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. 2025 Feb;36(2):e70041.
doi: 10.1111/pai.70041.

The Janus face of Bifidobacterium in the development of atopic eczema: A role for compositional maturation

Martin Depner  1 , Diana Hazard Taft  2 , Stefanie Peschel  1 , Caroline Roduit  3   4   5 , Anne M Karvonen  6 , Cindy Barnig  7   8 , Amandine Divaret-Chauveau  9   10   11 , Josef Riedler  12 , Juha Pekkanen  6   13 , Elisabeth Schmausser-Hechfellner  1 , Giulia Pagani  1 , Roger Lauener  3   4   14   15 , Marjut Roponen  16 , Harald Renz  17   18 , Petra Ina Pfefferle  18   19 , Bianca Schaub  18   20 , Erika von Mutius  1   18   20 , Pirkka V Kirjavainen  6   21 , Markus J Ege  1   18   20 ; PASTURE study group
Collaborators, Affiliations

The Janus face of Bifidobacterium in the development of atopic eczema: A role for compositional maturation

Martin Depner et al. Pediatr Allergy Immunol. 2025 Feb.

Abstract

Background: Atopic eczema often develops in the first year of life, when the composition of the gut microbiota is most plastic as illustrated by the decrease in bifidobacteria after weaning. This may provide the opportunity for microbial stimuli and their environmental determinants to alter the disease course.

Objectives: To determine the role of the genus Bifidobacterium for atopic eczema in early childhood.

Methods: We analysed the bacterial composition in fecal samples of 618 children of the PASTURE ("Protection against Allergy-Study in Rural Environments") birth cohort using 16S rRNA amplicon sequencing of fecal samples collected at 2 and 12 months of age. Atopic eczema was defined as a parent-reported doctor's diagnosis until 2 years, and patterns of rash symptoms were classified by latent class analysis. We applied mediation models to assess direct and microbiota-mediated effects of environmental determinants on atopic eczema.

Results: The Bifidobacterium composition observed at 2 months was inversely related to atopic eczema (OR = 0.68 [0.53-0.87], p = .002) and persistent rash. This association was not seen at 12 months, when the composition of Bifidobacterium amplicon sequence variants (ASVs) was altered. The effect of beneficial ASVs at 2 months (OR = 0.72 [0.57-0.91]) was lost at 12 months (OR = 0.97 [0.76-1.24]), when distinct bifidobacteria tended to be positively related to late-onset rash.

Conclusions: The subgenus composition of Bifidobacterium undergoes substantial changes in the first year of life. The protective effect of Bifidobacterium depends on the ASV composition at the respective age of the infant, highlighting the importance of timing in prevention strategies targeting infant-microbe interactions.

Keywords: Bifidobacterium; atopic eczema; compositional maturation; late‐onset rash; persistent rash; subgenus composition; transient rash; window of opportunity.

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Conflict of interest statement

