https://orcid.org/0000-0001-9475-6965
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ABSTRACT
Human Milk Oligosaccharides (HMOs) have been proposed to be instrumental in building immune competence. To explore the role of HMOs in allergy prevention, twenty-one HMOs were quantified in breast milk samples and associated with sensitisation in infants. 2′-fucosyllactose (2′-FL) levels were positively associated with an increased risk of sensitisation, atopic dermatitis and recurrent skin rash. Interestingly, 2′-FL levels, ranging from 1.35 to 1.95 g/L, were associated with a higher prevalence of non-allergic and non-sensitised infants. The role of 2′-FL and lacto-N-neotetraose (LNnT) was further investigated in allergic sensitisation models in vivo. Oral administration of HMOs decreased allergic sensitisation. This was associated with gut microbiota and short-chain fatty acid (SCFA) production changes. Aligned with the clinical associations, the decreased sensitisation was not observed with lower and higher tested doses of the HMOs supporting a U-shape association between 2′-FL and LNnT levels and allergic sensitisation risk reduction in humans and mice.
Trial registration: ClinicalTrials.gov identifier: NCT02550236.
Acknowledgements
The authors would like to thank Eline van der Beek and Giles Major for their critical review of the manuscript. Authors’ Contribution: Sébastien Holvoet, Cheong Kwong Chung, Tristan Bourdeau, and Dominique Donnicola designed and performed the in vivo, ex vivo, and in vitro experiments, analysed the results, drafted the manuscript and the figures, reviewed and agreed with the manuscript. Francis Foata and Severine Combremont performed the microbiota analysis, analysed the data, drafted the figures for the manuscript, reviewed and agreed with the final manuscript; Ellen Ní Cléirigh and Maya Shevlyakova analysed the human data and generated the statistical reports linking HMO and infant health outcomes, drafted the manuscript, reviewed and agreed with the final manuscript; Gregory Lefevre, and Aristea Binia analysed the data on variant analysis, drafted the manuscript, reviewed and agreed with the final manuscript; Chiara Nembrini, Mandy Vogel, and Wieland Kiess designed and managed the human clinical data acquisition and HMO quantification, designed the analytical plan, drafted the manuscript, reviewed and agreed with the final manuscript; Norbert Sprenger, Mario Noti, and Sophie Nutten advised on scientific strategy, provided resources, reviewed and agreed with the manuscript; Carine Blanchard ideated the work, designed experiments, analysed the statistical reports, drafted the manuscript, reviewed and agreed with the final manuscript and serves as the corresponding author.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Ethics statement
The samples analysed in this study have been collected from a sub-cohort of the German LIFE Child study (Michel et al., Citation2020; Poulain et al., Citation2017). To participate in the study, written informed consent was obtained from breast milk donors; for samples and/or medical information from infants, consent was obtained from their parents or legal guardians. The German LIFE Child study was designed in accordance with the Declaration of Helsinki and under the supervision of the Ethics Committee of the University of Leipzig, Germany, which also approved the study (Reg. No. 264-10-19042010). The LIFE Child study is registered on ClinicalTrials.gov under the clinical trial number: NCT02550236. The animal study protocols were approved by the “Service Vétérinaire du Canton de Vaud”, Switzerland under the authorisation VD2382.
Data availability statement
The statistical plan and reports of the human clinical data as well as the protocol, statistical plan and statistical report of the animal studies are available upon request.