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Model representing the role of H. pylori and other factors in gastric carcinogenesis, based on the cascade proposed by Correa et al. (96).
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Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointes...
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... of gastric MALT lymphoma (490). Because of the diagnostic controver- sies and the relative rarity of this disorder, the exact incidence in H. pylori -positive subjects is unknown, but MALT lymphomas occur in fewer than 1% of H. pylori -positive subjects (491). Randomized trials for the effect of H. pylori eradication in MALT lymphoma patients are therefore not feasible, but various case series reported that eradication can lead to complete remission in patients with stage IE MALT lymphoma confined to the stomach (120, 186, 451, 698). Overall, approximately 60 to 80% of these patients reach complete remission following H. pylori eradication, some 10% continue to have signs of minimal residual disease, and the remainder show no response or disease progression. The variation in response between different series may in part have been due to different criteria for the diagnosis of MALT lymphoma, potentially including some patients with benign lymphoid aggregates. Ten to 35% of those who initially reach complete remission after H. pylori eradication show recurrent disease during further follow-up. For that reason, long-term follow-up of MALT lymphoma patients is mandatory (518). A major predictor for response appears to be the presence of a t(11;18) (q21;q21) translocation. This translocation is associated with API2-MALT1 fusion, the former being involved in regulation of apoptosis, the latter resembling a caspase-like protein, but with as-yet-unknown biological function. Together, the fusion leads to suppression of apoptosis. Several studies have reported that MALT lymphomas with this translocation do not at all or only rarely respond to H. pylori eradication (287, 371). GERD. GERD has long been considered to occur indepen- dently of H. pylori colonization, i.e., to occur with the same frequency and severity in H. pylori -positive and H. pylori -negative subjects. This opinion was based on cross-sectional observations which suggested that the prevalence of H. pylori among GERD patients was similar to that among controls (689). However, further studies suggested that H. pylori might protect against the development of GERD and as such also be of benefit to their hosts. This slowly emerging concept came from repeated observations of a low prevalence of H. pylori among GERD patients, particularly of more virulent strains (174); opposing time and geographical trends for H. pylori prevalence compared with the incidence of GERD and its complications; a potentially increased incidence of GERD after H. pylori eradication (347); and the recognition that H. pylori -induced corpus gastritis reduced acid secretion. The hypothesis was that H. pylori -induced inflammation of the gastric corpus had an acid-suppressive effect, thus preventing patients from contracting GERD. For individual subjects, these insights so far have limited relevance other than that they underline the concept that eradication therapy should be prescribed only when there is a clear indication for H. pylori diagnosis and treatment. There is, with further data having become available, no evidence that H. pylori eradication has a considerable impact on either the new development of GERD (641), the worsening of preexisting GERD when treatment has been withdrawn during disease remission (552), or preexistent GERD in remission during PPI maintenance therapy (335, 548). Together, these data show that although epidemiologic data suggest that there may be an inverse relation between H. pylori and GERD, the risk for new development or worsening of preexistent GERD is not an issue in the decision of whether or not to treat H. pylori . Extragastroduodenal disorders. H. pylori has been linked to a variety of extragastric disorders. These include coronary heart disease, dermatological disorders such as rosacea and idiopathic urticaria, autoimmune thyroid disease and thrombocytopenic purpura, iron deficiency anemia, Raynaud’s phenomenon, scleroderma, migraine, and Guillain-Barr ́ syn- drome. The underlying hypothetical mechanisms include chronic low-grade activation of the coagulation cascade, accel- erating atherosclerosis, and antigenic mimicry between H. pylori and host epitopes leading to autoimmune disorders (214). This has led to large numbers of case studies of patients with these disorders. Several groups in particular have studied patients with idiopathic thrombocytopenic purpura and showed that when these patients are colonized with H. pylori , eradication therapy has a significant effect over placebo for improvement of thrombocyte counts (215, 291, 612). H. pylori testing and treatment should be considered for these patients. In patients with the other conditions mentioned above, there is as yet no role for H. pylori eradication, and further adequate, randomized trials