A growing body of research is pointing to the existence of distinct microbiotic signatures for different food allergies. This field of research is helping to position the microbiota as a central player in the development of such allergies. A new longitudinal study published recently in the Journal of Allergy & Clinical Immunology has shed new light on possible links between the onset of a peanut allergy and microbiota.
 
As this allergy generally develops during infancy, the researchers studied the microbiota of children at risk of developing a peanut allergy at the age of 10 months (SD: 3.1), then at 9 years (SD: 0.6). Within this population, 35 (28.7%) of the children developed a peanut allergy before the age of 9.

A different gut microbiota signature from the very first months of life

These 35 children in the PA (Peanut Allergy) group had a less diverse microbiota at inclusion (p=0.014) than the NPA (Non-Peanut Allergy) group. Their microbiota diversified with age, while that of the NPA group remained stable.

At age 9, both groups showed a comparable microbiotic diversity.

At inclusion, the PA group had a higher proportion of Clostridium sensu stricto 1 sp, while Streptococcus sp was more prevalent in the NPA group. By the age of 9, the relative abundance of these two species was normal in both populations. Conversely, the abundance of the Bifidobacterium sp species dropped in the PA group and even became higher in the NPA population.

Allergy development is identified as being associated with altered levels of 139 metabolites in the metabolome (FDR ≤ 0.05). 

These metabolites are associated with a histidine metabolism pathway (FDR = 0.037, pathway impact = 0.28).
Six short-chain fatty acids were studied in particular. The butyrate and isovalerate levels dropped in the PA group, while the isovalerate level remained stable in the NPA group with an increase in butyrate.

Is there a pathophysiological mechanism of peanut allergy?

The authors speculate that the lower microbiota diversity in PA infants may suggest that they have less stable gut communities during this phase of rapid immune system development.

The reduced relative abundance of Bifidobacterium sp, known for its use as an anti-allergy probiotic and for inducing mast cell apoptosis in mice, could also play a role in the development of allergies. 

The authors also note that the micro-organisms present in the gut of children predisposed to developing this allergy species capable of producing metabolites originating from the histidine metabolism pathway, the precursor of histamine, the effector characteristic of allergic reactions.

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Travel is a great way to make memories...including some you'd rather not have! While it's no surprise that a third of the 267 Americans studied who traveled abroad reported diarrhea, it's more worrying that 61% of travelers left some of their protective gut microbial diversity behind. Worse still, many returned with intestinal stowaways (Escherichia and other enterobacteria such as Klebsiella, Enterobacter and Salmonella) and sacrificed their intestinal population of Alistipes on the altar of exoticism.

Bacteria and antibiotic resistance

Some would say it's just a few bacteria! Yes, but many of which are resistant to antibiotics. And therein lies the problem. On their return from abroad, 38% of the 267 travelers had acquired at least one of the 3 antimicrobial (sidenote: Antimicrobials Antimicrobials — such as antibiotics, antivirals, antifungals and antiparasitics — are drugs used to prevent and treat infections in humans, animals and plants. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance  ) -resistant organisms targeted by this study, and above all, 98% of them had acquired vicious enterobacteria (generally E. coli), capable of resisting the effects of many antibiotics and currently representing enemy No. 1 in the fight against antibiotic resistance.

In all, the group of 267 American travelers in this study returned from their 2-week peregrinations abroad with 72 new resistance genes, including 15 of public health concern!

Travel advice

If we don’t want to abandon all thought of travel, what can we do to reduce the risk of importing antibiotic resistance?

Known to be effective in the prevention of traveler's diarrhea ^2,3, probiotics would not have any added value here to prevent bringing home these multi-resistant germs, according to the authors. The study suggests that the composition of one’s microbiota prior to departure has no impact on the acquisition of these resistant bacteria. There's no need to deprive yourself of street food once you're there—it doesn't change anything.

On the other hand, eating raw vegetables seems very risky! Don't let your guard down when visiting family or friends abroad; eat only well-cooked vegetables, peel your fruit and, as at home, wash your hands regularly!

