Pediatric non-IgE-mediated food allergy is characterized by distinct microbiome-inflammation relationships rather than a single dysbiotic signature, with a specific inflammatory microbiome endotype marked by elevated fecal calprotectin and EDN alongside enrichment of Veillonellaceae and depletion of Bifidobacteriaceae and Lachnospiraceae.
Key Findings
Results
Patients with non-IgE-mediated food allergy showed higher mean relative abundances of several bacterial genera compared to healthy controls.
Thirty pediatric patients with non-IgE-mediated food allergy were compared to fifteen healthy control children.
Gut microbiota profiling was performed by 16S rRNA gene sequencing targeting the V3-V4 region.
Higher mean relative abundances of Bacteroides, Faecalibacterium, Alistipes, Parabacteroides, and Sutterella were observed in patients compared to healthy controls.
Healthy children showed higher mean relative abundances of Pseudobutyrivibrio, Roseburia, Bifidobacterium, Collinsella, Clostridium, Eubacterium, Streptococcus, and Barnesiella.
Results
Several bacterial genera were detected exclusively in the allergy cohort and not in healthy controls.
Escherichia-Shigella, Agathobacter, and Enterococcus/Streptococcus were detected only in the allergy cohort.
These genera were absent from the healthy control group.
This finding suggests potential allergy-specific microbial colonization patterns.
Results
Shannon diversity index was higher in patients with non-IgE-mediated food allergy compared to healthy controls, and was further elevated in specific patient subgroups.
Shannon diversity was higher in patients compared to controls overall.
Shannon diversity was significantly higher in the subgroup of patients with elevated fecal calprotectin (p = 0.028).
Shannon diversity was significantly higher in patients with previous antibiotic exposure (p = 0.015).
Shannon diversity was significantly higher in patients with atopic dermatitis (p = 0.021).
Results
A distinct inflammatory microbiome endotype was identified among allergy patients stratified by inflammatory biomarkers.
Stratification according to inflammatory biomarkers identified a distinct inflammatory microbiome endotype.
This endotype was characterized by increased fecal calprotectin and eosinophil-derived neurotoxin (EDN).
The endotype featured enrichment of Veillonellaceae and depletion of Bifidobacteriaceae and Lachnospiraceae.
Fecal calprotectin and EDN were investigated as inflammatory biomarkers alongside fecal IgA.
Results
Veillonella abundance was positively associated with both fecal calprotectin and eosinophil-derived neurotoxin (EDN).
Correlation analyses revealed positive associations between Veillonella abundance and fecal calprotectin.
Positive associations were also found between Veillonella abundance and EDN.
These associations link a specific bacterial genus to two distinct markers of intestinal and eosinophilic inflammation.
Fecal calprotectin and EDN were used as non-invasive surrogate markers of gastrointestinal inflammation.
Background
Non-IgE-mediated food allergy is characterized by delayed gastrointestinal manifestations and lacks reliable non-invasive biomarkers.
The condition is distinguished by delayed gastrointestinal manifestations rather than immediate IgE-mediated reactions.
There is an absence of reliable non-invasive biomarkers for this condition.
Increasing evidence suggests gut microbiota may contribute to disease pathogenesis.
The study aimed to characterize gut microbiome composition and its association with fecal calprotectin, EDN, and IgA.
What This Means
This research examined the gut bacteria of 30 children diagnosed with non-IgE-mediated food allergy — a type of food allergy that causes delayed stomach and intestinal symptoms rather than immediate allergic reactions like hives or anaphylaxis — and compared them to 15 healthy children. Using DNA sequencing of bacterial genes from stool samples, the researchers found meaningful differences in the types and amounts of bacteria present between the two groups. Children with food allergy had more of certain bacteria like Bacteroides and Faecalibacterium, while healthy children had more bacteria associated with gut health, such as Bifidobacterium and Roseburia. Some bacteria, including Escherichia-Shigella, were found only in the allergy group.
The study also measured inflammatory markers in the stool — calprotectin (a marker of intestinal inflammation), eosinophil-derived neurotoxin or EDN (a marker of a type of immune cell activity linked to allergy), and IgA (an immune protein). When the researchers grouped patients by their inflammation levels, they found a specific pattern: children with the highest inflammation had a distinct bacterial profile, with more Veillonella bacteria and fewer beneficial Bifidobacterium-family bacteria. The amount of Veillonella in the gut was directly linked to higher levels of both calprotectin and EDN, suggesting this bacterium may play a role in driving gut inflammation in this condition.
This research suggests that non-IgE-mediated food allergy in children is not caused by a single, uniform disruption of gut bacteria, but rather involves different subtypes defined by distinct combinations of bacteria and inflammation markers. This is important because it may help explain why children with this condition can have varying symptoms and responses to treatment, and it points toward the potential use of stool-based microbiome and inflammatory testing as future diagnostic tools for a condition that currently has no reliable non-invasive tests.
Coșoreanu M, Gradisteanu Pircalabioru G, Lixandru-Petre I, Ionescu M, Ioan A, Cinteză E, et al.. (2026). Distinct Inflammation-Associated Microbiome Signatures in Pediatric Non-IgE-Mediated Food Allergy.. International journal of molecular sciences. https://doi.org/10.3390/ijms27167482