are needed (37, 343, 358). Infection with H. pylori results in a typical sequence of events, ultimately resulting in the development of gastric diseases. The sequence depicted in Fig. 5 was first suggested by Correa et al. (96) and has since been supported by many other studies. Colonization of the gastric mucosa by H. pylori first results in the induction of an inflammatory response, predominantly of the Th1 type. The initial acute gastritis is followed by active chronic gastritis, which lasts for life if the infection is not treated (340). Nevertheless, H. pylori -positive subjects are mostly unaware of this inflammation due to the lack of clinical symptoms. This inflammatory response is characterized by an influx of neutrophils, mononuclear cells, and T-helper 1 (Th1) cells, typically aimed at clearing intracellular infections (see “Im- mune Response,” below). However, H. pylori is not an intracellular pathogen, and thus the Th1 response results in epithelial cell damage rather than in the removal of H. pylori . The ongoing presence of H. pylori thus causes a lifelong proinflammatory response coupled to cellular damage and initiates the histological cascade depicted in Fig. 5. The continuous production of reactive oxygen species that results from the ongoing inflammation can give rise to DNA damage, thus inducing the multiple mutations thought to be required for initiation of the cancer cascade (Fig. 5). Various tests have been developed for the detection of H. pylori , each with their specific advantages and disadvantages (Table 2). The available tests are generally divided into invasive tests, based on gastric specimens for histology, culture, or other methods, and noninvasive tests, based on peripheral samples, such as blood, breath samples, stools, urine, or saliva for detection of antibodies, bacterial antigens, or urease activity. The choice of a specific test for an individual patient depends on local experience and the clinical setting (for reviews, see references 372, 640, and 713). In research protocols, a combination of two methods is often applied. In daily clinical practice, use of a single test is generally adequate, and most tests are sufficiently accurate to be used for this purpose. For routine diagnostic purposes, histology, urea breath testing, and culture are currently most often used, whereas the use of serology is most appropriate for large epidemiological studies (Table 2). In hospital-based care, many patients undergo endoscopy, which is then combined with an invasive test for H. pylori . Otherwise, breath tests and serology are commonly used. For children, fecal antigen tests offer the opportunity to assess H. pylori status without the need for endoscopy or vena puncture (Table 2). Although H. pylori is sensitive to a wide range of antibiotics in vitro, they all fail as monotherapy in vivo. In infected patients, the most effective single drug is clarithromycin, which leads to an approximate eradication rate of 40% when given twice daily for 10 to 14 days (237, 409, 504). The lack of efficacy of monotherapy is related to the niche of H. pylori , residing at lower pH in a viscous mucus layer. Dual therapies, combining twice-daily-dosed PPI with, in particular, amoxicillin, are still in use in some countries, but dual therapies have mostly been replaced by triple therapies. These combine two antibiotics with either a bismuth compound or a PPI. A further alternative is provided by quadruple therapies, which combine the bismuth compound and PPI with two antibiotics. The exact mode of action of bismuth compounds is unknown, but H. pylori is susceptible to these compounds both in vivo and in vitro (23, 349, 667). Tetracycline, amoxicillin, imidazoles (predominantly metronidazole and tinidazole), and a few selected macrolides (in particular clarithromycin, sometimes azithromycin) are probably the drugs most widely used for H. pylori eradication therapy (412). Recently, the use of rifabutin (502, 503) and furazolidone (152, 173, 245, 699) has been promoted. However, as their effectiveness is limited and many patients do not tolerate furazolidone, the primary use of these two antibiotics is a second-line rescue therapy of patients harboring metroni- dazole-resistant isolates (227, 410, 486). Occasionally the use of ciprofloxacin and related fluoroquinolones (131, 192) and other antibiotics, such as rifampin and streptomycin (544), has been reported, but these drugs seem to have no serious advantages over the aforementioned ones. The use of these drugs has resulted in effective therapies against H. pylori , with consistent eradication rates over 80%. Various treatment dura- tions, doses, and drug combinations have been studied, but none have consistently reached eradication levels in excess of 90 to 95%. Failures are in particular related to insufficient therapy adherence, often because of side effects, and to the presence of antimicrobial resistance. Such resistance is common in patients who have had previous antibiotic treatment, including failed eradication therapies (408). In the past decade, much effort has been devoted to the development of alternative ...
