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Helicobacter pylori (H. pylori) infection, which affects approximately half of the world’s population, remains a serious public health problem. As H. pylori infection leads to a number of gastric pathologies, including inflammation, gastroduodenal ulcers, and malignancies, early detection and treatment are crucial to preventing the spread of the infection. Multiple extragastric complications, such as iron deficiency anaemia, immune thrombocytopenic purpura, vitamin B12 deficiency, diabetes mellitus, cardiovascular diseases, and certain neurological disorders, have also been linked to H. pylori infection. An awareness of H. pylori and associated health hazards is necessary to minimize or even eradicate the infection. Therefore, there is an urgent need to raise the standards for the currently employed diagnostic, eradication, alternative treatment strategies. In addition, a brief overview of traditional and cutting-edge approaches that have proven effective in identifying and managing H. pylori is needed. Based on the test and laboratory equipment available and patient clinical characteristics, the optimal diagnostic approach requires weighing several factors. The pathophysiology and pathogenic mechanisms of H. pylori should also be studied, focusing more on the infection-causing virulence factors of this bacterium. Accordingly, this review aims to demonstrate the various diagnostic, pathophysiological, therapeutic, and eradication tactics available for H. pylori, emphasizing both their advantages and disadvantages. Invasive methods (such as quick urease testing, biopsy, or culture) or noninvasive methods (such as breath tests, stool investigations, or serological tests) can be used. We also present the most recent worldwide recommendations along with scientific evidence for treating H. pylori. In addition to the current antibiotic regimens, alternative therapies may also be considered. It is imperative to eradicate the infections caused by H. pylori as soon as possible to prevent problems and the development of stomach cancer. In conclusion, significant advances have been made in identifying and treating H. pylori. To improve eradication rates, peptide mass fingerprinting can be used as a diagnostic tool, and vaccines can also eliminate the infection.
Keywords: Helicobacter pylori, history, pathogenesis, diagnosis, therapy, preventionIt was first observed in the late nineteenth century that Helicobacter pylori (H. pylori), a highly mobile gram-negative, distinctively twisted bacterium, was present in the gastrointestinal system [1,2]. The researchers who demonstrated that H. pylori can cause gastritis received the Nobel Prize in 2005 due to the wide-ranging implications of their discovery [2]. Because the stomach was assumed to be a sterile organ where bacteria could not grow due to the low pH, the bacteria were presumed to have been orally ingested rather than being gastric inhabitants. H. pylori, however, has been linked with several digestive illnesses manifesting as indigestion since it was first discovered in the early 1980s by Warren and Marshall [3,4,5].
H. pylori is typically associated with chronic active gastroenteritis, and the bacteria lives in the glands beneath the mucosal surface [6]. There is a significant relationship between H. pylori infection and stomach cancer, peptic ulcer illness, and gastric mucosal lymphoid tissue lymphoma [3,5]. A study conducted by Shatila and Thomas [7] indicated that H. pylori infection can result in stomach carcinoma and mucosa-associated lymphoid tissue lymphoma in 90% of cases. Furthermore, H. pylori infection is closely related to stomach ulcers (up to 80% of cases) and duodenal ulcers (in approximately 90% of cases). There is also a close relationship between H. pylori infection and duodenal ulcers (present in 80% of cases), stomach ulcers (up to 80% of cases), and carcinomas [8]. As part of its 2014 recommendations, the World Health Organization (WHO) urged the eradication of H. pylori to reduce stomach cancer fatalities worldwide. Among the potential hazards to public health and the environment are bacterial strains of H. pylori that are clarithromycin-resistant [9].
Approximately half of the worldwide population is colonized by H. pylori, and the colonized population is incredibly widespread [10,11]. There is no clear way to explain how this bacterium is spread, but oral or faecal exposure leading to person-to-person transfer is thought to be the dominant method [11]. H. pylori is more commonly found in Asia, Latin America, and Africa than in North America and Oceania, where it may be found in only 24% of the population [12,13]. Among H. pylori-infected individuals, 34.7% live in industrialized nations, while 50.8% live in resource-poor nations [14], and most contemporary studies indicate that H. pylori infection incidence has been steadily decreasing. Despite this pattern, there has been an alarming increase in antibiotic-resistant strains of H. pylori [15]. Children are usually asymptomatic transmitters of infections who later develop signs as adults. However, it is true that the vast majority of infected people do not actually exhibit symptoms of H. pylori infection [16]. During outbreaks, the number of people affected by H. pylori infection varies between 85 and 95% in poor nations and between 30 and 50% in industrialized nations [17,18,19]. Unfortunately, the exact method by which H. pylori is transmitted is unknown. There are, however, reports that it is distributed through the faecal–oral and/or oral-to-oral routes. Drinking water and food tainted with this pathogen are associated with this form of spreading [11,16]. Infections are more likely to occur as a result of poor hygiene, insufficient nutrition, and geographical variances [20], whereas the development of some virulent factors allows H. pylori to persist at a lower pH level. Since the bacterium cannot produce acid itself, the urease enzyme neutralizes gastric acid [20].
