Helicobacter pylori infection and association with chronic diseases: A focus on cardiovascular disease, MASLD, and type 2 diabetes

Abstract

Helicobacter pylori (H. pylori) infection is a globally prevalent gastrointestinal pathogen increasingly linked to various extra-gastric non-communicable diseases (NCDs). This review addresses the guiding question: What epidemiological and mechanistic links explain the association between H. pylori infection and chronic conditions such as cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes mellitus (T2DM)? The manuscript synthesizes evidence from epidemiological studies and mechanistic research. In CVD, H. pylori exacerbates chronic vascular inflammation, endothelial dysfunction, and autoimmune-like responses such as molecular mimicry. In MASLD, H. pylori induces insulin resistance (IR), hepatic inflammation, and microbiota-mediated liver injury, although findings remain inconclusive across populations. For T2DM, multiple pathways including NLRP3 inflammasome activation, hormonal imbalances (e.g., ghrelin, leptin), and immune-genetic interactions involving TLR4 and SOCS3 suggest a role for H. pylori in metabolic dysregulation and impaired glycemic control. While researchers have not yet fully elucidated causality, these findings indicate H. pylori as a potential modifiable risk factor for NCDs. Future longitudinal and interventional studies are warranted to determine whether eradication of H. pylori can mitigate chronic disease.

Keywords: Cardiovascular disease; Diabetes mellitus; Helicobacter pylori; Metabolic dysfunction-associated steatotic liver disease.

Fig. 1

The relationship between Helicobacter pylori and chronic diseases, including cardiovascular diseases, non-alcoholic fatty liver disease, and diabetes. Legend: Proposed mechanisms linking Helicobacter pylori (H. pylori) infection to chronic metabolic diseases including cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes mellitus (T2DM). H. pylori infection may contribute to the pathogenesis of chronic diseases through multiple pathways, including immune modulation (e.g., increased IgA/IgG2, TNF-α), systemic inflammation (elevated IL-6, IL-1β, CRP), oxidative stress, and dysregulation of lipid and glucose metabolism. In the heart, H. pylori is associated with atherosclerosis, thrombosis, and altered lipid profiles, promoting CVD and coronary heart disease (CHD). In the liver, chronic inflammation and abnormal signaling pathways (e.g., IKK/NF-κB, JNK) contribute to insulin resistance (IR) and MASLD. In the pancreas, LPS-mediated pathways activate MAPK and EGFR signaling, leading to apoptosis, metabolic disturbances, and enhanced risk of T2DM.