Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model

Abstract

In select Helicobacter pylori-infected populations with low gastric cancer, nematode coinfections are common and both helicobacter gastritis and filariasis are modeled in gerbils. We evaluated gastritis, worm counts, tissue cytokine gene expression levels and Th1/Th2-associated antibody responses in H. pylori and Brugia pahangi mono- and coinfected gerbils. H. pylori-associated gastritis indices were significantly lower 21 weeks post-infection in coinfected gerbils (p ≤ 0.05) and were inversely proportional to worm counts (r2 = −0.62, p < 0.003). Additionally, IFN-γ, IL-1β, CXCL1, IL-4 and IL-10 mRNA levels in the gastric antrum reflected a significant host response to gastric H. pylori and as well as systemic filariasis (p ≤ 0.05). Despite increasing worm burden (p < 0.05), gastritis progressed in coinfected gerbils (p < 0.03) becoming equivalent to H. pylori-infected gerbils at 42 weeks (p = 0.7). Pro- and anti-inflammatory mediator mRNA levels were notably downregulated in B. pahangi infected gerbils below uninfected control values, suggesting hyporesponsiveness to B. pahangi. Consistent with an increasing Th1 response to H. pylori, IgG2a (p < 0.01), IL-1β (p = 0.04) and CXCL1 (p = 0.006) responses significantly increased and IL-4 (p = 0.05) and IL-10 (p = 0.04) were decreased in coinfected gerbils at 42 weeks. Initial systemic responses to B. pahangi resulted in attenuated gastritis in coinfected gerbils, but subsequent filarid-associated hyporesponsiveness appears to have promoted H. pylori gastritis.

Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota

“…The odds ratio for developing GIN in mice infected with H. pylori alone was significantly elevated compared to mice co-infected with H. pylori and H. polygyrus. Consistent with prior data on helminth and Helicobacter co-infection in mice [11] and in gerbils [12], H. polygyrus co-infection did not reduce gastric inflammation. Thus, in three rodent models, helminthiasis reduced Helicobacter -associated gastric atrophy without reduction in gastric inflammation per se, supporting the hypothesis that H. pylori -associated premalignant gastric lesions are prevented, at least in part, by an alternative mechanism not directly related to severity of gastric inflammation.…”

“…Higher prevalence of helminth infections in H. pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma [9], with serologic evidence that life-long exposure through adulthood to a variety of parasites impacts inflammatory responses to H. pylori [10]. Experimental data from rodent models further support this hypothesis: gastric atrophy was reduced in H. felis and Heligmosomoides polygyrus co-infected C57BL/6 mice [11] and in H. pylori and Brugia pahangi co-infected gerbils [12]. …”

Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution

“…For example, Helicobacter hepaticus, which colonizes the intestine, has been shown to synergize with aflatoxin or hepatitis B virus to cause liver cancer in mice. In that model, b-catenin nuclear translocation was observed in tumors from animals exposed to both aflatoxin and H. hepaticus, but not in those treated with aflatoxin alone, thereby suggesting that both stimuli are involved in the cancer process (31). Other bacteria are also likely to influence cancer risk.…”

Serologic Evidence that Ascaris and Toxoplasma Infections Impact Inflammatory Responses to Helicobacter pylori in Colombians

“…Rodent models [10,11] and epidemiologic studies [18,50] support the hypothesis that concurrent helminth infection delays progression of Hp‐ induced premalignant lesions to gastric cancer. Our study demonstrates that Colombians living in Tumaco, and less so in Pasto/Tuquerres, are likely continually exposed to Hp , Al , Tg , and a broader spectrum of enteric pathogens including parasitic infections as previously detected by fecal testing [18].…”

“…This multifactorial etiology has been attributed to variations in Hp strain virulence [4] and origin [5], genetic polymorphisms of the human inflammatory response [6], environmental promoters such as smoking and dietary salt, environmental inhibitors including dietary antioxidants [7], and co‐colonization of Hp ‐infected atrophic stomachs with enteric flora [8,9]. Rodent models of helicobacter‐induced chronic gastritis have provided evidence that concurrent helminth infections reduce gastric atrophy [10,11], a key premalignant lesion. Therefore, parasites may also reduce the risk of Hp ‐associated gastric cancer in humans.…”