The Effects of Vitamins and Micronutrients on Helicobacter pylori Pathogenicity, Survival, and Eradication: A Crosstalk between Micronutrients and Immune System

Abstract

Helicobacter pylori as a class I carcinogen is correlated with a variety of severe gastroduodenal diseases; therefore, H. pylori eradication has become a priority to prevent gastric carcinogenesis. However, due to the emergence and spread of multidrug and single drug resistance mechanisms in H. pylori, as well as serious side effects of currently used antibiotic interventions, achieving successful H. pylori eradication has become exceedingly difficult. Recent studies expressed the intention of seeking novel strategies to improve H. pylori management and reduce the risk of H. pylori-associated intestinal and extragastrointestinal disorders. For which, vitamin supplementation has been demonstrated in many studies to have a tight interaction with H. pylori infection, either directly through the regulation of the host inflammatory pathways or indirectly by promoting the host immune response. On the other hand, H. pylori infection is reported to result in micronutrient malabsorption or deficiency. Furthermore, serum levels of particular micronutrients, especially vitamin D, are inversely correlated to the risk of H. pylori infection and eradication failure. Accordingly, vitamin supplementation might increase the efficiency of H. pylori eradication and reduce the risk of drug-related adverse effects. Therefore, this review aims at highlighting the regulatory role of micronutrients in H. pylori-induced host immune response and their potential capacity, as intrinsic antioxidants, for reducing oxidative stress and inflammation. We also discuss the uncovered mechanisms underlying the molecular and serological interactions between micronutrients and H. pylori infection to present a perspective for innovative in vitro investigations, as well as novel clinical implications.

Figure 1

The effect of micronutrients on H. pylori pathogenesis. (a) H. pylori can invade epithelial cells and interact with epidermal growth factor receptor (EGFR), toll-like receptor 4 (TLR4), and mitogen oxidase-1 (Mox1), thereby stimulating the activation of transcriptional factors and the production of reactive oxygen species (ROS). H. pylori neutrophil-activating protein (HP-NAP) and LPS lead to neutrophil activation and promotion of macrophage inflammatory responses, respectively. However, vitamin D and A interfere with CagA expression and ROS-mediated mitogen-activated protein kinase (MAPK) activation, respectively. Furthermore, vitamin D3 decomposition product (VDP1) lyses the bacterial cell and inhibits the colonization of H. pylori. Magnesium downregulates the activation of nuclear factor kappa B (NF-κB) and activated protein-1 (AP-1); therefore, suppressing the host inflammatory responses. (b) Neutrophil activation promotes the production of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), IL-1β, and ROS. Macrophage chemotactic protein-1 (MCP-1) stimulates the infiltration of macrophages and thereby increases the concentration of inducible nitric oxide synthase (iNOS), IL-1β, and ROS in the gut lamina propria. The infected epithelial cells overexpress proinflammatory cytokines such as cyclooxygenase-2 (COX-2), IL-8, and ROS. The overproduction of hepcidin in the liver, owing to H. pylori infection, interferes with the iron release from the macrophages. Vitamin D and A promote the expression of Vitamin D upregulated protein 1 (VDUP1) and immunoglobulin A (IgA), respectively. Regarding macrophages, vitamin D inhibits IL-8 secretion, increases β-defensin production through TLR activation and provokes the production of cathelicidin antimicrobial peptide (CAMP) by vitamin D receptor (VDR). Vitamin D regulates the reduced function of autolysosome and consequently stimulates H. pylori degradation in gastric epithelial cells. Moreover, this vitamin promotes the gut epithelial barrier by increasing the expression of tight junctions. On the other hand, vitamin C can reduce N-nitroso compound formation from nitric oxide (NO) and thereby inhibits carcinogenesis. (c) As chronic inflammation results in carcinogenesis, vitamin C promotes collagen production and prevents tumor metastasis. On the other hand, vitamin E reduces neutrophil adhesion and the secretion of prostaglandin E2 (PGE2) from tumor cells. Vitamin A and B6 induce B and T cell gut-homing, and selenium provokes the antibody secretion from B cells. Vitamin A is also involved in the production of transforming growth factor-beta (TGF-β) in the dendritic cells (DCs).