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... reach complete remission after H. pylori eradication show recurrent disease during further follow-up. For that reason, long-term follow-up of MALT lymphoma patients is mandatory (518). A major predictor for response appears to be the presence of a t(11;18) (q21;q21) translocation. This translocation is associated with API2-MALT1 fusion, the former being involved in regulation of apoptosis, the latter resembling a caspase-like protein, but with as-yet-unknown biological function. Together, the fusion leads to suppression of apoptosis. Several studies have reported that MALT lymphomas with this translocation do not at all or only rarely respond to H. pylori eradication (287, 371). GERD. GERD has long been considered to occur indepen- dently of H. pylori colonization, i.e., to occur with the same frequency and severity in H. pylori -positive and H. pylori -negative subjects. This opinion was based on cross-sectional observations which suggested that the prevalence of H. pylori among GERD patients was similar to that among controls (689). However, further studies suggested that H. pylori might protect against the development of GERD and as such also be of benefit to their hosts. This slowly emerging concept came from repeated observations of a low prevalence of H. pylori among GERD patients, particularly of more virulent strains (174); opposing time and geographical trends for H. pylori prevalence compared with the incidence of GERD and its complications; a potentially increased incidence of GERD after H. pylori eradication (347); and the recognition that H. pylori -induced corpus gastritis reduced acid secretion. The hypothesis was that H. pylori -induced inflammation of the gastric corpus had an acid-suppressive effect, thus preventing patients from contracting GERD. For individual subjects, these insights so far have limited relevance other than that they underline the concept that eradication therapy should be prescribed only when there is a clear indication for H. pylori diagnosis and treatment. There is, with further data having become available, no evidence that H. pylori eradication has a considerable impact on either the new development of GERD (641), the worsening of preexisting GERD when treatment has been withdrawn during disease remission (552), or preexistent GERD in remission during PPI maintenance therapy (335, 548). Together, these data show that although epidemiologic data suggest that there may be an inverse relation between H. pylori and GERD, the risk for new development or worsening of preexistent GERD is not an issue in the decision of whether or not to treat H. pylori . Extragastroduodenal disorders. H. pylori has been linked to a variety of extragastric disorders. These include coronary heart disease, dermatological disorders such as rosacea and idiopathic urticaria, autoimmune thyroid disease and thrombocytopenic purpura, iron deficiency anemia, Raynaud’s phenomenon, scleroderma, migraine, and Guillain-Barr ́ syn- drome. The underlying hypothetical mechanisms include chronic low-grade activation of the coagulation cascade, accel- erating atherosclerosis, and antigenic mimicry between H. pylori and host epitopes leading to autoimmune disorders (214). This has led to large numbers of case studies of patients with these disorders. Several groups in particular have studied patients with idiopathic thrombocytopenic purpura and showed that when these patients are colonized with H. pylori , eradication therapy has a significant effect over placebo for improvement of thrombocyte counts (215, 291, 612). H. pylori testing and treatment should be considered for these patients. In patients with the other conditions mentioned above, there is as yet no role for H. pylori eradication, and further adequate, randomized trials are needed (37, 343, 358). Infection with H. pylori results in a typical sequence of events, ultimately resulting in the development of gastric diseases. The sequence depicted in Fig. 5 was first suggested by Correa et al. (96) and has since been supported by many other studies. Colonization of the gastric mucosa by H. pylori first results in the induction of an inflammatory response, predominantly of the Th1 type. The initial acute gastritis is followed by active chronic gastritis, which lasts for life if the infection is not treated (340). Nevertheless, H. pylori -positive subjects are mostly unaware of this inflammation due to the lack of clinical symptoms. This inflammatory response is characterized by an influx of neutrophils, mononuclear cells, and T-helper 1 (Th1) cells, typically aimed at clearing intracellular infections (see “Im- mune Response,” below). However, H. pylori is not an intracellular pathogen, and thus the Th1 response results in epithelial cell damage rather than in the removal of H. pylori . The ongoing presence of H. pylori thus causes a lifelong proinflammatory response coupled to cellular damage and initiates the