And be particularly vigilant when traveling to South Asia, a destination that goes hand in hand with an increased risk of returning with an intestinal stowaway!

For children, peanut allergy is a common but serious challenge. In Western countries, it affects almost 2% of children. ¹ Symptoms include breathing difficulties, swelling of the throat, diarrhea, nausea, skin rashes, and fainting. These symptoms vary in severity, but the most serious, anaphylaxis – an intense whole-body reaction – can prove fatal. ^2,3 Peanut allergy often manifests itself in early childhood, can be much more severe than other food allergies, and, unlike them, lasts into adulthood in 80% of cases. ¹

A link between the microbiota and food allergy?

What about the gut microbiota? For many years, it has been known that the microbial communities in the gut also play a key role in building the immune system. Recent research even suggests that the gut microbiota may be involved in the development of food allergies. Patients with food allergies present an unbalanced gut microbiota.

So, what happens in early childhood before allergies even appear? Researchers in the US set out to answer this question by analyzing the microbiota of 122 children from infancy to the onset of the allergy. Their aim was to better understand how the allergy develops, with the hope of one day being able to prevent it.

Tell me about your microbiota, and I’ll tell you your future allergy...

The researchers’ first finding was that patients who developed peanut allergy around the age of nine had a poorly diversified gut microbiota during their first months of life. Their microbial communities evolved more dynamically, with a less homogeneous distribution of species compared to the microbiota of children who did not develop the allergy, while their gut flora evolved more continuously and homogeneously over time.

Their second finding was that certain species of the Clostridium genus were more present in infants who did not have peanut allergy, while Streptococcus sp were more present in those who did. By the age of nine, Bifidobacterium, well-known beneficial bacteria, were more present in non-allergic patients.

In addition to the changes in abundance of certain bacteria being different between the two groups of children, the authors observed that the metabolites produced by the microbiota, i.e., the metabolome, were different in the children who developed an allergy. In particular, certain  SCFAs (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. 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. ) , such as butyrate and isovalerate, decreased over time in the children who subsequently developed an allergy. Isovalerate is already known for its protective properties against allergy (asthma and atopy).

The development of peanut allergy was associated with changes in 139 metabolites, and particularly with a pathway for the metabolism of histidine, the precursor of histamine, a bioactive molecule released during allergic reactions.

Respiratory, gastrointestinal and neurodevelopmental complications: preterm birth (sidenote: Preterm birth birth before 37 completed weeks of gestation. There are sub-categories of preterm birth, based on gestational age:
- extremely preterm (less than 28 weeks);
- very preterm (between 28 and 32 weeks);
- moderate to late preterm (between 32 and 37 weeks). Source: WHO ) is the main cause of neonatal morbidity and mortality. The vaginal microbiota seems to be involved, but the underlying mechanisms remain poorly understood. This flora can change rapidly during gestation, due to hormonal changes, genital infections, antibiotics, etc. A team of researchers and clinicians from the states of New York and Virginia tracked the genome of the vaginal microbiota of 175 American women throughout their pregnancies (40 of whom subsequently experienced spontaneous preterm delivery, and 135 of whom delivered at full term).

Higher genetic diversity

The study shows that the two types of pregnancy differ in terms of vaginal microbiota composition: certain bacterial species of the Lactobacillus genus, such as L. helveticus, L. crispatus, L. gasseri and L. jensenii, are associated with full-term pregnancies, while Megasphaera genomosp, Gardnerella spp. and Atopobium vaginae are linked to preterm births.
Another finding is that the genetic diversity of the vaginal microbiota is higher in the first half of pregnancies that end preterm, due to Gardnerella species. More precisely, the nucleotide diversity (sidenote: Nucleotide diversity number of nucleotide differences for a given sequence for 2 individuals (here 2 bacteria) randomly selected in the population. ) of Gardnerella spp. increases at the start of pregnancies that end preterm - peaking at around 13 weeks of gestation, then returning to its initial value at around 20 weeks of gestation - whereas it remains stable in pregnancies that are carried to term. The genetic diversity of Gardnerella spp. during the first half of pregnancy therefore appears to affect pregnancy outcomes and could perhaps be used as a biomarker for the early diagnosis of preterm birth.

