Anti-Allergic Diarrhea Effect of Diosgenin Occurs via Improving Gut Dysbiosis in a Murine Model of Food Allergy.

Although the anti-allergic and prebiotic activities of diosgenin have been reported, the influence of diosgenin on intestinal immune and epithelial cells remains unclear. As the gut microbiota plays an important role in allergic disorders, this study aimed to investigate whether the anti-allergic diarrhea effect of diosgenin occurs via improving gut dysbiosis. In a murine food allergy model, the density of fecal bacterial growth on de Man, Rogossa and Sharpe (MRS) plates was diminished, and growth on reinforced clostridial medium (RCM) and lysogeny broth (LB) agar plates was elevated. However, the oral administration of diosgenin reduced the density of fecal bacteria and ameliorated diarrhea severity. Concordantly, reshaped diversity and an abundance of fecal microbes were observed in some of the diosgenin-treated mice, which showed a milder severity of diarrhea. The relevant fecal strains from the diosgenin-treated mice were defined and cultured with Caco-2 cells and allergen-primed mesenteric lymph node (MLN) cells. These strains exhibited protective effects against the cytokine/chemokine network and allergen-induced T-cell responses to varying degrees. By contrast, diosgenin limitedly regulated cytokine production and even reduced cell viability. Taken together, these findings show that diosgenin per se could not directly modulate the functionality of intestinal epithelial cells and immune cells, and its anti-allergic effect is most likely exerted via improving gut dysbiosis.

Relevant fecal microbes isolated from mice with food allergy elicited intestinal cytokine/chemokine network and T-cell immune responses.

The objective of this study was to identify the relevant fecal microbes from mice with food allergy and investigate the impact of these microbes on intestinal epithelial cells and allergen-specific T-cell responses. A murine model of ovalbumin (OVA)-induced food allergy was employed. The profile of fecal microbiota was evaluated by the traditional plating method and next-generation sequencing (NGS) of the 16S ribosomal RNA gene. The density of fecal bacteria growth on RCM, TSA and LB plates was elevated in mice with food allergy, whereas the diversity of fecal bacteria was decreased. Additionally, the relative abundances of Prevotellaceae and Prevotella were increased. The isolated fecal strains, mostly belonging to Enterococcus, Streptococcus and Vagococcus, significantly reduced the viability of intestinal Caco-2 cells but increased the production of interleukin (IL)-8, C-C motif chemokine ligand (CCL)-2, CCL-5, CCL-20 and C-X-C motif chemokine ligand (CXCL)-1. Moreover, cell expansion and secretion of IL-2, interferon (IFN)-γ, IL-4 and IL-17 by mesenteric lymph node (MLN) cells were augmented, whereas the production of IL-10 and transforming growth factor (TGF)-ß was diminished. Although individual fecal strains had varying degrees of impact on Caco-2 cells and MLN cells, these results precisely indicate a different profile of fecal microbiota between normal mice and allergic mice. Most important, the relevant fecal microbes involved in allergen-induced dysbiosis have the potential to induce intestinal cytokine/chemokine network and T-cell immune responses.