histological cascade depicted in Fig. 5. The continuous production of reactive oxygen species that results from the ongoing inflammation can give rise to DNA damage, thus inducing the multiple mutations thought to be required for initiation of the cancer cascade (Fig. 5). Various tests have been developed for the detection of H. pylori , each with their specific advantages and disadvantages (Table 2). The available tests are generally divided into invasive tests, based on gastric specimens for histology, culture, or other methods, and noninvasive tests, based on peripheral samples, such as blood, breath samples, stools, urine, or saliva for detection of antibodies, bacterial antigens, or urease activity. The choice of a specific test for an individual patient depends on local experience and the clinical setting (for reviews, see references 372, 640, and 713). In research protocols, a combination of two methods is often applied. In daily clinical practice, use of a single test is generally adequate, and most tests are sufficiently accurate to be used for this purpose. For routine diagnostic purposes, histology, urea breath testing, and culture are currently most often used, whereas the use of serology is most appropriate for large epidemiological studies (Table 2). In hospital-based care, many patients undergo endoscopy, which is then combined with an invasive test for H. pylori . Otherwise, breath tests and serology are commonly used. For children, fecal antigen tests offer the opportunity to assess H. pylori status without the need for endoscopy or vena puncture (Table 2). Although H. pylori is sensitive to a wide range of antibiotics in vitro, they all fail as monotherapy in vivo. In infected patients, the most effective single drug is clarithromycin, which leads to an approximate eradication rate of 40% when given twice daily for 10 to 14 days (237, 409, 504). The lack of efficacy of monotherapy is related to the niche of H. pylori , residing at lower pH in a viscous mucus layer. Dual therapies, combining twice-daily-dosed PPI with, in particular, amoxicillin, are still in use in some countries, but dual therapies have mostly been replaced by triple therapies. These combine two antibiotics with either a bismuth compound or a PPI. A further alternative is provided by quadruple therapies, which combine the bismuth compound and PPI with two antibiotics. The exact mode of action of bismuth compounds is unknown, but H. pylori is susceptible to these compounds both in vivo and in vitro (23, 349, 667). Tetracycline, amoxicillin, imidazoles (predominantly metronidazole and tinidazole), and a few selected macrolides (in particular clarithromycin, sometimes azithromycin) are probably the drugs most widely used for H. pylori eradication therapy (412). Recently, the use of rifabutin (502, 503) and furazolidone (152, 173, 245, 699) has been promoted. However, as their effectiveness is limited and many patients do not tolerate furazolidone, the primary use of these two antibiotics is a second-line rescue therapy of patients harboring metroni- dazole-resistant isolates (227, 410, 486). Occasionally the use of ciprofloxacin and related fluoroquinolones (131, 192) and other antibiotics, such as rifampin and streptomycin (544), has been reported, but these drugs seem to have no serious advantages over the aforementioned ones. The use of these drugs has resulted in effective therapies against H. pylori , with consistent eradication rates over 80%. Various treatment dura- tions, doses, and drug combinations have been studied, but none have consistently reached eradication levels in excess of 90 to 95%. Failures are in particular related to insufficient therapy adherence, often because of side effects, and to the presence of antimicrobial resistance. Such resistance is common in patients who have had previous antibiotic treatment, including failed eradication therapies (408). In the past decade, much effort has been devoted to the development of alternative treatments for H. pylori , in particular, vaccination. Colonization of the stomach with H. pylori results in the induction of a strong but unprotective inflammatory response, mainly polarized toward Th1 cells (432). It is currently believed that effective vaccination depends on the induction of a humoral and Th2 cell immune response. Muco- sal immunization with a variety of antigens in combination with mucosal adjuvants such as cholera toxin (AB5 toxin, CT), the heat-labile toxin of Escherichia coli , or Freund adjuvants, which induce a Th2 response, prevents or cures an infection by Helicobacter spp., while Th1 response-inducing adjuvants enhance inflammation rather than eliminating it. The first indications that these mucosal immunizations against Helicobacter induce a Th2 response were seen in studies showing specific salivary secretory immunoglobulin A (IgA) and serum IgG1 antibodies after oral immunization of mice (183, 355). Subsequent studies (543) indicated that mucosal immunization with ...