An adaptive evolution of Gardnerella

But how can we explain this peak in Gardnerella nucleotide diversity? Compared to other bacteria, Gardnerella shows a 1.5-fold higher growth rate at the start of pregnancy, more frequent genetic recombination (sidenote: Genetic recombination exchange of genetic information (DNA or RNA fragments in the case of certain viruses) to create new genetic combinations and thus new genomes, ensuring genetic admixture and the maintenance of a diversity that enables adaptation to any change in the environment. ) and greater selection of mutations that benefit this bacterium (and increased elimination of deleterious mutations).
Antibiotics and other xenobiotics are thought to be involved. In fact, the more diversified gene pool of G. swidsinskii seems to correspond to an adaptation to drugs, confirming a previously suggested effect of xenobiotics in the vaginal environment; and vaginal microbiota associated with preterm birth exhibit higher antibiotic resistance potential (sidenote: increased presence of phage-borne antibiotic resistance genes. ) .

From vaginal microbiota to the host

Genomic variation in vaginal bacteria is therefore believed to affect the host’s phenotypes (including pregnancy outcomes). However, the authors do not rule out another explanation, even if they consider it unlikely: the associations between microbial genetic diversity and pregnancy outcomes could also result from unmeasured confounding factors (drugs, chemical compounds, etc.) that might act on both variables.

According to the International Microbiota Observatory, more than 9 out of 10 (95%) people who repeatedly benefited from information from their healthcare professional had adopted specific behaviors to maintain a balanced microbiota. What about antibiotics? Well, according to the same study, only 1 in 3 patients said their healthcare professional had informed them that taking antibiotics could upset their microbiota balance. Because information provided by healthcare professionals is a game-changing vector of behavior, during the WAAW 2024 (18-24th November), the Biocodex Microbiota Institute sheds the light on the key role played by physician regarding information about the impact of antibiotics on microbiota and health.

Train the physicians: pass it on to their patients.

Engaging healthcare professionals (antibiotics prescribers) with tailor-made content.  During the WAAW campaign, Biocodex Microbiota Institute federates its physicians ‘community with two “hub” pages gathering all physicians’ tools (thematic folder, accredited training on dysbiosis and the impact of antibiotics, infographics to share with their patients, news, experts ‘interviews…).
 

Raising awareness of the impact of antibiotics on microbiota remains important. This two “hub” pages aim to provide physicians quick and ready-to-use material to improve their patients understanding of the importance of using antibiotics prudently.

Educate the lay public:  you can take action!

Hailed as one of the greatest medical advances of the 20th century, antibiotics have saved millions of lives. Today, they pose serious public health challenges: their excessive and inappropriate use leads to the emergence of numerous resistances, which, in the long term, could eventually make them ineffective. Moreover, they also can damage the microbiota by inducing a dysbiosis. For the lay public, the Institute investigates this ambivalence role with one “hub” page gathering all content on the impact of antibiotics on microbiota. 
 

From subsidiaries to the Biocodex Microbiota Institute passing through Beauvais manufacturing site, all Biocodex’s collaborators get involved!

For the WAAW campaign 2023, Biocodex Microbiota Institute website homepage, X, Facebook and LinkedIn accounts have turned blue. The Institute’s social networks are not the only ones… the Biocodex 9-hectare manufacturing and logistics center in Beauvais, near Paris, joined the color campaign by wearing blue during WAAW event. More than 30 spotlights have been placed to offer visitors and Biocodex collaborators a blue scenography. From November 18 to 24, the Institute invites Biocodex’s collaborators all over the world to join the campaign on social media thanks to a blue stamp they can put on LinkedIn.

#GoBlueForAMR.
 

