12 January - 20 June 2016

Neonatal gut microbiota and allergy risk

A study led by researchers from the University of California and the Henry Ford Health System in Detroit, published in Nature Medicine, suggests that babies with a particular type of gut microbiota are more likely to develop atopy (tendency to develop allergies) and asthma by the age of 2 and 4 respectively.

A study led by researchers from the University of California and the Henry Ford Health System in Detroit, published in Nature Medicine, suggests that babies with a particular type of gut microbiota are more likely to develop atopy (tendency to develop allergies) and asthma by the age of 2 and 4 respectively.

Fujimura et al. note that as atopy has recently been linked to depletions of bacterial diversity at 3 months of age, they hypothesised that distinct states of neonatal microbiota may exist and that these may influence the relative risk of allergy and asthma in later childhood.

Using 16S rRNA sequencing, the researchers analysed stool samples of 130 ‘neonates’, aged between 16 and 138 days with an average age of 35 days, as well as those from 168 ‘infants’, aged between 170 and 322 days with an average age of 201 days, all from a racially and socioeconomically diverse birth cohort. Using a multinomial mixture model, Fujimura et al. found three distinct Neonatal gut microbiota (NGM) states, which they designated NGM1, NGM2 and NGM3, and two distinct Infant gut microbiota (IGM) states, designated IGM1 and IGM2. At 2 years of age, “Predominantly Multisensitised” (PM) atopy was defined according to the pattern of blood specific-IgE responses to a set of 10 food and aeroallergens.  At 4 years of age, asthma was recorded by parental reporting of doctor diagnosis.

Fujimura et al. note that when using a conventional definition of atopy (with IgE levels >0.35 IU/ml), there was no difference in relative risk of having allergies or asthma between any of the 3 NGM states.  However when the PM atopy definition was used, neonatals with gut microbiota in the NGM3 state had a much higher relative risk of atopy at age 2. When considering asthma at age 4, the relative risk was even higher for NGM3 compared to NGM1 and NGM2 states. The study notes that the gender of the neonatals and the presence of detectable dog allergens in the home differed significantly across the groups but that even when adjusted for these confounding factors, the “relationship between NGM and atopy or asthma persisted”.

Fujimura et al. state that the NGM3 group had a lower abundance of certain bacteria, including Bifidobacteria, Lactobacillus and Faecalibacterium, and an increased abundance of some fungi, including Rhodotorula and Candida. The scientists found no difference between relative risk for atopy or asthma between the IGM1 and IGM2 groups.

Fujimura et al. also applied sterile faecal water from stools of the NGM3 groups ex-vivo to adult immune cells and found that this increased the proportion of CD4+IL-4+ cells (allergy-promoting immune cells) and decreased the ratio of CD4+IFNy+:CD4+IL-4+ (CD4+IFNy+ being cells which protect against allergy).  The authors note that when one particular metabolite, 12,13-DiHOME, which NGM3 samples contained higher levels of, was added to adult immune cells, a similar decrease in allergy-protective cells occurred.

In conclusion, Fujimura et al. note that neonatal gut microbiota can influence the susceptibility of children to atopy and asthma.  They propose that this may be due to changes in the gut microenvironment which influence the populations and functions of CD4+ T cells. They suggest that early interventions relating to gut microbiota might therefore offer a “viable strategy for disease prevention”.

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