Context 3
... be the presence of a t(11;18) (q21;q21) translocation. This translocation is associated with API2-MALT1 fusion, the former being involved in regulation of apoptosis, the latter resembling a caspase-like protein, but with as-yet-unknown biological function. Together, the fusion leads to suppression of apoptosis. Several studies have reported that MALT lymphomas with this translocation do not at all or only rarely respond to H. pylori eradication (287, 371). GERD. GERD has long been considered to occur indepen- dently of H. pylori colonization, i.e., to occur with the same frequency and severity in H. pylori -positive and H. pylori -negative subjects. This opinion was based on cross-sectional observations which suggested that the prevalence of H. pylori among GERD patients was similar to that among controls (689). However, further studies suggested that H. pylori might protect against the development of GERD and as such also be of benefit to their hosts. This slowly emerging concept came from repeated observations of a low prevalence of H. pylori among GERD patients, particularly of more virulent strains (174); opposing time and geographical trends for H. pylori prevalence compared with the incidence of GERD and its complications; a potentially increased incidence of GERD after H. pylori eradication (347); and the recognition that H. pylori -induced corpus gastritis reduced acid secretion. The hypothesis was that H. pylori -induced inflammation of the gastric corpus had an acid-suppressive effect, thus preventing patients from contracting GERD. For individual subjects, these insights so far have limited relevance other than that they underline the concept that eradication therapy should be prescribed only when there is a clear indication for H. pylori diagnosis and treatment. There is, with further data having become available, no evidence that H. pylori eradication has a considerable impact on either the new development of GERD (641), the worsening of preexisting GERD when treatment has been withdrawn during disease remission (552), or preexistent GERD in remission during PPI maintenance therapy (335, 548). Together, these data show that although epidemiologic data suggest that there may be an inverse relation between H. pylori and GERD, the risk for new development or worsening of preexistent GERD is not an issue in the decision of whether or not to treat H. pylori . Extragastroduodenal disorders. H. pylori has been linked to a variety of extragastric disorders. These include coronary heart disease, dermatological disorders such as rosacea and idiopathic urticaria, autoimmune thyroid disease and thrombocytopenic purpura, iron deficiency anemia, Raynaud’s phenomenon, scleroderma, migraine, and Guillain-Barr ́ syn- drome. The underlying hypothetical mechanisms include chronic low-grade activation of the coagulation cascade, accel- erating atherosclerosis, and antigenic mimicry between H. pylori and host epitopes leading to autoimmune disorders (214). This has led to large numbers of case studies of patients with these disorders. Several groups in particular have studied patients with idiopathic thrombocytopenic purpura and showed that when these patients are colonized with H. pylori , eradication therapy has a significant effect over placebo for improvement of thrombocyte counts (215, 291, 612). H. pylori testing and treatment should be considered for these patients. In patients with the other conditions mentioned above, there is as yet no role for H. pylori eradication, and further adequate, randomized trials are needed (37, 343, 358). Infection with H. pylori results in a typical sequence of events, ultimately resulting in the development of gastric diseases. The sequence depicted in Fig. 5 was first suggested by Correa et al. (96) and has since been supported by many other studies. Colonization of the gastric mucosa by H. pylori first results in the induction of an inflammatory response, predominantly of the Th1 type. The initial acute gastritis is followed by active chronic gastritis, which lasts for life if the infection is not treated (340). Nevertheless, H. pylori -positive subjects are mostly unaware of this inflammation due to the lack of clinical symptoms. This inflammatory response is characterized by an influx of neutrophils, mononuclear cells, and T-helper 1 (Th1) cells, typically aimed at clearing intracellular infections (see “Im- mune Response,” below). However, H. pylori is not an intracellular pathogen, and thus the Th1 response results in epithelial cell damage rather than in the removal of H. pylori . The ongoing presence of H. pylori thus causes a lifelong proinflammatory response coupled to cellular damage and initiates the histological cascade depicted in Fig. 5. The continuous production of reactive oxygen species that results from the ongoing inflammation can give rise to DNA damage, thus inducing the multiple mutations thought to be required for initiation of the cancer