BMI 23.49

According to the International Microbiota Observatory, more than 9 out of 10 (95%) people who repeatedly benefited from information from their healthcare professional had adopted specific behaviors to maintain a balanced microbiota. What about antibiotics? Well, according to the same study, only 1 in 3 patients said their healthcare professional had informed them that taking antibiotics could upset their microbiota balance. Because information provided by healthcare professionals is a game-changing vector of behavior, during the WAAW 2024 (18-24th November), the Biocodex Microbiota Institute sheds the light on the key role played by physician regarding information about the impact of antibiotics on microbiota and health.

Train the physicians: pass it on to their patients.

Engaging healthcare professionals (antibiotics prescribers) with tailor-made content.  During the WAAW campaign, Biocodex Microbiota Institute federates its physicians ‘community with two “hub” pages gathering all physicians’ tools (thematic folder, accredited training on dysbiosis and the impact of antibiotics, infographics to share with their patients, news, experts ‘interviews…).
 

Raising awareness of the impact of antibiotics on microbiota remains important. This two “hub” pages aim to provide physicians quick and ready-to-use material to improve their patients understanding of the importance of using antibiotics prudently.

Educate the lay public:  you can take action!

Hailed as one of the greatest medical advances of the 20th century, antibiotics have saved millions of lives. Today, they pose serious public health challenges: their excessive and inappropriate use leads to the emergence of numerous resistances, which, in the long term, could eventually make them ineffective. Moreover, they also can damage the microbiota by inducing a dysbiosis. For the lay public, the Institute investigates this ambivalence role with one “hub” page gathering all content on the impact of antibiotics on microbiota. 
 

From subsidiaries to the Biocodex Microbiota Institute passing through Beauvais manufacturing site, all Biocodex’s collaborators get involved!

For the WAAW campaign 2023, Biocodex Microbiota Institute website homepage, X, Facebook and LinkedIn accounts have turned blue. The Institute’s social networks are not the only ones… the Biocodex 9-hectare manufacturing and logistics center in Beauvais, near Paris, joined the color campaign by wearing blue during WAAW event. More than 30 spotlights have been placed to offer visitors and Biocodex collaborators a blue scenography. From November 18 to 24, the Institute invites Biocodex’s collaborators all over the world to join the campaign on social media thanks to a blue stamp they can put on LinkedIn.

#GoBlueForAMR.
 

Cesarean section (C-section) is a common mode of delivery worldwide. The global C-section rate remains at 21%, varying widely from 0.6% to 58.1% across regions. However, C-section delivery has been associated with an increased risk of adverse health outcomes, including autoimmune and metabolic disorders, altered gut microbiota and even neurodevelopmental disorders in infants ¹. Emerging research points to Vaginal Microbiota Transfer (VMT) as a prospective intervention to ameliorate the gut microbiota maturation and neurodevelopment in C-section babies. However, we are still debating on its safety and effectiveness.

How does VMT work? 

Two hours before the C-section, a wet gauze with sterile saline is placed in the lower vagina of women having a C-section. This gauze remains in situ for roughly an hour, and it’s removed 30 minutes before the administration of prophylactic antibiotics in preparation for the C-section delivery.

Immediately following birth, a trained nurse puts the vaginal gauze in contact with the newborn. The gauze is passed on their lips, face, chest, arms, legs, genitals, and bottom. Then, the nurse wipes their back. It takes about 15 seconds. The babies don't get a bath for 12 hours ².

What about VMT’s safety and effectiveness? 

A new research published in Cell Host & Microbes conducted a triple-blind randomized controlled trial to assess the safety and efficacy of VMT in improving neurodevelopment, gut microbiota, and metabolome of C-section babies ². The study enrolled 76 pregnant women that were scheduled for C-sections.

The newborns were randomly assigned to the VMT (n = 35) or control (n = 41) group. The neurodevelopment of the newborns was assessed with the Ages and Stages Questionnaire (ASQ-3) at 6 months of age, their gut microbiota and metabolomes were also analyzed. An additional 33 pregnant women planned for vaginal delivery were also included for comparison. 

In contrast to FMT (fecal microbiota transplantation), which is not advisable for DIY attempts and carries substantial risks, VMT stands out as a less perilous medical procedure that can be readily taught to delivery nurses and midwives. Healthcare professionals should consider VMT as a potential intervention to improve the gut microbiome and neurodevelopment of cesarean-born infants.

