Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis

Abstract

Helicobacter pylori ( H. pylori ) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori -positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori -positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori , as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori , as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.

Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients

“…Summarizing the main findings, H. pylori infection in the upper gastrointestinal tract has been associated with an increased risk of developing PDAC [ 65 , 66 ]. H. pylori is believed to have an impact on carcinogenesis by promoting cell proliferation [ 67 ]. Significantly increased abundances of bacteria belonging to the phyla Bacteroidetes, Firmicutes [ 61 , 68 ], Proteobacteria, Actinobacteria, Fusobacteria, Verrucomicrobia [ 34 , 36 , 69 ], the genera Porphyromonas, Prevotella, Bifidobacterium [ 34 ] and Synergistetes, as well as the archaeal phylum Euryarchaeota [ 17 ], have been reported in PC in comparison to healthy controls.…”

Helicobacter pylori and its association with autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis and Sjögren syndrome

“…A link between H. pylori and autoimmune diseases such as immune thrombocytopenic purpura [ 18 ], IgA nephropathy [ 19 ], Devic disease [ 20 ], autoimmune pancreatitis [ 21 ], and autoimmune thyroid disease has been reported [ 22 ]. Moreover, H. pylori -related lymphomas of the gastrointestinal tract are associated with autoimmune diseases [ 23 ].…”

Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease

“…H. pylori infection is associated with several gastric pathologies, such as chronic gastritis, peptic and duodenal ulcers, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue [ 4 ]. Epidemiological studies correlate H. pylori infection with various extra gastrointestinal pathologies [ 5 , 6 ], such as ischemic heart disease [ 7 ], glaucoma [ 8 ], cerebrovascular diseases [ 9 ], autoimmune pancreatitis [ 10 ], and neurodegenerative diseases such as Alzheimer’s disease (AD) [ 11 , 12 ], mild cognitive impairment [ 13 ] and Parkinson’s disease [ 14 , 15 ]. Specifically, in the case of AD, the correlation is based on the high incidence of H. pylori in these patients [ 12 , 16 ], as well as by the presence of anti- H. pylori antibodies in their cerebrospinal fluid [ 11 , 17 ].…”