cascade (Fig. 5). Various tests have been developed for the detection of H. pylori , each with their specific advantages and disadvantages (Table 2). The available tests are generally divided into invasive tests, based on gastric specimens for histology, culture, or other methods, and noninvasive tests, based on peripheral samples, such as blood, breath samples, stools, urine, or saliva for detection of antibodies, bacterial antigens, or urease activity. The choice of a specific test for an individual patient depends on local experience and the clinical setting (for reviews, see references 372, 640, and 713). In research protocols, a combination of two methods is often applied. In daily clinical practice, use of a single test is generally adequate, and most tests are sufficiently accurate to be used for this purpose. For routine diagnostic purposes, histology, urea breath testing, and culture are currently most often used, whereas the use of serology is most appropriate for large epidemiological studies (Table 2). In hospital-based care, many patients undergo endoscopy, which is then combined with an invasive test for H. pylori . Otherwise, breath tests and serology are commonly used. For children, fecal antigen tests offer the opportunity to assess H. pylori status without the need for endoscopy or vena puncture (Table 2). Although H. pylori is sensitive to a wide range of antibiotics in vitro, they all fail as monotherapy in vivo. In infected patients, the most effective single drug is clarithromycin, which leads to an approximate eradication rate of 40% when given twice daily for 10 to 14 days (237, 409, 504). The lack of efficacy of monotherapy is related to the niche of H. pylori , residing at lower pH in a viscous mucus layer. Dual therapies, combining twice-daily-dosed PPI with, in particular, amoxicillin, are still in use in some countries, but dual therapies have mostly been replaced by triple therapies. These combine two antibiotics with either a bismuth compound or a PPI. A further alternative is provided by quadruple therapies, which combine the bismuth compound and PPI with two antibiotics. The exact mode of action of bismuth compounds is unknown, but H. pylori is susceptible to these compounds both in vivo and in vitro (23, 349, 667). Tetracycline, amoxicillin, imidazoles (predominantly metronidazole and tinidazole), and a few selected macrolides (in particular clarithromycin, sometimes azithromycin) are probably the drugs most widely used for H. pylori eradication therapy (412). Recently, the use of rifabutin (502, 503) and furazolidone (152, 173, 245, 699) has been promoted. However, as their effectiveness is limited and many patients do not tolerate furazolidone, the primary use of these two antibiotics is a second-line rescue therapy of patients harboring metroni- dazole-resistant isolates (227, 410, 486). Occasionally the use of ciprofloxacin and related fluoroquinolones (131, 192) and other antibiotics, such as rifampin and streptomycin (544), has been reported, but these drugs seem to have no serious advantages over the aforementioned ones. The use of these drugs has resulted in effective therapies against H. pylori , with consistent eradication rates over 80%. Various treatment dura- tions, doses, and drug combinations have been studied, but none have consistently reached eradication levels in excess of 90 to 95%. Failures are in particular related to insufficient therapy adherence, often because of side effects, and to the presence of antimicrobial resistance. Such resistance is common in patients who have had previous antibiotic treatment, including failed eradication therapies (408). In the past decade, much effort has been devoted to the development of alternative treatments for H. pylori , in particular, vaccination. Colonization of the stomach with H. pylori results in the induction of a strong but unprotective inflammatory response, mainly polarized toward Th1 cells (432). It is currently believed that effective vaccination depends on the induction of a humoral and Th2 cell immune response. Muco- sal immunization with a variety of antigens in combination with mucosal adjuvants such as cholera toxin (AB5 toxin, CT), the heat-labile toxin of Escherichia coli , or Freund adjuvants, which induce a Th2 response, prevents or cures an infection by Helicobacter spp., while Th1 response-inducing adjuvants enhance inflammation rather than eliminating it. The first indications that these mucosal immunizations against Helicobacter induce a Th2 response were seen in studies showing specific salivary secretory immunoglobulin A (IgA) and serum IgG1 antibodies after oral immunization of mice (183, 355). Subsequent studies (543) indicated that mucosal immunization with urease resulted in a Th2 CD4 ϩ T-cell response that effectively eliminated an ongoing Helicobacter felis infection in BALB/c mice. Apparently, if a vaccine against H. pylori drives the immune response toward a Th2 response it can ...
