Helicobacter pylori in Inflammatory Bowel Diseases: Active Protagonist or Innocent Bystander?

Abstract

Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to the pathogenesis of autoimmune diseases. While the specific etiopathogenesis of inflammatory bowel diseases (IBDs) is still unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. Various bacterial and viral pathogens have been implicated in the pathogenesis of IBDs. Numerous studies suggest a correlation between H. pylori infection and IBDs. While subject to debate, this link suggests that the bacterium's presence somehow impacts the progression of IBDs by modifying the diversity of the gut microbiota, consequently altering local chemical profiles and disrupting the pattern of gut immune response. However, epidemiological evidence indicates a protective role of H. pylori infection against the onset of autoimmune diseases. Additionally, laboratory findings demonstrate H. pylori's capacity to promote immune tolerance and restrict inflammatory reactions. The aim of this review is to elucidate the proposed mechanisms and confounding factors that underlie the potential association between H. pylori infection and IBDs.

Keywords: Crohn’s disease; H. pylori; IBD; diagnosis; eradication; immunological modulation; inflammatory bowel disease; molecular biology; ulcerative colitis.

Figure 1

Molecular mechanisms underlying the protective role of H. pylori against IBDs. H. pylori induces the modulation of T helper 17/Treg immunological response by inducing a shift from M1 to M2 macrophage lineage which reduces levels of interleukin IL-17F and IL-21, suppresses TLR mediated signaling pathways, and increases the expression of IL-13, IL-10, and CD163, leading to anti-inflammatory effects. H. pylori: Helicobacter pylori; IL: interleukin; TLR: Toll-like receptor; Treg: regulatory T; M: macrophage.

Figure 2

Role of the NLRP3 inflammasome in protection against inflammatory bowel diseases. Pathogen-associated molecular patterns from H. pylori trigger NLRP3 inflammasome activation, which upregulates caspase-1 expression, thereby leading to the activation of interleukin IL-18 and IL-1β cytokines. IL-1β as a potent pro-inflammatory agent and IL-18 by controlling responses mediated by TCD4+ cells promote extragastric immunomodulation by suppressing the Th-17 response in the cecum and increasing IL-10 in the mesenteric lymph nodes. H. pylori: Helicobacter pylori; IL: interleukin; NLRP3: NLR family pyrin domain containing 3.