The Combination of 2'-Fucosyllactose with Short-Chain Galacto-Oligosaccharides and Long-Chain Fructo-Oligosaccharides that Enhance Influenza Vaccine Responses Is Associated with Mucosal Immune Regulation in Mice.

Abstract

BACKGROUND:

A critical role for host-microbe interactions and establishment of vaccine responses has been postulated. Human milk oligosaccharides, of which 2'-fucosyllactose (2'FL) is the most prevalent, are known to alter host-associated microbial communities and play a critical role in the immunologic development of breastfed infants.

OBJECTIVES:

Dietary supplementation with a combination of 2'FL and prebiotic short-chain (sc) galacto-oligosaccharides (GOS) and long-chain (lc) fructo-oligosaccharides (FOS) was employed to examine human milk oligosaccharide effects on immune responsiveness, within a murine influenza vaccination model.

METHODS:

Female mice (6 wk old, C57Bl/6JOlaHsd) were fed either control diet (CON) or scGOS/lcFOS/2'FL-containing diet (GF2F) for 45 d. After starting dietary intervention (day 14), mice received a primary influenza vaccination (day 0) followed by a booster vaccination (day 21), after which ear challenges were conducted to measure vaccine-specific delayed type hypersensitivity (DTH). Serum immunoglobulin (Ig) levels, fecal and cecal microbial community structure, short-chain fatty acids, host intestinal gene expression and cellular responses in the mesenteric lymph nodes (MLNs) were also measured.

RESULTS:

Relative to CON, mice fed the GF2F diet had increased influenza vaccine-specific DTH responses (79.3%; P < 0.01), higher levels of both IgG1 (3.2-fold; P < 0.05) and IgG2a (1.2-fold; P < 0.05) in serum, and greater percentages of activated B cells (0.3%; P < 0.05), regulatory T cells (1.64%; P < 0.05), and T-helper 1 cells (2.2%; P < 0.05) in their MLNs. GF2F-fed mice had elevated cecal butyric (P < 0.05) and propionic (P < 0.05) acid levels relative to CON, which correlated to DTH responses (R2 = 0.22; P = 0.05 and R2 = 0.39; P < 0.01, respectively). Specific fecal microbial taxa altered in GF2F diet fed mice relative to CON were significantly correlated with the DTH response and IgG2a level increases.

CONCLUSIONS:

Dietary GF2F improved influenza vaccine-specific T-helper 1 responses and B cell activation in MLNs and enhanced systemic IgG1 and IgG2a concentrations in mice. These immunologic changes are correlated with microbial community structure and metabolites.

• Authors: Ling Xiao, Phillip A Engen, Thea Leusink-Muis, Ingrid van Ark, Bernd Stahl, Saskia A Overbeek, Johan Garssen, Ankur Naqib, Stefan J Green, Ali Keshavarzian, Gert Folkerts, Belinda Van't Land
• Journal: The Journal of nutrition (J Nutr) Vol. 149 Issue 5 Pg. 856-869 (05 01 2019) ISSN: 1541-6100 [Electronic] United States
• PMID: 31050747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © American Society for Nutrition 2019.

Chemical References

• Immunoglobulin G
• Immunologic Factors
• Influenza Vaccines
• Oligosaccharides
• Prebiotics
• Trisaccharides
• Fructose
• Galactose
• 2'-fucosyllactose

Topics

• Animals
• B-Lymphocytes
• Cecum (metabolism, microbiology)
• Colon (metabolism, microbiology)
• Feces (microbiology)
• Female
• Fructose (pharmacology, therapeutic use)
• Galactose (pharmacology, therapeutic use)
• Humans
• Immunoglobulin G (blood)
• Immunologic Factors (pharmacology, therapeutic use)
• Influenza Vaccines
• Influenza, Human (immunology, prevention & control)
• Mice, Inbred C57BL
• Milk, Human (chemistry)
• Mucous Membrane (drug effects, immunology)
• Oligosaccharides (pharmacology, therapeutic use)
• Prebiotics
• Th1 Cells
• Trisaccharides (pharmacology, therapeutic use)
• Vaccination