Since H. pylori is linked to a number of gastric diseases, such as gastroenteritis, gastroduodenal ulcers, and even stomach carcinoma, it is critical to diagnose and treat infection with this pathogen early and effectively to prevent it from spreading [21]. H. pylori infection diagnostic tests are classified into two broad categories: invasive procedures (gastric biopsy, endoscopy-mediated) and noninvasive procedures (liquid biopsy). Nonendoscopic tests include the antigen detection test and the urea breath test for identifying vigorous H. pylori infections [22]. It is also possible to test for urease in stomach samples obtained during endoscopy, with a sensitivity and specificity of approximately 90% and 95%, respectively [23]. H. pylori infections are diagnosed histopathologically with 95% and 98% sensitivity and specificity, respectively. Antigen stool tests represent the most economical diagnostic approach currently available in areas with low-to-moderate H. pylori prevalence. Despite their high specificity and low sensitivity, prompt monoclonal immunochromatographic antigen stool tests are limited in their utility [24]. It is often possible to obtain fast results from PCR stool tests from commercial sources [25]. Serology-based diagnostics are ineffective in identifying current H. pylori infections because H. pylori antibodies linger even after the infection has been eradicated [4]. The recognition of active infections with H. pylori by endoscopy, along with noninvasive diagnostic tests (e.g., urea breath and antigen stool tests), may be less sensitive if bismuth or antimicrobials are taken within one to two weeks of the test.
It is still unclear and controversial what role this pathogen plays in stomach disorders. H. pylori causes passive inflammation inside the gastric epithelium and alters signal transduction pathways that serve as a platform for pathogenesis, but it also develops antimicrobial resistance via genetic changes and biofilm development [26,27]. It is also important to note that strain variation plays a role in the virulence of H. pylori, in addition to a number of other factors. The development of specific virulence genes facilitates the interaction between bacteria and hosts [28]. In a previous study conducted by Palamides et al. [29], different isolates of H. pylori had different pathogenicity and were associated with different prognoses. Despite the difficulty of removing H. pylori, it has been somewhat successful to date. It is crucial to identify the virulence and pathogenic pathways of H. pylori to develop effective methods to combat H. pylori infection [19,30]. From these virulence mechanisms, therapeutic approaches may be derived. For new medications and vaccines to be developed, it is therefore important to recognize exactly how virulence factors affect H. pylori pathogenicity. Throughout this article, we discuss the characteristics and clinical features of H. pylori infection, and we provide a brief summary of conventional and cutting-edge identification techniques that are effective for identifying and treating infections with this pathogen. A review of the vaccination strategies for and pathogenicity of H. pylori is also included.
It is estimated that H. pylori left Africa approximately 60,000 years ago within an infected individual [31]. Previously, H. pylori had been found in contemporary animals before people migrated out of Africa and was eventually found in humans [32]. As early as 1982, doctors Barry Marshall and Robin Warren of Perth, Western Australia, discovered H. pylori in patients suffering from inflammation and ulcers in their gastric mucosa. A widespread belief at the time was that germs cannot survive in the acidic environment of the stomach. As a result of Marshall and Warren’s discovery, Physiology’s Nobel Prize was awarded to them in 2005. Marshall and Warren’s study was the first to find spiral-shaped bacteria in the stomach wall; however, German researchers were not able to cultivate them, so their findings were ignored [33]. According to some modest studies conducted in the early twentieth century, most people suffering from gastric ulcers and gastric cancer had bent rods in their stomachs. It is noteworthy that an American investigation of 1180 gastric samples reported in 1954 did not find the bacteria. This led to a decline in enthusiasm for research on these bacteria [34].
Since the 1970s, when bacteria in the guts of stomach ulcer patients were visualized, curiosity about bacterial roles in gut illness has been renewed [35]. Likewise, Robin Warren and Barry Marshall had seen the bacteria in 1979, and they studied it together beginning in 1981. They saw colonies only after accidentally leaving petri dishes incubating for five days during the Easter weekend in 1982, after numerous failed attempts to cultivate stomach bacteria. Unlike earlier researchers, Warren and Marshall maintained that the majority of gastritis cases and peptic ulcers are caused by bacterial infections rather than stress or salty foods [36]. It was initially believed that gastritis and ulcers were not related, but after several years, numerous teams of scholars confirmed this link [37]. To demonstrate that H. pylori was the cause of his gastritis and not simply a by-product, Marshall swallowed some cultured H. pylori. He began feeling ill with nausea and vomiting a few days later. He underwent endoscopy 10 days after inoculation, which showed signs of gastritis and H. pylori in his stomach. As a result of these findings, H. pylori was determined to be the causal agent.
According to Marshall and Warren, many cases of gastritis can be successfully treated with antimicrobials. In 1994, the National Institutes of Health (NIH) suggested including antimicrobials in the treatment protocol for gastric and duodenal ulcers caused by H. pylori [38]. Many papers have been published since 1997 detailing the pathophysiology, immunology, and pathogenicity of H. pylori. Depending on the region, H. pylori infection varies, with developing countries bearing the heaviest burden [39]. Several external factors, including food, carcinogen exposure, excessive alcohol consumption, and tobacco, can contribute to H. pylori development. H. pylori infections after invasion can also be influenced by the persistence of the bacteria as well as their pathogenicity [40,41].
H. pylori infection is classified in three stages: the colonization of the stomach mucosa, the consequent immune response, and disease development. Figure 1 illustrates several virulence factors of H. pylori that contribute to its pathogenicity and effects on host cells. The bacterium floats in the direction of the epithelial membrane when it enters the stomach, taking advantage of areas of the stomach wall that are injured [42,43]. It uses Tlp receptors, mainly TlpB, to regulate flagellar motion based on chemical messengers in the cell environment [44]. Reactive oxygen species, as well as urea, gastric acid, lactate, and gastric acid, serve as signals for these receptors; urea is a key factor in microbial invasion [44]. There are also unknown molecules that may play a role in this mechanism [45]. H. pylori uses urease to defend itself against the acidic medium around it. Urea is converted into ammonia and other beneficial compounds by urease, which raises the pH of the microenvironment while protecting the bacterium from the acid in the stomach. In the presence of this barrier, the mucosal gel lining the stomach wall becomes less viscous, allowing the bacteria to travel through the mucus towards the gastric pits in which they will eventually colonize [45,46].