Amandine Divaret‐Chauveau reports grants from Don du Souffle, from Fondation du Souffle, from ARAIRLOR (Association Régionale d'Aide aux Insuffisants Respiratoires de Lorraine), from French public agency ASES, and from Novartis; received consulting fees from Sanofi, Stallergens, ALK and Aimmune Therpeutics; received honoraria for lectures and travel support for attending meetings from Novartis and ALK, and has stock options of Essilor Luxottica. Bianca Schaub reports consulting fees from GlaxoSmithKline, Novartis, ALK, Astra Zeneca and Sanofi. Markus Ege is an employee inventor of patents EP000002361632B1, EP000001964570B1, US000009950017B2. His employer has received investigational milk products from FrieslandCampina. EvM reports funding from the European Commission (LSH‐2004‐1.2.5‐1‐018996), the European Research Council (ERC‐2009‐AdG), Deutsche Forschungsgemeinschaft (Leibniz Price 2013), German Federal Ministry of Education and Research (German Center for Lung Research – DZL, Go Bio Initial Grant), Bavarian State Ministry of Health and Care for “URS Study”, OM Pharma S.A. (“Impact Chip Study”, “BEAR Study”); royalties from Elsevier GmbH, Georg Thieme Verlag, Springer‐Verlag GmbH, Elsevier Ltd., Springer Nature Group, Deutscher Apotheker Verlag, consulting fees from the Chinese University of Hongkong, European Commission, AstraZeneca, Imperial College London, OM Pharma S.A.; honoraria from ALK‐Abello Arzneimittel GmbH, Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI), Klinikum Rechts der Isar, University of Colorado, Paul‐Martini‐Stiftung, Astra Zeneca BioPharmaceuticals Medical, Imperial College London, Children’s Hospital Research Institute of Manitoba Kompetenzzentrum für Ernährung (Kern), OM Pharma S.A., Swedish Pediatric Society for Allergy and Lung Medicine, Chinese College of Allergy and Asthma (CCAA), Abbott Laboratories, Deutscher Apotheker Verlag GmbH & Co. KG, Socieded Chilena de Enfermedades Respiratorias, Japanese Society of Allergology, British Society for Asthma and Clinical Immunology, American Academy of Allergy, Asthma & Immunology, European Respiratory Society (ERS); support for attending meetings from Deutsches Zentrum für Lungenforschung (DZL), Fabio Luigi Massimo Ricciardolo/Contatto S.r.l., Fraunhofer ITEM Hannover, MCCA Institut für Immunologie Uni Wien, Karl‐Landsteiner Privatuniversität f. Gesundheitswissenschaften, Swiss Institute of Allergy and Asthma Research (SIAF) Davos (Associated Institute of the University of Zurich) MHH (Medizinische Hochschule Hannover), Natasha Allergy Research Foundation, Deutsche Forschungsgemeinschaft, Gordon Research Conferences, Socieded Chilena de Enfermedades Respiratorias, Arla, Universität Leiden, OM Pharma S.A., American Academy of Allergy, Asthma & Clinical Immunology, Deutsche Forschungsgemeinschaft (DFG), European Respiratory Society (ERS), Deutsche Gesellschaft für Kinder‐ und Jugendmedizin, World Allergy Organization (WAO), European Parliament, Gesellschaft für Pädiatrische Pneumologie (GPP), Helmholtz Association of German Research Centres, International Balzan Foundation "Prize". EvM has patent No. PCT/EP2019/085016 (Barn dust extract for the prevention and treatment of diseases) pending (Barn dust extract for the prevention and treatment of diseases) pending, royalties paid to ProtectImmun for patent EP2361632 (Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders, granted on 19 March 2014), and patents EP1411977 (Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases, granted on 18 April 2007), EP1637147 (Stable dust extract for allergy protection, granted on 10 December 2008), and EP 1964570 (Pharmaceutical compound to protect against allergies and inflammatory diseases, granted on 21 November 2012) licensed to ProtectImmun., Patent EP21189353.2. 2021. von Mutius E, Rankl B, Bracher F, Müller C, Walker A, Hauck SM, Merl‐Pham J, inventors; PROTEINS IDENTIFIED FROM BARN DUST EXTRACT FOR THE PREVENTION AND TREATMENT OF DISEASES, Patent PCT/US2021/016918. 2021. Martinez FD, Vercelli D, Snyder SA, von Mutius E, Pivniouk V, Marques dos Santos M, inventors; THERAPEUTIC FRACTIONS AND PROTEINS FROM ASTHMA‐PROTECTIVE FARM DUST, Patent EP21189353.2. 2021. von Mutius E, Rankl B, Bracher F, Müller C, Walker A, Hauck SM, Merl‐Pham J, Adler H, Yildirim A.Ö., Sattler M, Santos Dias Mourao A, Borggräfe J, O´Connor P.D., Plettenburg O, inventors; PROTEINS IDENTIFIED FROM BARN DUST EXTRACT FOR THE PREVENTION AND TREATMENT OF DISEASES. EvM has been serving as Member of the EXPANSE (funded by European Commission) Scientific Advisory Board, Member of the BEAMS External Scientific Advisory Board (ESAB), Member of the Editorial Board of “The Journal of Allergy and Clinical Immunology: In Practice”, Member of the Scientific Advisory Board of the Children’s Respiratory and Environmental Workgroup (CREW), Member of the International Scientific & Societal Advisory Board (ISSAB) of Utrecht Life Sciences (ULS) University of Utrecht, Member of External Review Panel of the Faculty of Veterinary Science, University of Utrecht, Member of the Selection Committee for the Gottfried Wilhelm Leibniz Programme (DFG), Member of the International Advisory Board of Asthma UK Centre for Applied Research (AUKCAR), Member of the International Advisory Board of “The Lancet Respiratory Medicine”, Member of the Scientific Advisory Board of the CHILD (Canadian Healthy Infant Longitudinal Development) study, McMaster University, Hamilton, Canada, Asthma UK Centre for Applied Research, Pediatric Scientific Advisory Board Iceland, Abbott Allergy Risk Reduction Advisory Board.

