P715 Selective enhancement of immune cell response to opportunistic microorganisms: An innovative proposal for Inflammatory Bowel Disease from an ancient grain.
Pumarola Segura, S.(1);
(1)Pumarola Innovation, Innovation, Barcelona, Spain;
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 that together condition the onset and evolution of the disease: immunity, microbiome and diet.
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.
The original 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.
A) 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.
B) Ex vivo human blood was cultured with D-fagomine (50 ppm) and the correspondent inoculum of different microorganism models able to evade the human immune system: bacteria = E. coli (AIEC) and fungus = Blastomyces sp. TNF-alfa was quantified.
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 (Fig 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 (method B) were carried out with the result that D-fagomine, at 50 ppm, stimulates TNF-alfa response of human immune cells against AIEC and also Blastomyces (Fig 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.
Fig 1 Fig2
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 is also synergistic with the other known properties of D-fagomine, which overall could finally help reduce some of the negative effects of the Western diet on humans and also their microbiome.