Fecal microbiome and food allergy in pediatric atopic dermatitis: A cross-sectional pilot study

Background: Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). Methods: Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. Results: Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). Conclusions: In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings

The infant gut microbiome and resistome in health and disease

In this thesis, we describe the development of the infant gut microbiome and resistome, identify important environmental and nutritional drivers of this development and study the gut microbiome and microbial networks in relation to health and disease. We have shown that mode of delivery impacts the composition of the gut microbiome, with infants born by caesarean section carrying a higher abundance of potential pathogens such as Klebsiella and Enterococcus species in their gut. Interestingly, we could associate an increased abundance of these gut bacteria at one week of life with a higher susceptibility to respiratory tract infections in the first year of life. Next, we have established that even a short course of early-life broad-spectrum antibiotics has long-term effects on the developing infant gut microbiome, especially selecting for potential pathogenic bacteria and increasing the abundance of antimicrobial resistance genes for a prolonged period of time. In case of suspected early-life infection, we strongly advise treatment with the antibiotic combination consisting of penicillin + gentamicin, as this has the least detrimental impact on microbiome and resistome development, when compared to the commonly used combinations co-amoxiclav + gentamicin or amoxicillin + cefotaxime. Finally, we modelled microbial networks across body sites, spanning the gut and respiratory tract, and found that infants with less robust networks had a higher susceptibility to respiratory tract infections. Altogether, the results of this thesis provide insights into multiple environmental drivers of the infant gut microbiome and resistome development and how these relate to health later in life

Rectal swabs are a reliable proxy for faecal samples in infant gut microbiota research based on 16S-rRNA sequencing

Rectal swabs are potentially a valuable method for monitoring the gut microbiome in research and clinical settings, where it is important to adhere to strict timing, or where acute sampling is needed. It is currently unknown whether rectal swabs give comparable results to faecal samples regarding microbiota community composition in neonates and infants. To study how well the two sampling methods correlate in infants, we compared the 16S-rRNA-based sequencing results of 131 paired rectal swabs and faecal samples collected from 116 infants at two timepoints in early life. The paired samples were highly comparable regarding both diversity and overall community composition, and strongly correlated on taxonomical level. We observed no significant nor relevant contribution of sampling method to the variation in overall gut microbiota community composition in a multivariable model. Our study provides evidence supporting the use of rectal swabs as a reliable proxy for faecal samples in infant gut microbiota research

Rectal swabs are a reliable proxy for faecal samples in infant gut microbiota research based on 16S-rRNA sequencing

Rectal swabs are potentially a valuable method for monitoring the gut microbiome in research and clinical settings, where it is important to adhere to strict timing, or where acute sampling is needed. It is currently unknown whether rectal swabs give comparable results to faecal samples regarding microbiota community composition in neonates and infants. To study how well the two sampling methods correlate in infants, we compared the 16S-rRNA-based sequencing results of 131 paired rectal swabs and faecal samples collected from 116 infants at two timepoints in early life. The paired samples were highly comparable regarding both diversity and overall community composition, and strongly correlated on taxonomical level. We observed no significant nor relevant contribution of sampling method to the variation in overall gut microbiota community composition in a multivariable model. Our study provides evidence supporting the use of rectal swabs as a reliable proxy for faecal samples in infant gut microbiota research

Microbial community networks across body sites are associated with susceptibility to respiratory infections in infants.

Respiratory tract infections are a major cause of morbidity and mortality worldwide in young children. Concepts such as the gut-lung axis have highlighted the impact of microbial communities at distal sites in mediating disease locally. However, little is known about the extent to which microbial communities from multiple body sites are linked, and how this relates to disease susceptibility. Here, we combine 16S-based rRNA sequencing data from 112 healthy, term born infants, spanning three body sites (oral cavity, nasopharynx, gut) and the first six months of life. Using a cross-niche microbial network approach, we show that, already from the first week of life on, there is a strong association between both network structure and species essential to these structures (hub species), and consecutive susceptibility to respiratory tract infections in this cohort. Our findings underline the crucial role of cross-niche microbial connections in respiratory health.ISSN:2399-364

Mode of delivery modulates the intestinal microbiota and impacts the response to vaccination

The gut microbiota in early life, when critical immune maturation takes place, may influence the immunogenicity of childhood vaccinations. Here we assess the association between mode of delivery, gut microbiota development in the first year of life, and mucosal antigen-specific antibody responses against pneumococcal vaccination in 101 infants at age 12 months and against meningococcal vaccination in 66 infants at age 18 months. Birth by vaginal delivery is associated with higher antibody responses against both vaccines. Relative abundances of vaginal birth-associated Bifidobacterium and Escherichia coli in the first weeks of life are positively associated with anti-pneumococcal antibody responses, and relative abundance of E. coli in the same period is also positively associated with anti-meningococcal antibody responses. In this study, we show that mode of delivery-induced microbiota profiles of the gut are associated with subsequent antibody responses to routine childhood vaccines

Author Correction : Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life (Nature Communications, (2019), 10, 1, (4997), 10.1038/s41467-019-13014-7)

The original version of this Article contained an error in the number of unique bacterial taxa identified by whole genome shotgun sequencing, which was incorrectly given as 137 instead of 119. This has been corrected in both the PDF and HTML versions of the Article

Mode of delivery modulates the intestinal microbiota and impacts the response to vaccination.

The gut microbiota in early life, when critical immune maturation takes place, may influence the immunogenicity of childhood vaccinations. Here we assess the association between mode of delivery, gut microbiota development in the first year of life, and mucosal antigen-specific antibody responses against pneumococcal vaccination in 101 infants at age 12 months and against meningococcal vaccination in 66 infants at age 18 months. Birth by vaginal delivery is associated with higher antibody responses against both vaccines. Relative abundances of vaginal birth-associated Bifidobacterium and Escherichia coli in the first weeks of life are positively associated with anti-pneumococcal antibody responses, and relative abundance of E. coli in the same period is also positively associated with anti-meningococcal antibody responses. In this study, we show that mode of delivery-induced microbiota profiles of the gut are associated with subsequent antibody responses to routine childhood vaccines