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December 13, 2021
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Study reveals new understanding of food protein-induced allergy pathophysiology in infants

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The development and resolution of food protein-induced allergic proctocolitis in the infant gut microbiome highlights the underlying role of bacterial taxa in the pathophysiology of the allergy, according to a presentation.

“We see key differences that precede disease onset and persist after resolution suggesting that maybe there’s an ongoing mechanism there that may be part of the key to why these kids are actually more likely to be allergic,” Victoria Martin, MD, of Massachusetts General Hospital in Boston, said at North American Society for Pediatric Gastroenterology, Hepatology & Nutrition Annual Meeting. “From a clinical perspective, I’d encourage all of you to read the guidelines, to make sure that you’re proving that kids have this disease before you put them on diet restriction for a long time. And even if they improve on diet restriction, to consider reintroducing milk, protein and anything else you’ve restricted early and often, and to consider other allergen induction, even when they’re young.”

In a nested, case-control study, Martin and colleagues used 1 week to 1 year of age 16S ribosomal RNA gene sequencing — part of the Gastrointestinal Microbiome and Allergic Proctocolitis Study — to assess 954 longitudinal samples from 160 infants. Of these, 81 had food protein-induced allergic proctocolitis (FPIAP) — also known as cow’s milk protein allergy — and 79 were matched controls.

Investigators used multivariate modeling controlled for infant diet, mode of delivery, age and probiotics use to find linear associations between FPIAP and microbial features after the adjustment of multiple comparisons.

Martin and colleagues found infants who were vaginally delivered had a greater abundance of Bacteroides. In addition, those who received breast milk had a greater abundance of Bifidobacterium. The overall bacterial richness increased over the first year. Investigators noted differences in the gut microbiome of infants with FPIAP, the most significant being a greater amount of an unclassified genus of Enterobacteriaceae. During the symptomatic period, Martin and colleagues noted a lower abundance of an unknown family of Clostridiales.

“We found significant taxonomic difference between infants with FPIAP and healthy controls, particularly the Enterobacteriaceae, Clostridiales and Lactobacillus species,” Martin said. “A machine learning approach identified those same differences in an independent way.”

In addition, they noted other differences in taxonomy across symptom states such as apparent dysbiosis before FPIAP symptom onset.

“We’re interested in some biomarker identification and looking at serology, and really understanding sensitization. I hope that with some metagenomic sequencing to really drill down to the strain level,” Martin concluded. “We can have a new start to understanding the pathophysiology of this disease and maybe also start to think about a paradigm shift away from diet restriction as our management strategy and toward perhaps dysbiosis prevention and water treatment.”