310 - Unraveling Infant Allergy Risk: Solid Food Introduction Timing, Selection, and Gut Microbiome Axis

Publication Number: 2299.310

Vijay Shivnani, Plano West Senior High School, Plano, TX, United States; Patricia Milletich, University of Maryland Baltimore, Baltimore, MD, United States; Serena McCalla, iResearch Corporation, Glen Cove, NY, United States

Background: Allergic diseases are an increasing public health concern worldwide regarding complexity, severity, and incidence. The trend of food allergy (FA) pervasiveness is most pronounced in infant populations, who also face social and economic burdens. Despite the hypothesized role of diet in FA development, global infant food introduction guidelines do not account for food type or timing on allergy risk.

Objective: This study examined the infant gut microbiome as a modulating FA risk factor by 1) examining microbial composition in infants with vs. without allergies (0-24 months), 2) elucidating the role of food type and introduction on bacteria genera abundance, 3) associating food introduction timing with allergy risk, and 4) identifying enriched inflammatory pathways in infants with allergies (4-8 months).

Design/Methods: The DIABIMMUNE infant (N=198) cohort 16S rRNA stool sample data were used for analyses. Shannon and Simpson indices measured microbiome diversity. Linear Discriminant Analysis Effect Size and Paired Wilcoxon analyses identified allergy-associated metabolic pathways and bacteria genera, and modulation by food introduction. Cut point and odds ratio associated food introduction timing with allergy risk.

Results: Infants with allergies showed altered microbial compositions, albeit similar alpha diversity. Root vegetables and grains modulated 4 allergy-associated bacteria genera: Streptococcus (beetroot, rye, rice), Klebsiella (beetroot, barley, potato, rye), and Escherichia-Shigella (carrot). The influence of non-allergenic foods on the microbiome demonstrates potential for broader dietary intake to modulate FA. Food introduction causes the most significant genera abundance modulation at 4-8 months (p <.05; Beetroot-Klebsiella and Rye-Streptococcus) via 12 predicted overabundant pro-inflammatory pathways in infants with allergies, 7 of which degrade arenes. Given these pathways had increased functional abundance at the typical time of complementary feeding, it is plausible that increased potential for arene degradation in gut microbiomes stems from dietary intake. Within this 4-8 month age timeframe, 5 food products were associated with increased allergy risk (p <.05).

Conclusion(s): In the current paradigm, FA research would present universal infant diet suggestions. However, gut inter-individual variability indicates ineffectiveness of global guidelines at reducing allergy risks at an individual level. Therefore, this study proposes a prospective targeted risk reduction approach: fecal microbial sampling to create personalized feeding plans, reducing FA risk by optimizing the infant gut microbiome.

Fig. 1. Longitudinal Microbial Diversity, Composition, and Genera Abundance Differs Between Allergic and Non-Allergic Infants.
(A-B) Line graph displaying Shannon and Simpson indexes for alpha diversity. (C) Stacked bar plots indicate microbial composition (represented through 20 bacteria genera with the highest relative abundance) from samples at 6, 12, and 18 months of infant age. (D) LEfSe Analysis Identified Differentially Abundant Bacterial Genera. Bacteria genera associated with milk allergy at 6 months, but not at 12 or 18 months. Including the 20 genera with the highest relative abundance, genera with an LDA score>2 and a Wilcoxon p≤0.05 are presented.

Fig. 2. Food Introduction is Associated with Bacteria Relative Abundance and Allergy Risks Longitudinally.
(A) LEfSe analysis identified in differentially-abundant bacteria before and after food introduction. Root vegetables and grains caused abundance changes. (B-C) Bacteria abundance comparisons in 4-month Intervals are based on food introduction. Beetroot and rye at 4-8 months increased non-allergic bacteria and decreased allergic bacteria, respectively. Paired-Wilcoxon test determined significance. * = p≤0.05, ** = p≤0.01, *** = p≤0.001. (D) Association Between Solid Food Introduction Timing and FA Risk. A 4-8 month introduction increases milk allergy risk. Later introduction decreases FA risk. OR>1 indicates increased allergy risk when food is introduced prior to the cutpoint, whereas OR <1 indicates decreased risk.

Fig. 3. Inflammatory Pathways and Routes Upregulated in Allergic Infants.
LEfSE Analysis for Differential Abundance of Functional Pathways for (A) Egg allergies, (B) Milk allergies, and (C) Multiple Allergies. (D) Metabolic Routes as Related to Allergic Inflammation. Dietary compounds degraded via gut pathways at 4-8 months of age. MSH: Mycothiol. 3-PPA: 3-phenylpropanoate. PAA: Phenylacetate. PEA: Phenethylamine. 4-MC: 4-methylcatechol. 4-HPA: 4-hydroxyphenylacetate.