Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients

Abstract

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings?cagA+ H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients.Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains) in CD is unclear.Objective: To assess the relationship between gastric Hp infection (cagA+ strains) and duodenal histological damage in patients with CD.Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed.Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30–40%), but cagA+ strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA+ Hp+ compared to cagA- Hp+ (p < 0.01) and Hp- (p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD (p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA+ Hp+ compared to Hp- and was significantly downregulated in cagA+ potential-CD subjects compared to other groups.Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA+ strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA+ Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage.

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…By affecting immune and inflammatory responses [ 78 , 92 , 431 , 432 , 433 ]. HPI may protect against asthma and allergy (particularly in children), autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis [RA] and multiple sclerosis, coeliac disease), inflammatory bowel disease (especially Crohn’s disease), eosinophilic esophagitis, eczema, obesity [ 9 , 78 , 342 , 433 , 434 , 435 , 436 , 437 , 438 , 439 , 440 , 441 ] and tooth loss [ 442 ]. Negative associations between these diseases and HPI (beneficial effects) were observed mainly in patients colonized with cagA+ strains of H.p.…”

Effects of Helicobacter Pylori Infection on Serology and Intestinal Mucosal Changes in Pediatric Patients With Celiac Disease: A Retrospective Cohort Study

“…Helicobacter pylori settles in the antrum mucosa of the stomach and reproduces. It may cause pathological mucosal changes (such as ulcer, intraepithelial lymphocytosis, and villous atrophy) in the gastric and duodenum by increasing gastric acid secretion, activating both the Th1/Th17 and T-reg pathways [5][6]. We anticipate that this intestinal mucosal damage (such as intraepithelial lymphocytosis and villous atrophy) caused by Helicobacter pylori may confuse the diagnosis of celiac disease.…”

Analysis of gastric and duodenal biopsy results in patients presenting with dyspepsia: a cross-sectional study in a middle eastern population

“…In the literature, a study done by Lebwohl et al found that H. pylori infection was lower in CD positive patients than in those without CD 17. Many other studies found similar H. pylori infection rates among individuals with and without CD, with one showing the presence of variations in CD’s histological damage depending on the H. pylori strain 18 29. No difference between gender and between ages was found in the literature 17–25 27–30…”