known beneficial effects (Lactobacillus and Bifidobacterium) in the gut. A number of studies have also shown that, by modulating the gut microbiota, the ingestion of chocolate improves the integrity of the gut barrier, decreases inflammation and reduces uremic toxins.

Dark chocolate, the white knight of your cardiovascular system

Patients with CKD have a high risk of cardiovascular disease and premature death. Several studies have shown that the regular consumption of dark chocolate has a cardioprotective effect in healthy individuals. How so? By improving blood circulation, specifically, improving functioning of the blood vessels and reducing blood pressure. This improvement also leads to a reduced risk of stroke.

Munch on chocolate to boost your mood

We tend to forget that chronic illness often has a psychological impact on the patient. Beyond the simple pleasure of taste, the regular consumption of dark chocolate also stimulates the production of serotonin (a neurotransmitter involved in the regulation of behavior), which has an antidepressant effect. Although the consumption of dark chocolate (cocoa content of more than 80%) seems an interesting therapeutic alternative for patients with CKD, its potential impact on inflammation, cardiovascular risk and the gut microbiota has not yet been studied in a prospective clinical trial. But don’t let that stop you from treating yourself to a square of chocolate!

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Newborns subjected to antibiotic therapy reportedly exhibit an altered gut microbiota composition. However, the clinical or microbiological long-term consequences of this exposure remain unknown. Given the causal links between the intestinal microbiota and growth, obesity, and metabolic disease, researchers have suggested that neonatal antibiotic exposure might exert a long-lasting effect on childhood growth by disrupting the natural gut microbiota colonization process.

Altered development...

A study on 12,422 children born from singleton pregnancies at full term provided a host of information. The infants studied had no known growth abnormalities and did not require long-term prophylactic antibiotic treatment. 9.3% of the neonates in the study were exposed to antibiotics (sidenote: Combination of intravenous benzylpenicillin and gentamicin for most infants )  within the first 14 days of life. Among exposed newborns, only boys had significantly lower weights compared to non-exposed children throughout the first six years of life. They also exhibited a significantly lower height and body mass index (BMI) between the ages of 2 and 6 years. This result was confirmed in a German cohort of 1,707 children followed from birth to 5 years. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with a significantly higher BMI in both boys and girls.

...and a modified gut microbiota

To study the effect of neonatal antibiotic exposure on the gut microbiota, fecal samples were collected at the ages of 1, 6, 12, and 24 months from a separate group of 33 newborns, 13 of whom received intravenous benzylpenicillin and gentamicin within the first 48 hours of life. Twenty healthy newborns not exposed to antibiotics in the neonatal period were chosen as controls. The fecal microbiota was analyzed via 16S rRNA gene sequencing. Significant differences between the gut microbiota composition of the antibiotic-treated and control groups were observed after 1 and 6 months, demonstrating the persistence of the effect of antibiotic exposure on the microbiota. The genus Bifidobacterium was most substantially affected, with its content significantly reduced up to 24 months after antibiotic exposure.

Gut dysbiosis in question?

To establish whether causal relationships exist between neonatal antibiotic exposure, gut dysbiosis and child growth, the researchers conducted a complementary study in germ-free mice (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. ) . The mice received a fecal microbiota transplant (FMT) with feces obtained from antibiotic-exposed children 1 month and 2 years after the antibiotic treatment. A significant reduction in weight gain was observed in male mice that received FMT from antibiotic-exposed infants, as compared to male mice that received FMT from non-exposed infants. In contrast, growth in female mice was not affected.

These findings suggest a causal link between exposure to antibiotics during the first six years of life and growth disorders during childhood which could be caused by the gut dysbiosis that appears during the development of the gut microbiota.