Figures

FIGURE 1
FIGURE 1
Composition of the gut microbiome at 2 and 12 months. Shown are the relative abundance values of the common (mean relative abundance ≥0.5%) genera at 2 or 12 months. “Rare” summarizes all taxa with a mean relative abundance below 0.5% at 2 or 12 months, respectively. N = 618. Lower and upper hinges of the boxes denote the first and third quartiles, respectively; the bold central line represents the median; the whiskers extend to the most extreme data point within a distance of 1.5 times the interquartile range from the hinges; extreme values lie beyond the whiskers and are marked by circles.
FIGURE 2
FIGURE 2
Bifidobacterium ASVs at 2 and 12 months. (A) Boxplot of the relative abundance of the most abundant (ASV01 to ASV07) and low abundant ASVs (summation variable, mean relative abundance <0.5%) within the genus Bifidobacterium only. Lower and upper hinges of the boxes denote the first and third quartiles, respectively; the bold central line represents the median; the whiskers extend to the most extreme data point within a distance of 1.5 times the interquartile range from the hinges; extreme values lie beyond the whiskers and are marked by circles. For description of ASVs see Table S2, N = 618. (B) Correlation of ASVs with TRFLP with respect to relative abundance. ASVs are named according Table S2. N = 618.
FIGURE 3
FIGURE 3
Atopic eczema and Bifidobacterium composition at 2 and 12 months. (A) Associations of atopic eczema and rash classes with primary Bifidobacterium axes at 2 (PA‐2) and 12 months (PA‐12). (B) Associations of atopic eczema (AE) with various Bifidobacterium ASVs and a summation score created from the relative abundance of the respective ASVs. For the description of ASVs see Table S1. N = 565.
FIGURE 4
FIGURE 4
Common PCA over both time points (joint PCA). (A, B) Shown are density plots (A) and scatter plots (B) of the first (two) axes of the joint PCAs on ASVs unrelated (left) or related (right) to the genus Bifidobacterium. N = 618. (C) Associations of atopic eczema and rash classes with the first axis of the joint Bifidobacterium PCA restricted to samples taken at month 2 (left) or 12 (right). N = 565.
FIGURE 5
FIGURE 5
PCA over both time points versus separate time points. Barplots showing the composition of relative abundance of ASV01 (red), ASV02 (light blue), ASV03 (dark blue), ASV04 (green), and other ASVs (gray) per sample. Samples are sorted by increasing values of the respective first PCA axis. In (A), the inverted first PCA axis of the joint PCA is shown. N = 618.
FIGURE 6
FIGURE 6
Mediation model showing the mediation by Bifidobacterium. Shown are beta estimates and p‐values for direct (blue) and indirect (green) effects with p < .1 in the mediation model. N = 565.
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