Do you feel more beautiful, healthier, and attractive when tanned? Unfortunately, your skin microbiota does not agree... And neither does your health!

So concludes a study ¹ on a group of 4 men and 17 women from Northern Europe who spent at least a week on vacation basking in the sun.

The day before their departure, the researchers took a skin sample from the most tanned part of the participants’ forearms in order to analyze the composition of their skin microbiota. They repeated this the day after the participants’ return (D1), 28 days later (D28), and then after 84 days (D84). 

To determine their phototype and changes in their tans, the scientists also measured the color of the skin on their “posteriors” (low exposure to sun) and forearms, both before and after sun exposure.

To each their own sun exposure...

The results?

Firstly, it was possible to classify the volunteers into three groups:

• The “tanning enthusiasts”, who spent a lot of time in the sun during their vacations;
• The “already tanned”, who had tanned skin before departure and kept it that way;
• The “wary”, who were minimally tanned before leaving and managed to protect themselves from the sun.

The researchers went on to report that in all the volunteers, three major bacterial phyla – Actinobacteria, Proteobacteria, and Firmicutes – accounted for 95% of all microorganisms.

However, on D1, just after returning from vacation, the “tanning enthusiasts” and the “already tanned” showed a skin microbiota depleted in Proteobacteria. 

While this reduction in diversity disappeared over time, and was non-existent by D28, the finding is important.

Potentially harmful changes in skin microbiota

Changes in the Proteobacteria content of the skin microbiota have already been observed in people suffering from psoriasis, eczema, and ​​diabetic foot ulcers.

Studies have also shown that a higher skin density of Proteobacteria is associated with better protection against allergy-related skin inflammation. 

These data therefore suggest that a Proteobacteria imbalance in the skin of those who tend to expose themselves to a lot of sun may lead to a deterioration in health.

Admittedly, this study has a number of limitations (small number of volunteers, women overrepresented, only indirect measurement of sun exposure, etc.) and its findings need to be confirmed by larger-scale studies. 

However, it does open up the possibility of one day using products based on certain beneficial bacteria (probiotics) to limit the deterioration of the skin microbiota during sun exposure.

Over the past decade, the therapeutic arsenal available to treat advanced melanoma has grown. Despite this, half of patients receive no benefit from anti-PD-1 immunotherapy. Combination therapy using anti-PD-1 (sidenote: Anti-PD-1 immunotherapy based on immune checkpoint inhibitors that target the PD-1 checkpoint, reversing the deactivation by the tumor of the recognition system associated with the PD-1 protein present on the surface of T lymphocytes. The immune system’s effectiveness against tumor cells is thus restored. ) and anti-CTLA-4 (sidenote: Anti-CTLA-4 immune checkpoint inhibitor that targets the CTLA-4 checkpoint ) improves response rates, but is associated with immune-related adverse events (irAEs). The gut microbiota regulates the immune system. So what about combining anti-PD-1 with fecal microbiota transplantation (FMT)? This option was explored in a multicenter phase I trial involving 20 patients (sidenote: aged 48 to 90 (average age of 75.5 years), including 12 men (60%) ) with unresectable or metastatic melanoma who had not previously received anti-PD-1 treatment. They received oral FMT (capsules) from a healthy donor (sidenote: three healthy male donors (average age of 35 years) provided the feces used for 4, 7, and 9 patients, respectively ) , followed seven days later by a first cycle of anti-PD-1 (sidenote: nivolumab or pembrolizumab ) .

Comparable safety

The trial’s primary endpoint was safety. FMT induced at most grade 1 or 2 adverse events (diarrhea, flatulence, etc.) in 8 patients (40%). Following anti-PD-1, 17 patients (85%) showed side effects, including 5 patients (25%) with grade 3 irAEs (2 arthritis, 1 fatigue, 1 pneumonia, 1 nephritis) which required temporary discontinuation of treatment. Compared with anti-PD-1 alone (79.5%-93.2% irAEs in phase III clinical trials, including 13.3%-34.0% grade 3-5 irAEs), combined treatment with FMT and anti-PD-1 did not increase the incidence of these events.

