Association between infant intestinal microbiome and respiratory diseases of childhood

In a recent study published in The Lancet Microbe, researchers performed a systematic review to assess the association between the composition of infant gut microbiota and childhood respiratory disorders.

Background

Respiratory disorders of childhood such as asthma and recurrent wheezing have caused considerable mortality and morbidity among children.  Previous studies using animal models have reported on the role of infant gut microbiota in pulmonary immunological development and in establishing vulnerability to asthma and respiratory infections in human beings.

About the study

In the present study, researchers systematically reviewed existing literature to explore the association between intestinal microbiome composition in infancy (below one year of age) measured by genomic sequencing and the development of childhood respiratory disorders such as respiratory infections, asthma or recurrent wheezing.

The systematic review was performed following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Data were obtained from databases such as Cochrane, MEDLINE, Web of Science, Scopus and Embase for full-text English articles published between 1 January 2010, and 27 April 27 2021, using search terms such as intestine, infancy, respiratory disease and microbiota.

For studies of in vitro type, if they included non-primary research, or if the exposure of the outcome was irrelevant to the primary research question, they were excluded from the systematic review. Two reviewers independently screened and critically appraised data, and disagreements were resolved by a third reviewer. The methodological quality of all the studies was assessed, the STROBE (strengthening the reporting of observational studies in epidemiology) checklist was used for metagenomic data and the NOS (Newcastle-Ottawa scale) was used for bias evaluation.

Results

A total of 7347 studies were initially identified from the databases and one potentially eligible study was identified from other sources, of which, 2589 duplicate articles were excluded. From the remaining 4759 titles and abstracts screened, 4648 were excluded based on the eligibility criteria. As a result, the full text of 111 studies was evaluated, and 100 studies were excluded.

The reasons for exclusion were: (i) they were not peer-reviewed or original research (n=42), (ii) in vitro studies (n=7), (iii) child intestinal microbiome was not the exposure (n=17), (iv) the outcome was not a respiratory disease (n=17), (v) intestinal microbiome was not assessed before respiratory diseases’ onset (n=7), (vi) intestinal microbiome was first assessed after one year of age (n=2), (vii) microbiome was not assessed by next-generation sequencing or (viii) small patient subset (n=5), sample size below five participants (n=3).

Finally, 11 studies were considered for the systematic review comprising cohort studies (n=8) and case-control studies (n=3) and the median sample size among the studies comprised 319 individuals. 16S ribosomal ribonucleic acid (rRNA)-targeted amplicon sequencing was performed in all studies to determine the intestinal microbiome. Four studies, one study, and six studies were of poor quality, fair quality and good quality, respectively.

Two (out of seven) studies reported that greater intestinal α-diversity microbiota within the first 12 months of age was associated significantly with the absence of atopic wheezing at one year of age and the absence of asthma at five to six years of age. A study reported a positive association between intestinal microbiome maturity at five weeks of age and asthma risk among children aged six to eleven years. In contrast, two of the included studies reported that an immature intestinal microbiome at one year of age was associated with a greater asthma risk at five to six years of age.

In addition, an association was observed between the lower Lachnospira abundance at three months of age but greater Lachnospira abundance at one year of age and atopic wheezing and asthma at one year to six years of age. A study showed similar associations for Veillonella species whereas two studies reported otherwise.

An association was observed between a greater abundance of Rhodotorula and Candida and lower Malassezia abundance at one month of age and greater Pichia kudriavzevii abundance at three months of age and atopic wheezing and asthma at four to five years of age. However, another study found no such associations. A study demonstrated a higher incidence of pulmonary disorders at one year of age in cases of lower Bifidobacterium abundance and higher Enterococcus and Klebsiella abundance at one week of age.

The study results were heterogeneous; however, on the whole, lower abundance of Bifidobacterium species in stool samples obtained at one month to three months of age and a lower abundance of Faecalibacterium, Roseburia, and Ruminococcus species in stool samples obtained at three months to one year of age were associated with atopic wheezing and asthma at one year to six years of age.

Overall, the study findings demonstrated an association between low α-diversity and abundance of specific intestinal microbiota (Faecalibacterium, Bifidobacterium, Roseburia and Ruminococcus) with respiratory diseases in childhood. However, results were inconsistent and further research with larger sample populations and standardized and uniform outcomes, follow-up periods and analysis tools are warranted for identifying targets to prevent respiratory diseases of childhood.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.