Abstract
Ulcerative colitis and Crohn’s disease, the two main forms of inflammatory bowel disease (IBD), are immunologically mediated disorders. Several therapies are focused on activated T cells as key targets. Although Lactobacillus kefiri has shown anti-inflammatory effects in animal models, few studies were done using human mucosal T cells. The aim of this work was to investigate the immunomodulatory effects of this bacterium on intestinal T cells from patients with active IBD. Mucosal biopsies and surgical samples from IBD adult patients (n = 19) or healthy donors (HC; n = 5) were used. Lamina propria mononuclear cells were isolated by enzymatic tissue digestion, and entero-adhesive Escherichia coli-specific lamina propria T cells (LPTC) were expanded. The immunomodulatory properties of L. kefiri CIDCA 8348 strain were evaluated on biopsies and on anti-CD3/CD28-activated LPTC. Secreted cytokines were quantified by ELISA, and cell proliferation and viability were assessed by flow cytometry. We found that L. kefiri reduced spontaneous release of IL-6 and IL-8 from inflamed biopsies ex vivo. Activated LPTC from IBD patients showed low proliferative rates and reduced secretion of TNF-α, IL-6, IFN-γ and IL-13 in the presence of L. kefiri. In addition, L. kefiri induced an increased frequency of CD4+FOXP3+ LPTC along with high levels of IL-10. This is the first report showing an immunomodulatory effect of L. kefiri CIDCA 8348 on human intestinal cells from IBD patients. Understanding the mechanisms of interaction between probiotics and immune mucosal cells may open new avenues for treatment and prevention of IBD.
Highlights
Inflammatory bowel disease (IBD) comprises a complex group of chronic relapsing diseases among which the most conspicuous are ulcerative colitis (UC) and Crohn’s disease (CD)
We studied the effect of the bacteria on biopsies from inflamed mucosa of IBD patients (n 13)
We aimed to evaluate the immunomodulatory properties of a probiotic Lactobacillus strain isolated from kefir on lamina propria CD4+ T cells from patients with active IBD
Summary
Inflammatory bowel disease (IBD) comprises a complex group of chronic relapsing diseases among which the most conspicuous are ulcerative colitis (UC) and Crohn’s disease (CD). Patients with IBD suffer chronic inflammation of the bowel mucosa that may affect the mucosal layer (UC) or the whole bowel wall (CD) (Torres et al, 2017; Ungaro et al, 2017). The etiology of these diseases is largely unknown, factors such as diet, certain genes related to the sensing of luminal microbes, secretion of antimicrobial peptides and autophagy have shown to be associated These findings, along with results obtained from animal models, including the fact that germ free mice do not develop experimental colitis, highlight the impact of the microbiota composition in the pathogenesis of these disorders (Onderdonk et al, 1977)
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