乌鸦传媒

Use of antibiotics early in life was linked to an increased risk of atopic dermatitis, likely driven by gut microbiome disruption, according to data from the Canadian CHILD birth cohort.

Use of systemic antibiotics during the first year of life was associated with an increased risk of atopic dermatitis (adjusted OR 1.81, 95% CI 1.28-2.57, P<0.001), with the risk becoming non-significant when antibiotics were used after 1 year, reported Padmaja Subbarao, MD, of the Hospital for Sick Children in Toronto, and co-authors.

Furthermore, an increased number of antibiotic courses corresponded to a dose-response-like increased risk of atopic dermatitis (one course: aOR 1.67, 95% CI 1.17-2.38; two or more courses: aOR 2.16, 95% CI 1.30-3.59), they wrote in the .

Atopic dermatitis is the most common chronic inflammatory skin disease in both kids and adults, and is driven by genetic and environmental factors.

"Pediatric AD [atopic dermatitis] diagnoses are on the rise and often indicate broader dysregulation within immunological and skin barrier processes," Subbarao and team wrote. "Indeed, as a key feature of the the presentation of AD in early life is commonly followed by the sequential development of additional allergic diagnoses, specifically food allergies, asthma, and allergic rhinitis."

"Infancy is a period of pronounced development for a number of biological systems within the human body, and this coincides with dramatic shifts and expansion within the microbiome as it matures," they added. "Emphasizing the sensitivity of this time, microbiota perturbations early in life are often associated with long-term health consequences that extend beyond infancy."

Peck Ong, MD, of Children's Hospital Los Angeles, noted that while there may not be a definitive link between antibiotic use and atopic dermatitis, caution could always be exercised.

"I think one other message that this study provides is that during the early stage of infancy, pediatricians will be more careful in using antibiotics," he told 乌鸦传媒. "If it's not necessary, then we advise refraining from using it, because there is some evidence that that may increase atopy or allergic conditions."

Subbarao and colleagues previously found that requiring healthcare utilization that occurred before the age of 18 months were associated with an increased risk of allergic diseases, including atopic dermatitis, at age 5 years.

In this study, the authors collected stool samples from the subset of infants with a complete antibiotic history and those with a clinical evaluation for atopic dermatitis at age 5 to understand whether microbial features sensitive to antibiotic exposure may influence later atopic dermatitis. They compared species abundance at 1 year and found that 18 species of 72 tested were significantly altered in those with atopic dermatitis and 15 were altered by antibiotic exposure.

Of these, four overlapping species were significantly altered in patients with both antibiotic exposure during the first year of life and atopic dermatitis at 5 years -- Bifidobacterium bifidum (mean relative abundance 5.03%), Bifidobacterium longum (mean relative abundance 14.87%), Eubacterium rectale (mean relative abundance 1.17%), and Tyzzerella nexilis (mean relative abundance 0.20%).

Subbarao and team noted that Bifidobacterium are key to breaking down milk among breastfeeding infants.

"Specifically, fecal acetate produced by Bifidobacterium is regarded as a biomarker for bifidogenic activity, microbiota health in early life, and risk for atopy and wheezing, while butyrate may be a marker for healthy maturation of the gut microbiota as children age and their diet diversifies," they wrote. "As the gut microbiota changes over time, early colonizing bacteria such as Bifidobacterium lessen and provide the cross-feeding substrates of acetate and lactate for butyrate-producing bacteria like Faecalibacterium, Roseburia, and Eubacterium, representative of more adult-like butyrogenic microbiota [that] may be important for healthy maturation of the immune system."

Ong also pointed out that using stool samples may help in predicting other conditions down the line.

"It's now well known that development of atopic dermatitis or eczema is the first step in having allergic conditions," he said. "So I think the current thinking is that if we can prevent the first step, maybe we can prevent the other problems like food allergy, asthma, and allergic rhinitis."

"If we can look at the stool microbiome at a year old, we may be able to predict [that] this is a child who is high at risk for developing eczema, and then that leads to subsequent intervention," he added. "So I think what the study provides us is a biomarker that's easily obtained because stool samples are easily obtained."

Subbarao and colleagues used data from the longitudinal, prospective, general population CHILD birth cohort that tracked infants to 5 years of age and beyond. A total of 3,621 pregnant women from four cities -- Vancouver, Edmonton, Winnipeg, and Toronto -- were enrolled along with eligible infants (n=3,455) who had no congenital abnormalities and were born at a minimum of 34 weeks of gestation.

Several questionnaires related to environmental exposures and general health were administered at recruitment; prenatally; at 3, 6, 12, 18, 24, and 30 months; and at 3, 4, and 5 years. At ages 1, 3, and 5 years, parents completed questionnaires validated in the International Study of Asthma and Allergies in Childhood.

The researchers noted that their cohort is not necessarily representative of the general Canadian population, and there may be biases in the population, such as urban and higher-income families, maternal history of atopy, particular kinds of infant respiratory infections, and high concurrent risk for recurrent wheeze and atopic disorders.

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