Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting

Abstract

BackgroundAsthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment.ObjectiveWe sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting.MethodsWe conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography.ResultsAs previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze.ConclusionsOur findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.

Exposure to sewage water and the development of allergic manifestations in Finnish children

“…Because earlier studies suggest that the gut microbiota composition before the age of 1 year can predict later IgE sensitization and allergic diseases, we analyzed the children below and above 1 year of age at the time of exposure separately. In the children below the age of one at the time of the water accident, SPT positivity at 5 years of follow‐up was decreased in Nokia; SPT at 2 years was positive in 7 of 56 Nokia children and in 12 of 47 Kangasala children (OR 0.417, 95% CI 0.149‐1.165; P = 0.126), and at 5 years in 10 of 44 Nokia children and in 17 of 35 Kangasala children (OR 0.311, 95% CI 0.118‐0.820; P = 0.019).…”

“…In humans, evidence supporting the hygiene hypothesis is mainly epidemiologic and the mechanisms are not completely understood. Recent studies suggest that the composition of the gut microbiome at early age is an important determinant of the later risk of allergic diseases …”

The Role of Lung and Gut Microbiota in the Pathology of Asthma

“…In an ovalbumin (OVA)-induced mouse model of airway inflammation, supplementation of a fecal slurry from an infant who developed asthma transplanted into germ-free mice with representative species from Lachnospira, Veillonella, Faecalibacterium, and Rothia genera decreased airway inflammation (Arrieta et al, 2015). In another human birth cohort study, Ecuadorian children with an increase in the relative abundance of Streptococcus and Bacteroides species and decrease in Bifidobacterium species and Ruminococcus gnavus in fecal samples at 3 months of age have a higher risk of developing atopy and wheeze at age 5 years (Arrieta et al, 2018). Finally, among neonates from the United States grouped into three clusters according to the composition of the gut microbiota, those with the lowest relative abundance of Bifidobacteria, Akkermansia, and Faecalibacterium genera and a higher relative abundance of Candida and Rhodotorula fungi have the highest risk of developing atopy and asthma (Fujimura et al, 2016) (Figure 3).…”

“…It remains unclear whether fungi colonize the healthy adult gut or are simply detected in sequencing studies as transient oral or food-derived fungi (Auchtung et al, 2018), but even transient colonizers of the gut have the potential to impact microbial community ecology and host immune responses (Hallen-Adams and Suhr, 2017). Although the mechanisms involved were not explored, two recent studies in human birth cohorts from the United States and Ecuador have identified fungal dysbiosis as a key feature of infant gut microbiota signatures associated with the development of high-risk asthma phenotypes in childhood (Fujimura et al, 2016;Arrieta et al, 2018). The specific signatures of fungal dysbiosis associated with asthma and related phenotypes differed in these studies, but it is notable that fungal dysbiosis was much more striking than bacterial dysbiosis in both studies.…”

Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research

“…But in most cases when dysbiosis is mentioned in eukaryotic (and bacterial) microbiome research, nobody has a clue what the cause or effect is (Arrieta et al. ). Most dysbiosis statements are bet‐hedging, as captured by the quote in Table : “dysbiosis” might be a cause, but then again it might be a consequence.…”