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Review
. 2023 Mar 31:14:1134785.
doi: 10.3389/fimmu.2023.1134785. eCollection 2023.

Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging

Catarina Lopes  1   2   3 , Tatiana C Almeida  1 , Pedro Pimentel-Nunes  4   5 , Mário Dinis-Ribeiro  1   6 , Carina Pereira  1   2
Affiliations
Review

Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging

Catarina Lopes et al. Front Immunol. .

Abstract

Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.

Keywords: atrophic gastritis; biomarkers; functional endoscopy; inflammation; microbiota.

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Conflict of interest statement

MD-R receives funding from Fujifilm through a scopes loan. The other authors declare the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The potential of functional endoscopy in gastric cancer early detection and management. In standard endoscopy (left side), after an upper gastrointestinal endoscopy, patients are stratified using OLGA and OLGIM classifications, which rank the severity and topography of atrophic and IM alterations in gastritis (13). However, endoscopy alone is associated with a non-negligible rate of missed conditions and a significant risk of metachronous lesions development (15, 16). On the right side, the promise of functional endoscopy by also integrating, for example, dysbiosis-driven inflammatory biomarkers derived from liquid biopsies, namely gastric juice, towards the individualization of care by targeting a reduction of missed lesions and personalization of patients’ management in gastric cancer early detection.
Figure 2
Figure 2
Dysbiosis-driven inflammation in gastric carcinogenesis. Once established in the gastric mucosa, H. pylori induces and maintains an inflammatory response, disrupting the epithelial barrier and altering the stomach acidity (27). In this altered environment, H. pylori colonization declines in the gastric carcinogenesis and other bacteria invade the gastric niche, culminating in dysbiosis (, , –65). Virulence factors of H. pylori activate NF-κB and COX-2 pathways, promoting interleukin (IL)-8 synthesis and other immune cells, which are heavily recruited in response to infection, leading to cytokine-induced changes in gastric physiology (–74). It also suppresses IL-2 synthesis, which is important for T-cell proliferation and survival (, –77).
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Grants and funding

This article is a result of the project NORTE-01-0145-FEDER-000050, supported by North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 partnership agreement, through the European Regional Development Fund (ERDF). TA is a research grant holder in the scope of that project. CL (UI/BD/151488/2021) and CP (SFRH/BPD/114803/2016) are research fellowship holders supported by Fundação para a Ciência e Tecnologia (FCT), co-financed by European Social Funds (ESF) and national funds of MCTES under the Human Strategic Reference Framework (POCH).