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Serum cytokine patterns are modulated in infants fed formula with probiotics or milk fat globule membranes: A randomized controlled trial
Department of Child Health Care, Childrens Hospital of Nanjing Medical University, Nanjing, China.
Department of Children Health Care, Childrens Hospital of Fudan University, Shanghai, China.
Department of Pediatrics, Beijing University Third Hospital, Bejing, China.
Arla Innovation Center, Arla Foods amba, Skejby, Denmark.
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2021 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, article id e0251293Article in journal (Refereed) Published
Abstract [en]

Background: Proteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants.

Objective: To compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants.

Design: FF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively.

Results: Compared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups.

Conclusions: Contrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.

Place, publisher, year, edition, pages
Public Library of Science , 2021. Vol. 16, article id e0251293
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Pediatrics
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URN: urn:nbn:se:umu:diva-183633DOI: 10.1371/journal.pone.0251293ISI: 000664628200057Scopus ID: 2-s2.0-85105820236OAI: oai:DiVA.org:umu-183633DiVA, id: diva2:1557870
Available from: 2021-05-27 Created: 2021-05-27 Last updated: 2023-09-05Bibliographically approved

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Lagerqvist, CarinaStenlund, HansHernell, OlleWest, Christina E.

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