Abstract
Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel diseases (IBD). In this work, we studied how Lactobacillus and Bifidobacterium strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6–CCL20 and IL-23/Th17 axes in Crohn’s disease (CD) and ulcerative colitis (UC) patients. All Lactobacillus and Bifidobacterium strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6–CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only B. breve Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-α and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients.
Highlights
The two major types of inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis (UC)
As several probiotic strains can inhibit adherent-invasive E. coli (AIEC) invasion of intestinal epithelial cells (IECs) [41,42], we first assessed whether the Lactobacillus (L1 —Lactobacillus acidophilus LA1, L2 —Lactobacillus paracasei 101/37) or Bifidobacterium
Our results suggest that probiotic strains can efficiently reduce the number of AIEC-LF82 that reach sub-epithelial regions, affecting the invasion and survival of LF82 within intestinal epithelial cells and strongly attenuate the secretion of IL-8, but not of CCL20, an important chemokine involved in the recruitment of DCs, Th17 and Th1/17 cells to the gut mucosa [43,44]
Summary
The two major types of inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis (UC) The former is characterized by chronic inflammation involving most commonly the distal part of the small intestine, ileum and colon, while the latter is characterized by a more. IBD pathogenesis is a complex process, mainly linked to uncontrolled mucosal inflammation in genetically predisposed individuals, due to an abnormal immune response against luminal antigens and microbiota [2,3,4]. This overly inflammatory response can be triggered by a breakdown in the intestinal homeostasis among the microbiota and resident innate and adaptive immune cells [5,6]. Even if IBD appear to differ in their inflammatory mechanisms, with CD having been classically linked to Th1 and Th17 cells, while
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