A new study published in the Nature Communications Journal examines the association between the maturation of the infant gut microbiome and the infant immune system.
Study: Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease. Image Credit: PhonlamaiPhoto/Shutterstock.com
Allergies are increasing in prevalence worldwide, along with changes in social and ecological conditions that could impact the human microbiome. The microbiome is established in early life, soon after birth, but undergoes several changes while it matures.
Risk factors for allergies and microbiota alterations have much in common, including the mode of delivery, the rural or urban lifestyle, dietary patterns, and antibiotic use. A healthy microbiome's maturation also accompanies the immune system's maturation.
Four types of allergy share the same etiology, with raised immunoglobulin E (IgE) and inappropriately activated type 2 inflammatory responses. The four conditions comprise atopic dermatitis, asthma, food allergy, and allergic rhinitis. They also follow a pattern in their onset called the Allergic March.
This phenomenon motivated the current study that looked at all four in parallel in association with their underlying microbiome changes.
What did the study show?
The study used detailed data from the prospective longitudinal CHILD cohort of over 1,100 children followed up from birth.
The findings show that the four allergic conditions are consistently linked to certain microbiome changes and early-life influences in children aged five.
After adjustment for confounding factors, the scientists found that males were at 85% higher risk, while it was increased by 60% in those with a parental history of atopic disease.
The greatest increase in risk was with antibiotic use before the age of one year, at over twice the baseline risk. Infants who were breastfed to any extent up to six months of age, and Caucasian infants, had a lower chance, however.
Notably, infant gut microbiome maturation is marked by increased microbial diversity over the first year of life, as different species show changes in their growth rate to become more or less abundant.
"This process is so linked to early-life development that the composition of the infant microbiota alone can accurately predict an infant's chronological age."
A subset of children, including about half the subset, had their gut microbiome maturation pattern analyzed by shotgun metagenomics and metabolomics. This showed that maturation at one year was linked to allergies in childhood.
That is, infants who showed lower gut microbiota diversity at one year of age, characteristic of delayed gut microbiome maturation, had a higher risk of allergy at five years.
All the children with any of these four allergies at age five were found to have a lower microbiota-predicted period at one year compared to those without allergies. Both these impairments were linked by a common pathway.
Children with a history of allergy at five years showed specific changes in the abundance of nine species, such as a reduction in Anaerostipes hadrus, Fusicatenibacter saccharivorans, but increases in Eggerthella lenta, and Escherichia coli, among others.
Some of these were further linked to specific exposures, such as antibiotic use, breastfeeding, and atopic history in the father.
This was taken forward to identify a baseline array of impaired functional and metabolic pathways altered in children with allergies.
These led to reduced mucosal integrity via mucous degradation by reducing key cysteine disulfide bonds, higher oxidative stress, decreased secondary fermentation of undigested or semi-digested products in the gut, and raised levels of trace biogenic amines.
Trace amines (TA) include phenylethylamine, tryptamine, and tyramine, all of which bind to TA-associated receptors (TAARs) on intestinal and immune cells. When they increase in concentration, they may promote chronic inflammation.
Thus, the restriction of TA abundance via microbiota shifts might be a key element of immune tolerance developing during infancy.
The infant gut microbiome's maturation thus alters the infant's functional and metabolic profile. Moreover, butyrate, an important short-chain fatty acid (SCFA) produced by secondary fermentation, was associated with F. saccharivorans and A. hadrus. This is known to be key to immune tolerance.
Bacterial species found in higher abundance in children with allergies are associated with adverse health outcomes and may become pathogenic. Interestingly, many of these characteristics are shared by the metabolites, which also exist at higher levels in these children.
Thus, the shift in these pathways appears to be the connecting link between early delay in gut microbiome maturation at one year and a diagnosis of one of these allergies at the age of five.
"Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease."
What are the implications?
"Our findings identify common, host-microbiome mechanisms associated with the development of clinically distinct allergic disorders. Prioritizing preventive strategies and therapeutic intervention to modify these host-microbe interactions during infancy may have lasting benefits for preventing pediatric allergic diseases."
These epidemiological associations were extracted from a subset of the CHILD cohort.
More research will be required to underpin these analyses, taking account of natural differences between gut microbiome composition in different individuals and geographical locations.
However, the scientists provided a greater understanding of how the infant gut microbiome could show alterations that predict and partly explain the future development of childhood allergies.