Although we often talk about “gastritis” as if it were a single disease, it can actually arise from different causes and present acutely or persist for long periods of time. Some cases may be related to medications that irritate the gastric mucosa, autoimmune processes, exposure to certain substances, or alterations that affect the stomach’s protective barrier. However, one of the most important causes of chronic gastritis worldwide is infection with a bacterium called Helicobacter pylori (H. pylori).

To understand how gastritis develops, we must first remember that the stomach functions in a particularly harsh environment. To digest food, it produces acid and enzymes, but at the same time, it needs to protect its own cells from these substances. To do this, the inner surface of the stomach has a barrier made up of mucus, bicarbonate, and tightly connected epithelial cells. When this balance is disrupted, the mucosa can become more exposed to damage and trigger an inflammatory response. If the stimulus disappears, the inflammation may resolve; but if it persists for months or years, chronic gastritis may develop.

A recent analysis based on the Global Burden of Disease Study 2021 estimated that in 2021 there were approximately 38.3 million people with gastritis worldwide, compared with approximately 24.4 million in 1990.

However, these figures do not represent the number of people whose gastritis is caused by H. pylori. The infection can persist for years and maintain continuous inflammation in the mucosa, and in certain individuals, this prolonged exposure can contribute to progressive changes in the tissue. It is precisely this transition, from initially chronic inflammation to precancerous lesions, that is especially relevant for understanding gastric cancer.

Not all cases of chronic gastritis progress in the same way. One condition that requires special attention is chronic atrophic gastritis, in which prolonged inflammation is accompanied by a gradual loss of the stomach’s normal glands. The review published by Zhang and colleagues in Frontiers in Medicine in 2025 identifies two major forms of chronic atrophic gastritis: one associated with autoimmune processes and the other related to H. pylori infection. The latter is precisely the focus of the review because of its relationship with progression toward gastric cancer.

H. pylori has a characteristic that helps explain why it can cause long-term problems: it is capable of establishing itself in the stomach and remaining there for years. The bacterium continuously interacts with cells in the mucosa and with the immune system, generating an inflammatory response that attempts to control the infection but does not always succeed in eliminating it. The review describes how this persistent exposure can promote mucosal atrophy and intestinal metaplasia and, over time, contribute to progression toward gastric cancer.

This process becomes especially relevant when we consider the global burden of gastric cancer. According to GLOBOCAN 2022, approximately 968,784 new cases of stomach cancer and 660,175 deaths occurred worldwide, ranking it fifth in both cancer incidence and mortality.

Persistent inflammation can progressively modify the stomach environment; some glands may be lost, other cells may acquire different characteristics, and molecular alterations may accumulate.

And this is where one of the most important questions arises: how can such a common infection ultimately contribute to the development of cancer?

The answer involves much more than inflammation. H. pylori can interact with gastric cells, modify immune signals, promote oxidative stress, and alter mechanisms that regulate gene expression. The review by Zhang and colleagues analyzes precisely how these processes may connect chronic infection with atrophic gastritis and, eventually, gastric cancer.

To survive for long periods in the stomach, H. pylori uses different strategies that can affect cells in the gastric mucosa. Some strains produce substances, such as CagA and VacA, capable of altering mechanisms that normally help cells remain healthy and eliminate damaged components. As a result, stress within the cells may increase, and a greater release of inflammatory substances may occur. Over time, this can keep the stomach lining in a state of constant inflammation.

From gastritis to intestinal metaplasia

One of the best-known ways of explaining this progression is the so-called Correa cascade, a model that describes a possible sequence from an initially normal gastric mucosa to cancer. In simplified terms, it can be represented as: normal mucosa → chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → gastric cancer. The review uses precisely this model to show how different alterations can progressively accumulate.

One of the changes that may appear after years of inflammation is intestinal metaplasia. This occurs when the cells that normally line the stomach begin to change and acquire characteristics similar to those of intestinal cells. This change can occur in people with chronic gastritis associated with H. pylori and is considered a precancerous lesion.

However, having intestinal metaplasia does not mean having cancer, nor does it necessarily mean that cancer will develop. It means that the stomach tissue has undergone significant changes and that, depending on each case, medical monitoring and follow-up may be necessary.

If inflammation continues for a long time, cells may continue to accumulate changes. In some people, these changes can progress to a stage called dysplasia, in which the cells begin to look and behave more abnormally. Dysplasia can be classified as low-grade or high-grade and represents a more advanced step within the process that, in certain cases, can lead to gastric cancer.

The problem is not only in the DNA

For a long time, talking about cancer meant thinking primarily about mutations. Today, we know that the story is more complex, since there are modifications capable of changing the way certain genes function without necessarily altering the DNA sequence. In simplified terms, it is comparable to having the same instruction book but changing which pages are read and which remain closed.

Persistent H. pylori infection can contribute to modifying these regulatory mechanisms and affect genes related to the cell cycle, tumor-suppressor pathways such as p53, and signals associated with tumor development, including the WNT pathway.

The immune system attempts to control H. pylori, in many cases without success. This creates a particular situation: the body’s defenses continue to respond while the bacterium remains present. This prolonged interaction can gradually modify the stomach microenvironment, stimulate inflammation, progressively damage tissues, and also exhaust the immune response.

The review also examines a particularly interesting mechanism: cellular senescence. When a cell accumulates certain types of damage, it may stop dividing and enter a state known as senescence. In principle, this can function as a protective mechanism because it prevents a damaged cell from continuing to proliferate. However, senescent cells do not necessarily remain inactive.

If these cells accumulate, the signals they produce can contribute to maintaining inflammation and modifying the tissue around them, which could promote conditions related to tumor growth and progression.

Having gastritis does not mean that you will develop gastric cancer. However, if symptoms are frequent or persist over time, it is important not to ignore them and to consult a healthcare professional to determine their cause.

One aspect that can be evaluated is the presence of Helicobacter pylori. When this infection is confirmed, a doctor may prescribe treatment to eliminate the bacterium and subsequently verify whether eradication was successful. This is especially important because treating H. pylori early, before significant changes appear in the stomach lining, can help reduce the risk of progression.

In people who already have atrophic gastritis, intestinal metaplasia, or other alterations of the mucosa, a doctor may recommend periodic checkups and, in some cases, follow-up with endoscopy. The frequency of these evaluations will depend on the changes identified and each patient’s level of risk.

For this reason, persistent gastritis should not simply become something a person learns to live with. Understanding what is causing it, identifying whether an H. pylori infection is present, and treating it when appropriate can help protect stomach health over the long term.

Gastritis does not mean cancer, but it can be an opportunity to pay attention to gastric health. Seeking medical care in a timely manner, treating the underlying causes, and maintaining the recommended follow-up can make it possible to act before certain changes have the opportunity to progress.