Potentially improved response

In terms of efficacy, the objective response rate of 65% (13 patients) was satisfactory and higher than that of anti-PD-1 alone (54%-63% in randomized phase III trials), although the small sample size and absence of a control group (anti-PD-1 only) limit interpretation of the results. The respective donor had no apparent effect on the outcome.

Long-term changes in gut microbiota

Regular sampling of the patients’ stools (sidenote: at baseline, immediately before anti-PD-1, then 1 month and 3 months after anti-PD-1 ) shows that the diversity of recipients’ gut microbiota only increases after FMT. In terms of composition, one week after FMT, the microbiota of all recipients more closely resembled those of their respective donors. However, this similarity subsequently regressed in future non-responders but increased in responders. 

One month after FMT, the flora of responders was enriched in immunogenic bacteria (sidenote: Ruminococcus, Eubacterium ramuleus, and Faecalibacterium ) and depleted in deleterious bacteria (sidenote: Clostridium methylpentosum, Enterocloster aldensis, Erysipelatoclostridium ramosum, and Enterocloster clostridioformis ) .

An effect on T lymphocytes?

The study also showed changes in patients’ plasma metabolites, with an increase in primary and secondary bile acids. After FMT, certain T lymphocytes (ICOS+CD8+) increased in the peripheral blood of responders only.

Lastly, mouse models treated with antibiotics prior to FMT confirm the role of FMT in increasing anti-PD-1 efficacy.

Asthma, allergic rhinitis, food allergies, and atopic dermatitis are often studied on their own, despite having many similar mechanisms (inflammatory responses, immunoglobulin E). Could something else they have in common be the gut microbiota, which matures in parallel with the infant immune system? To find out, data from 1,115 children included in the vast CHILD (sidenote: https://childstudy.ca/ ) longitudinal study were used: 592 children diagnosed with one or more allergic disorders after the age of 5, and 523 children with no signs of allergic sensitization. Regression analysis revealed several risk factors, such as male gender, paternal or maternal history, and antibiotic use before the age of one. Breastfeeding up to six months of age and Caucasian ethnicity appear to be protective.

Less mature gut microbiota

An analysis of stool samples collected at three months and one year of age revealed a delay in microbiota diversification in the children who subsequently developed allergies. Whereas control children had age-appropriate gut flora at age one, future allergic children showed a delay in the maturation of their microbiota. Less maturation of the microbiota at age one seems to be associated with an increased risk of allergic disorders at age five, regardless of the allergy.

Gut microbiota dysbiosis

A gut dysbiosis at age one also characterizes future allergic children: depleted levels of four bacterial species that produce short-chain fatty acids (butyrate-producing Anaerostipes hadrus, Fusicatenibacter saccharivorans and Eubacterium hallii, and acetate-producing Blautia wexlerae) and an increased abundance of five bacteria generally considered pathogenic (Eggerthella lenta, Escherichia coli, Enterococcus faecalis, Clostridium innocuum, and Tyzzerella nexilis). Enrichment in C. innocuum and T. nexilis is correlated with antibiotic use; the abundance of C. innocuum, E. lenta, E. faecalis, and T. nexilis depends on whether or not the baby is breast-fed at six months; while the abundance of C. innocuum and E. lenta is correlated with paternal atopy, and so on.

Metabolites to predict or prevent?

In parallel, the researchers identified 11 metabolic pathways significantly altered in at least two of the allergy diagnoses: nine deleterious pathways correlated mainly with E. coli, while two protective pathways were linked to the bacteria B. wexlerae, F. saccharivorans, A. hadrus, and E. hallii.
A metabolite analysis led to associations with age predicted by the gut microbiota: elevated trace amines (phenylethylamine, tryptamine, and tyramine) promoted inflammation and reduced butyrate production. Thus, the association between altered microbiota maturation and allergies at age five appears to be mediated by these metabolites, which may represent first-choice targets for predicting and/or preventing the development of pediatric allergies.