Formula supplementation with human and bovine milk oligosaccharides modulates blood IgG and T-helper cell populations, and ex vivo LPS-stimulated cytokine production in a neonatal preclinical model

Marcia H Monaco; Mei Wang; Jonas Hauser; Jian Yan; Ryan N Dilger; Sharon M Donovan

doi:10.3389/fimmu.2023.1327853

Formula supplementation with human and bovine milk oligosaccharides modulates blood IgG and T-helper cell populations, and ex vivo LPS-stimulated cytokine production in a neonatal preclinical model

Front Immunol. 2023 Dec 20:14:1327853. doi: 10.3389/fimmu.2023.1327853. eCollection 2023.

Authors

Marcia H Monaco¹, Mei Wang¹, Jonas Hauser², Jian Yan³, Ryan N Dilger⁴, Sharon M Donovan¹

Affiliations

¹ Department of Food Science and Human Nutrition, University of Illinois at Urbana Champaign, Urbana, IL, United States.
² Brain Health Department, Nestlé Institute of Health Sciences, Société des Produits Nestlé SA, Lausanne, Switzerland.
³ Nestlé Product Technology Center Nutrition, Vevey, Switzerland.
⁴ Department of Animal Sciences, University of Illinois at Urbana Champaign, Urbana, IL, United States.

Abstract

Introduction: Human milk contains structurally diverse oligosaccharides (HMO), which are multifunctional modulators of neonatal immune development. Our objective was to investigate formula supplemented with fucosylated (2'FL) + neutral (lacto-N-neotetraose, LNnt) oligosaccharides and/or sialylated bovine milk oligosaccharides (BMOS) on immunological outcomes.

Methods: Pigs (n=46) were randomized at 48h of age to four diets: sow milk replacer formula (CON), BMOS (CON + 6.5 g/L BMOS), HMO (CON + 1.0 g/L 2'FL + 0.5 g/L LNnT), or BMOS+HMO (CON + 6.5 g/L BMOS + 1.0 g/L 2'FL + 0.5 g/L LNnT). Blood and tissues were collected on postnatal day 33 for measurement of cytokines and IgG, phenotypic identification of immune cells, and ex vivo lipopolysaccharide (LPS)-stimulation of immune cells.

Results: Serum IgG was significantly lower in the HMO group than BMOS+HMO but did not differ from CON or BMOS. The percentage of PBMC T-helper cells was lower in BMOS+HMO than the other groups. Splenocytes from the BMOS group secreted more IL-1β when stimulated ex vivo with LPS compared to CON or HMO groups. For PBMCs, a statistical interaction of BMOS*HMO was observed for IL-10 secretion (p=0.037), with BMOS+HMO and HMO groups differing at p=0.1.

Discussion: The addition of a mix of fucosylated and sialylated oligosaccharides to infant formula provides specific activities in the immune system that differ from formulations supplemented with one oligosaccharide structure.

Keywords: 2'-fucosyllactose (2’FL); immunity; lacto-N-neotetraose (LNnT); milk oligosaccharides; pig.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines / analysis
Dietary Supplements
Female
Humans
Immunoglobulin G / analysis
Infant
Leukocytes, Mononuclear*
Lipopolysaccharides* / analysis
Milk, Human / chemistry
Oligosaccharides / chemistry
Oligosaccharides / pharmacology
Swine
T-Lymphocytes, Helper-Inducer

Substances

Lipopolysaccharides
Oligosaccharides
Cytokines
Immunoglobulin G

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Nestlé Nutrition R&D, Vevey, Switzerland.