Background/Objectives: Helicobacter pylori (H. pylori) is a well-established pathogen associated with chronic gastritis and gastric malignancies. Recent studies suggest that members of the Streptococcus anginosus group (SAG), particularly S. anginosus and S. constellatus, may also contribute to gastric mucosal damage, especially when co-infecting with H. pylori. This study aimed to evaluate the prevalence of these three bacterial species and their associations with gastric lesions in Vietnamese patients. Methods: A cross-sectional study was conducted on 200 adult patients with gastritis diagnosed by endoscopy and biopsy. PCR analysed gastric tissue samples from the antrum and corpus for H. pylori, S. anginosus, and S. constellatus. Gastric lesions were classified histologically, and associations with bacterial infections were assessed using odds ratios (OR) and 95% confidence intervals. Results: Infection rates were 62.5% for H. pylori, 62% for S. constellatus, and 48.5% for S. anginosus. Coinfections were frequent, with 25% of patients infected by all three bacteria. Atrophic gastritis was the most common lesion (80%) and was significantly associated with all three bacteria, particularly H. pylori (OR = 7.7), and in co-infections (e.g., H. pylori + S. constellatus, OR = 7.4, p < 0.0001). Triple infection was strongly linked to both atrophy (OR = 5.1) and intestinal metaplasia/ dysplasia (OR = 3.4, p = 0.007). Conclusions: Polymicrobial infections involving H. pylori and SAG bacteria are common in Vietnamese patients with gastritis and are significantly associated with more severe gastric lesions. These findings highlight the need for broader microbial screening and integrated management strategies to improve gastritis treatment and gastric cancer prevention in high-prevalence settings.
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