AUTHOR=Hose Alexander J. , Pagani Giulia , Karvonen Anne M. , Kirjavainen Pirkka V. , Roduit Caroline , Genuneit Jon , Schmaußer-Hechfellner Elisabeth , Depner Martin , Frei Remo , Lauener Roger , Riedler Josef , Schaub Bianca , Fuchs Oliver , von Mutius Erika , Divaret-Chauveau Amandine , Pekkanen Juha , Ege Markus J. 

TITLE=Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.651709

DOI=10.3389/fimmu.2021.651709

ISSN=1664-3224

ABSTRACT=Diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systemati-cally assess feeding patterns and to relate them to asthma risk at school age.
PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were re-ported by parents in monthly diaries between the 3rd and 12th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing.
Data on feeding practice with at least one reported time point was available in 1042 of the 1133 re-cruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an ele-vated risk of asthma at age 6 as compared to the other classes (odds ratio = 8.47 [2.52–28.56], p=0.001) and was characterized by daily meat consumption and rare consumption of milk and yo-ghurt, which we termed unbalanced meat consumption (UMC). A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of UMC in PASTURE and independently in LUKAS2. The effect of UMC was particularly strong for non-atopic asthma and asthma irrespective-ly of early bronchitis (odds ratio = 17.0 [5.2–56.1], p<0.001). UMC fostered growth of iron scaveng-ing bacteria such as Acinetobacter (1.28 [1.00-1.63), which was also related to asthma (OR=1.55 [1.18-2.03]). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (OR=1.58 [1.13-2.19], p=0.007.
By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards over-growth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation.