Helicobacter pylori infection: Beyond gastric manifestations

Table 1 Non-gastric manifestations of Helicobacter pylori and their suggested mechanisms of pathophysiology

Non-gastric manifestation	Mechanisms of pathology suggested to be correlated
Allergic diseases	Hygiene hypothesis[9,96]
Alzheimer’s disease	Vitamin B12 deficiency leading to increased concentrations of homocysteine[109]
	Anormal hyperphosphorylation of the TAU protein caused by H. pylori infection[109]
	ApoE polymorphism[110]
Asthma	Treg pattern, suppressing Th-2-mediated allergic response[94]
Atherosclerosis and myocardial infarction	Stimulation of foam production inside macrophages, contributing to the magnification of the atherosclerotic plaque and arterial dysfunction[122]
B12 deficiency	Still to be clarified, but proven to be independent of gastric atrophy and bleeding that impair their dietary absorption[49]
Cholelithiasis	Presence of H. pylori infected bile[43,44]
Coronary arterial disease/systemic arterial stiffness	Increased levels of homocysteine[132].
Gastroesophageal reflux disease	Hyperacidity[25]
Diabetes mellitus	Increased cytokine production; phosphorylation of serine residues from the insulin receptor substrate[136]
Hepatic carcinoma	Inflammatory, fibrotic and, consequently, necrotic process[37,38]
Idiopathic thrombocytopenic purpura (ITP)	CagA may stimulate the synthesis of anti-CagA antibodies that cross-react with platelet surface antigens causing ITP[74,75]
Inflammatory bowel disease	Reduced intestinal inflammation through release of IL-18 and development of FoxP3-positive regulatory T cells[16-18]
	Neutrophil-activating protein reducing inflammation through Toll-like receptor 2 and IL-10 stimulation[19,20]
Iron deficiency anemia	Still to be clarified, but proven to be independent of gastric atrophy and bleeding that impair their dietary absorption[49]
	Relationship with growth disorders in children[52,53]
Multiple sclerosis	Hygiene hypothesis[9]
	Inhibitory induction of H. pylori over the Th1 and Th17 immune response[103]
Non-alcoholic fatty liver disease	H. pylori induced insulin resistance[32]
	Reduced production of adiponectin[33]
	Liver inflammation[34,35]
Ophthalmic manifestations	Systemic inflammatory status; increased oxidative stress; mitochondrial dysfunction; damage to DNA[82]
Parkinson’s disease	Increased synthesis of 1-methyl-4-phenyl-1,2,36-tetrahydropyridine[118]
	Reduced levodopa absorption[118]

H. pylori: Helicobacter pylori; CagA: Cytotoxin-associated gene A.