Abstract
During a specific milk fermentation process with Bifidobacterium breve C50 and Streptococcus thermophilus 065 (LactofidusTM), postbiotics with possible immunomodulatory properties are produced. We investigated the effects of this fermentation product (FP) in vitro using a model that allows crosstalk between intestinal epithelial (IEC) and immune cells. IECs were exposed to FP and αCD3/CD28-activated peripheral blood mononuclear cells after which the mediator secretion was measured. Additionally, using a murine influenza vaccination model, immune development was assessed. Mice were fed an AIN93G diet containing FP or lactose as control. Vaccine-specific immunity was measured as delayed-type hypersensitivity (DTH) and correlated to intestinal and systemic immunomodulation levels. In vitro, exposure to FP enhanced IFNγ, TNFα and IL-17A concentrations. Moreover, IEC-derived galectin-3/galectin-9 and galectin-4/galectin-9 ratios were increased. In vivo, dietary intervention with FP increased vaccine-specific DTH responses as compared to the lactose-receiving group. Although no effects on humoral immunity and vaccine-specific T-cell responses were detected, an enhanced systemic serum galectin-3/galectin-9 and galectin-4/galectin-9 ratio correlated with a shift in RORγ (Th17) mRNA expression over regulatory TGFβ1 in the ileum. This was also positively correlated with the increased DTH response. These results indicate that FP can enhance epithelial galectin-3 and -4 over galectin-9 release, and boost adaptive immunity by promoting Th1- and Th17-type cytokines under inflammatory conditions in vitro. Similar variations in galectin and immune balance were observed in the vaccination model, where FP improved the influenza-specific DTH response.
Highlights
Licensee MDPI, Basel, Switzerland.The development of the mucosal immune system constitutes a crucial stage in early life and its development represents a decisive period for the establishment of a balanced mucosal immune and systemic immune function [1,2]
A model to study the crosstalk between IEC and innate as well as adaptive immune cells was used to investigate the immunomodulatory effects of fermentation products (FP)
Th17-type IL-17A concentrations were significantly upregulated upon exposure to 0.5% FP, as compared to medium (Figure 1C)
Summary
The development of the mucosal immune system constitutes a crucial stage in early life and its development represents a decisive period for the establishment of a balanced mucosal immune and systemic immune function [1,2]. Diet plays a pivotal role by providing all the necessary nutrients for growth and development of a healthy gut and supporting the establishment of a balanced microbiome and a proper maturation of the immune system. World Health Organization recommends exclusive breastfeeding during at least the first six months of life, which can be extended up to two years or beyond next to complementary food introduction [3]. Human milk is always the preferred option for infant nutrition, fermented milk-based infant formulas are being developed [4] and studied for their ability to modulate the immune function [5]
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