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Maturation of the gut microbiome and risk of asthma in childhood.

ABSTRACT: The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.

SUBMITTER: Stokholm J

PROVIDER: S-EPMC5762761 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Maturation of the gut microbiome and risk of asthma in childhood.

Stokholm Jakob J Blaser Martin J MJ Thorsen Jonathan J Rasmussen Morten A MA Waage Johannes J Vinding Rebecca K RK Schoos Ann-Marie M AM Kunøe Asja A Fink Nadia R NR Chawes Bo L BL Bønnelykke Klaus K Brejnrod Asker D AD Mortensen Martin S MS Al-Soud Waleed Abu WA Sørensen Søren J SJ Bisgaard Hans H

Nature communications 20180110 1

The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 year ...[more]

PMID: 29321519

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Project description:IntroductionGut microbiome plays a crucial role in maintaining human health and is influenced by food intake, age, and other factors.MethodsIn this study based in Korea, we examined the bacterial taxonomic composition of the gut microbiota in infants (≤ 1 year), toddlers (1-<4 years), and school-aged children (4-13 years) and compared them with those of healthy adults to investigate the microbiota changes in early life and their association with the resistome. We used whole metagenome sequences obtained by Illumina HiSeq sequencing and clinical information of 53 healthy children, and sequence data of 61 adults from our previous study.ResultsOur results indicate that the bacterial proportion of the gut in the population ranging from infants to adults forms three clusters: the Ruminococcus-Eubacterium (G1), Bifidobacterium-Escherichia (G2), and Bacteroides-Faecalibacterium (G3) groups. The gut microbiota of infants and toddlers (100% of infants and 85% of toddlers) constituted mostly of G2 and G3 groups, whereas 90% of adults showed G1-type gut microbiota. School-aged children showed a transitional gut microbiota composition of both infants and adults (31%, 38%, and 31% in G1, G2, and G3, respectively). Notably, the three clusters of microbiota showed significantly different patterns of bacterial diversity (p < 0.001): G2 showed the lowest Shannon index, followed by G3 and G1 (1.41, 2.08, and 2.48, respectively; median Shannon index). When combined with the adult group, alpha diversity showed a positive correlation with age (R2 = 0.3). Furthermore, clustering the composition of antibiotic resistance genes (ARG) identified two clusters (A1 and A2), and most of G1 (95%) and G3 (80%) belonged to A1. However, G2 showed the least diversity and the highest abundance of ARGs. Nine ARG families showed a significant difference among age groups; three tetracycline resistance genes, tet32, tetO, and tetW, showed a positive correlation, and six other genes, ampC, TEM, ileS, bacA, pmr transferase, and cepA, showed a negative correlation with age.DiscussionIn conclusion, our results highlighted that a delayed persistence of the Bifidobacterium-dominant enterotype with a lower bacterial diversity was observed in Korean children up to 13 years of age, which suggests a different maturation process with a delayed maturation time.

Project description:BackgroundDespite substantial evidence on the contribution of the diversity of the gut microbiome to the pathogenesis of asthma and allergic diseases, little is known about their relationship with asthma severity and/or clinical phenotypes. We analyzed the difference in composition of the gut microbiome between subjects with asthma and healthy subjects and explored its role in the development of asthma.MethodsFecal samples from 15 subjects with severe asthma (SA), 14 with non-severe asthma (NSA), and 15 healthy subjects were assessed by 16S ribosomal RNA gene sequencing methods to identify the gut bacterial composition.ResultsCompared with those in the NSA group, patients in the SA group had a higher dose of inhaled corticosteroids, and there were more atopic subjects (60% vs. 35.7%, respectively). No significant differences were found at the phylum level either in operational taxonomic unit numbers or in diversity scores among the SA, NSA, and healthy groups. However, at the family level, the relative abundance of Acidaminococcaceae in the SA group was remarkedly lower than that in the group with healthy subjects (P<0.05). Furthermore, Veillonellaceae and Prevotellaceae were significantly more common in samples from the SA group than in those from the NSA group (P<0.05). In the SA group, positive correlations were observed between the relative abundance of Veillonellaceae and mid-expiratory flow 25% (MEF25%) predicted (r=0.538, P=0.047), as well as between the relative abundance of Acidaminococcaceae and body mass index (r=0642, P=0.010). Principal component analysis suggested that the relative abundances of Acidaminococcaceae and Prevotellaceae were associated with severe asthma. Moreover, we found that class Betaproteobacteria, order Burkholderiales, and family Alcaligenaceae were significantly different among the groups defined by serum immunoglobulin E (IgE) levels.ConclusionsOur findings suggest that altered gut microbiome compositions are involved in the severity of asthma and that there are specific bacteria related to different asthma phenotypes in terms of serum IgE levels.

Project description:IntroductionVery Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants' gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models.MethodsParents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin).ResultsNineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such as Veillonella dispar, Enterococcus, Escherichia coli, and Rumincococcus to later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years.DiscussionThese preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).

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Maturation of the gut microbiome and risk of asthma in childhood.

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Maturation of the gut microbiome and risk of asthma in childhood.

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