Human Milk Oligosaccharide 3′-GL Improves Influenza-Specific Vaccination Responsiveness and Immunity after Deoxynivalenol Exposure in Preclinical Models

Abstract

Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3′-galactosyl-lactose (3′-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet+ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3′-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3′-GL in TOS.

Specific Human Milk Oligosaccharides Differentially Promote Th1 and Regulatory Responses in a CpG-Activated Epithelial/Immune Cell Coculture

“…The relative high abundance of fucosylated and sialylated oligosaccharides in human milk especially is unique among mammals [37]. HMOS promote the intestinal barrier integrity and support innate and adaptive immune responses [30,[38][39][40]. Aside from on the immune system via the microbiome, HMOS have also been found to directly interact with immune cells [41].…”

Role of milk glycome in prevention, treatment, and recovery of COVID-19

“…Secondly, HMOs can bind the receptors on the epithelial cell surface to inhibit viral binding, which is critical for the prevention of viral infection initiation ( 107 ). Several HMO types including neutral, fucosylated, and sialylated shown to have antiviral effects on various viruses such as noroviruses ( 107 ), rotavirus ( 108 , 109 ), HIV ( 110 ), and influenza virus ( 111 , 112 ). Furthermore, the similarity between HMOs and receptor glycans enables them great decoys for viruses.…”

Dysbiosis of intestinal microbiota and metabolism caused by acute patulin exposure in mice

“…Short‐chain fatty acids (SCFAs), as the intestinal bacterial metabolites, are the primary energy source for enterocytes and play a vital role in intestinal barrier health. Deoxynivalenol and zearalenone have been shown to reduce intestinal SCFA levels in mice (Cai et al., 2022; Toutounchi et al., 2021). Similarly, we suspect that PAT may alter host and microbial metabolism.…”