Research highlights the gut–lung axis as a potential target for preventive strategies.
A birth cohort study has found that neonatal gut microbiota composition during the first week of life is significantly associated with later hospital admissions for viral lower respiratory tract infections.
Findings of the UK-based study – one of the most comprehensive analyses of the gut–lung axis in early life to date – have been published in The Lancet Microbe, and have potential implications for early-life microbial interventions aimed at preventing severe respiratory illness in infants.
“This study, to our knowledge, is the first to show that first-week gut microbiota composition was independently associated with reduced rates of viral lower respiratory tract infections hospital admission in the first two years of life for a subgroup of babies delivered vaginally (with higher relative abundance of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium adolescentis, and Bacteroides dorei, and lower relative abundance of Enterococcus faecalis and Bifidobacterium breve) compared with all other babies,” the authors wrote.
The prospective Baby Biome Study (BBS) followed more than 1000 neonates with sequenced stool samples taken within the first week of life and linked to NHS hospital admission data over the first two years.
Researchers found that higher alpha diversity in the gut microbiome, a marker of a richer and more balanced microbial ecosystem, was associated with a reduced risk of vLRTI-related hospitalisation.
Microbial community structure also appeared to play a critical role. Babies with gut microbiota dominated by B. longum (cluster 3), found exclusively in vaginally born infants, had significantly lower rates of hospitalisation compared to those with either mixed microbiota (cluster 1) or B. breve dominance (cluster 2).
The adjusted hazard ratios for clusters 1 and 2 were 3.1 and 2.8, respectively, when compared with cluster 3.
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The study adjusted for key confounders including mode of delivery, gestational age, sex and comorbidities, supporting the robustness of the associations observed. Nearly all babies in the cohort were born at term and were otherwise healthy, suggesting that microbiota differences alone may help explain disparities in vLRTI severity.
The study also showed that not all babies born vaginally showed lower rates of disease, with some showing similar rates of vLRTI admissions to babies born by caesarean section. This included neonates with mixed- or B. breve dominated gut microbiota, when compared to vaginally born babies who had a first-week B. longum dominated gut microbiota.
“These findings challenge the idea that vaginal birth is always associated with lower rates of disease, at least regarding vLRTI hospital admissions, hinting that the link is more nuanced,” the authors wrote.
“Our study suggests that some bacterial species or combinations of species, as early as the first week of life, could be of interest for vLRTI prevention interventions.”
The researchers noted there was a strong interest in modifying the early gut microbiota as a prevention strategy for childhood diseases, with studies providing some evidence that modulating the gut microbiota in the first months of life might prevent childhood respiratory infections.
“However, no conclusions have been reached regarding the optimal intervention age or probiotic composition,” they wrote.
“Moreover, no study used naturally occurring commensal (non-probiotic) bacteria identified as having protective effects against childhood respiratory diseases in observational studies, such as B. longum.
“Our work shows that gut microbiota patterns associated with reduced rates of vLRTI admission can be detected as early as the first week of life. Neonatal microbiota markers might therefore be used in the future, to stratify patients at risk for childhood diseases and guide probiotic selection in clinical trials.”
Other preventive strategies include vaginal seeding and perinatal maternal faecal transplants.
“These approaches, which have sparked controversies regarding their risk-and-reward balance, currently aim to expose babies born by caesarean section to more vaginal birth-like gut microbes and reduce subsequent disease,” the researchers wrote.
“However, our study challenges the idea that exposing babies born by caesarean section to the maternal gut and vaginal microbiota might reduce the risk of vLRTI hospital admission in childhood.
“We observed that only babies born vaginally with cluster 3 (B. longum dominated) microbiome, showed lower rates of disease, and other babies born vaginally had similar disease incidence when compared with babies born by caesarean section.”
