Clinical significance of a possible route of transmission of Candida and Helicobacter pylori associations in gastroduodenal pathology

Abstract

Fungal and bacterial interactions are widespread in the environment. Such intra-abdominal co-infections may lead to sepsis, potentially resulting in significant mortality. Interactions between invasive fungi (Candida) and pathogenic bacteria [Helicobacter pylori (H. pylori)] appear to be particularly relevant to human infection outcomes. Co-colonization by fungi and bacteria (coinfections) remains a pressing issue among patients with gastrointestinal pathology; however, the transmission routes and pathogenic mechanisms of these microbiome interactions are not yet fully understood. Candida species are known to support the growth of certain bacteria, and studies have observed a significant increase in the colony counts of these bacteria in the presence of fungi. As an opportunistic pathogen, Candida-in association with H. pylori-may contribute to dysbiosis of the oral microflora and other regions of the gastrointestinal tract, potentially facilitating disease progression. Therefore, understanding the interactions between fungi and bacteria is essential for improving early diagnosis and treatment efficacy. Synergistic effects have been identified in the development of resistance to antifungal and antibacterial therapies. Modern treatment strategies should consider focusing on methods to disrupt this synergy, as well as on preventative measures to limit the transmission of Candida-Helicobacter associations between individuals.

Key Words: Candida; Helicobacter pylori; Routes of transmission; Fungal and bacterial associations; Periodontitis; Vulvovaginal candidiasis; Microbiota

Core Tip: The phenomenon of fungal and bacterial associations is of significant interest for understanding gastric carcinogenesis. Representatives of the human microbiota can be etiological factors for various diseases. The most common are Helicobacter pylori (H. pylori) and Candida. The Candida-Helicobacter association is a poorly studied problem, although its significant role in the development of gastroduodenal pathology is not in doubt. Currently, there is insufficient understanding of the transmission pathways of H. pylori infection. Of great interest are polymicrobial extragastroduodenal foci of infections associated with H. pylori, in particular in the oral cavity, female birth canal, urinary tract. These issues require further investigation.

TO THE EDITOR

I read with great interest the review by Ramezani et al[1], which describes the research of a model for the vertical transmission of Helicobacter pylori (H. pylori) during infected with Candida harboring internalized H. pylori. I also welcome the opportunity to participate in the discussion regarding the potential vertical transmission of H. pylori encapsulated within Candida fungi[2].

I would like to offer my perspective regarding the various foci of H. pylori infection in the human body. The presence of H. pylori in the periodontal pockets of the human oral cavity has been reported in several studies. Specifically: First, H. pylori is associated with periodontal disease and may contribute to its pathogenesis; second, the H. pylori reservoir in periodontal pockets represents a potential source of gastric reinfection; third, periodontal inflammation may facilitate colonization by these bacteria; fourth, H. pylori within the oral microbiota may acquire resistance to anti-Helicobacter drugs; and fifth, the presence of H. pylori in the oral cavity may serve as an intra-organismal route of transmission, alongside transmission via the hands[3-6].

Notably, the updated Maastricht VI consensus does not explicitly address or offer practical recommendations regarding the impact of alternative H. pylori reservoirs or the potential vertical transmission from mother to newborn on the effectiveness of therapy and antibiotic resistance. The relevance of these aspects for the prevention of gastric cancer remains highly significant[7].

The phenomenon of fungal and bacterial associations is of considerable interest for understanding gastric carcinogenesis. Multipathogenic infections are common among patients, and polymicrobial diseases have been documented in numerous studies. These coinfections can vary in composition and may involve various representatives of the human microbiota, including viruses, bacteria, fungi, and parasites. Microorganisms other than H. pylori may influence the progression of gastric cancer and have been observed to penetrate the lamina propria of the gastric mucosa[8,9]. Furthermore, conditions such as bacterial vaginosis may act as reservoirs for pathogenic microflora that can metabolize antibiotics via specialized enzymes or utilize transport proteins to remove drugs, potentially reducing treatment efficacy[10]. Similarly, the periodontium serves as a reservoir for pathogenic microflora in the oral cavity, contributing to periodontal diseases. Certain periodontopathogenic microorganisms have demonstrated the ability to evade the human immune response using autophagic vesicles, thereby surviving within host cells[11]. Candida and bacteria localized within these foci appear to play a key role in the formation of microbial communities[12]. Bacterial and fungal persistence (dormancy) within the host may also contribute to the development of resistance to antibacterial and antifungal agents[13]. Another important mechanism for acquiring such resistance is horizontal gene transfer[14]. Additionally, the detection of H. pylori in duct stones and neoplasms of the salivary glands suggests a possible connection between this carcinogenic factor and specific glandular pathologies[15].

Deneha et al[16] confirmed that patients with early-stage periodontosis, as well as generalized periodontitis in later stages, exhibit numerous degenerative changes in the teeth and throughout the periodontal structure. In these patients, the authors found a correlation between degenerative changes in periodontal tissues and manifestations of intestinal dysbiosis. Guzeldemir and Toygar[17] highlighted the challenges in diagnosing and treating aggressive periodontitis associated with diffuse alveolar atrophy. It is often necessary to replace endosseous implants with custom-made subperiosteal implants due to weakening of the alveolar process. Subperiosteal implants are created using additive manufacturing. The need for subperiosteal implant technology is associated with the consequences of periodontal diseases. Subperiosteal implants, manufactured using 3D printing, represent a promising technology for patients with severe jawbone degeneration, provided long-term results are positive[18]. The clinical significance of the possible transmission of Candida and H. pylori infections in gastroduodenal pathology also lies in the fact that periodontal tissue damage, such as atrophic and resorbed maxilla and mandible, complicates the use of standard implantology. Despite the introduction of basal implantology, there are advantages and disadvantages. In these cases, effective rehabilitation is necessary[19]. The precise role of H. pylori in the development of aggressive periodontitis and maxillary or mandibular bone atrophy remains to be fully elucidated.

Similarly, research has suggested a link between the microbiome and the development of atrophic bacterial vaginitis[20]. While vulvovaginal candidiasis is reported in 70%-75% of women, it may complicate or be associated with the symptoms of atrophic vaginitis. Common routes of transmission of infections caused by Candida and H. pylori can spread to both gastrointestinal and vaginal pathologies, causing atrophic vaginitis, as well as abnormalities of the cervix or endometrium[21,22]. Other contributing factors include pathogenic aerobic intestinal microflora[23,24]. Villa et al[25] recommend further investigation into the role of anaerobic vaginal microflora, which frequently affects women of reproductive age. Finally, I would like to note that beyond the reservoirs mentioned here, other foci of H. pylori infection may exist. For example, Omura et al[26] have explored the presence of infection foci in the urinary tract involving Candida albicans, H. pylori, and Cytomegalovirus.

CONCLUSION

The phenomenon of H. pylori encapsulation in Candida should certainly be considered as evidence of the targeted creation of a substrate on the basis of which a specific function is programmed for study and use in the development of modern effective methods of treatment, primarily for gastric precancer and the prevention of gastric cancer.