SELECTIVELY IMPROVEMENT OF THE RESPONSE OF IMMUNE CELLS TO OPPORTUNISTIC MICROORGANISMS: AN INNOVATIVE PROPOSAL FOR IBD FROM AN ANCIENT GRAIN

Abstract

Abstract BACKGROUND Inflammatory Bowel Disease (IBD) results from an unbalanced immune response to the gut microbiome. There is a lack of proposals that integrate and may balance the multiple factors (Immunity, microbiome and diet) that together condition the onset and evolution of the disease. D-fagomine is a small molecule, naturally present in buckwheat grain. It Is a monosaccharide mimetic showing glycosidase enzyme inhibition properties. Clinical studies have shown its efficacy to control postprandial glycemic response. Subsequent research “in vitro” had also shown D-fagomine to inhibit the fimbriae adhesion and biofilm formation of some proteobacteria, including ie E. coli or Salmonella. ORIGINAL AIM The aim of the study was to confirm the effects of D-fagomine on the adhesion to human gut mucosa using adherent-invasive E coli (AIEC) that is a microorganism usually linked to IBD. METHOD Ex vivo human resected colonic mucosa was cultured (4 h) with AIEC inoculum and D-fagomine at different range of doses (0-5000 ppm). The amount of E. coli in tissue and supernatant was quantified, measuring also TNF-alfa and LDH. RESULTS It was confirmed the inhibition of AIEC adhesion to the colonic mucosa in a direct dose-response relationship. Totally unexpected, D-fagomine was found to modulate TNF-alfa in an apparent double sigmoid curve with the max activity in the range of 50 ppm (Figure 1). This curve corresponds to an activator of the innate immune cells with mechanism related to complement activation, (ie mannose, betaglucan). Finally D-fagomine was helping the mucosa to detect and overcome the evasion mechanism of AIEC at the range of 50 ppm. Additional studies were considered necessary to confirm these results with different models. ADDED AIM The novel aim was to assess the human immune cell response (other than colonic mucosa) in the dose range of 50 ppm D-fagomine in front of different microorganisms able to evade the human immune system. ADDED METHOD Ex vivo human blood was cultured with D-fagomine (50 ppm) and the correspondent inoculum of different models: bacteria = E. coli (AIEC) and fungus = Blastomyces sp. TNF-alfa was quantified. ADDED RESULTS D-fagomine, at 50 ppm, stimulates TNF-alfa response of human immune cells against AIEC and also Blastomyces (Figure 2). Both models give coherent results, and confirm that D-fagomine at the range of 50 ppm improves the capacity of the innate immune cells to detect human opportunistic microorganisms. CONCLUSIONS Our results have shown for the first time D-fagomine helping human immune cells to develop a more efficient immune response to better control the presence of opportunistic microorganisms. This is of great interest in IBD and also synergic with D-fagomine activity of delaying the release of sugars from diet to the gut, reducing then the negative effects of a Western Diet to humans and also to its microbiome.