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Citations
... Gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma have been associated with Helicobacter pylori, a causative agent of gastritis and peptic ulcers [23]. H. pylori's capacity to produce this range of illnesses is influenced by host, bacterial, and environmental variables [15,24]. Urease, flagella, adhesins, δ-glutamyltranspeptidase, lipopolysaccharide, and vacuolating, cytotoxin are some of the bacterial components required for H. pylori to colonize the stomach mucosa, remain for decades, and cause a severe inflammatory response that damages host cells [15]. ...
... Urease, flagella, adhesins, δ-glutamyltranspeptidase, lipopolysaccharide, and vacuolating, cytotoxin are some of the bacterial components required for H. pylori to colonize the stomach mucosa, remain for decades, and cause a severe inflammatory response that damages host cells [15]. Non-steroidal anti-inflammatory medicines (NSAID), alcohol, and smoking are examples of environmental factors, and host factors like gene polymorphism and immune response can also play a role [24]. Despite the stomach's unfavorable environment, H. pylori can use it as its principal site of colonization and survive there for years [1]. ...
... The four main steps necessary for H. pylori colonization and pathogenesis are as follows: (1) surviving in the acidic environment of the stomach; (2) moving toward epithelium cells through flagella-mediated motility; (3) attaching to host receptors by adhesins; and (4) inflicting tissue damage by releasing toxins [25]. At each crucial stage, H. pylori engages in a particular strategic activity to promote effective colonization, persistent infection, and disease pathogenesis [24]. In order to evade the stomach's acidic environment and spread a chronic infection, the pathogen first enters the host stomach lumen and then localizes to the antrum and corpus for adaption before it neutralizes the stomach's hostile acidic environment with its urease activity [26,27]. ...
Helicobacter pylori infection is a condition caused by the gram-negative bacterium H. pylori affecting the mucous lining of the antrum portion of the stomach. At least 50% of the global population fall victim to this condition with Africans proven to have the highest prevalence rate of 70%, followed by South America and Western Asia with 69.4 and 66.6% respectively. In Africa, Nigeria is said to have the highest prevalence rate of H. pylori infection recording 87.7 to 89.7%. H. pylori infection is known to inflict a wide range of gastric complications including Peptic ulcer disease among others, and extra gastric complications such as Neurological diseases, as well as Dermatological diseases. Psoriasis, an autoimmune chronic inflammatory disease of the skin, affecting more than 100 million individuals globally, is one of the dermatological complications of H. pylori infection. It has been noted that H. pylori seem to play a major role in the development of psoriasis. Therefore, this chapter seeks to provide readers with the connection between H. pylori infection and Psoriasis as well as the influence the treatment of H. pylori infection has on Psoriasis severity.
... From the mouth to the anus, the surface area of the mucosal epithelium of the digestive tract covers approximately 32 m 2 [1]. These specialised epithelial layers are continually exposed to aggressive and potentially damaging physical, chemical and biological conditions, including physical damage and shear forces from solid and potentially abrasive foods, gastric acid, bile, digestive enzymes and both symbiotic and pathogenic microorganisms [2][3][4]. The mucus barrier plays an essential role here, coating these epithelial surfaces (with the exception of the oesophagus and the mouth [5][6][7] and protecting the delicate tissues from these challenges while allowing absorption, secretion and host-microbe cross talk [8]. ...
MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin β-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease.
... pylori) bacteria, prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs), excessive alcohol consumption, and stress (3,4). H. pylori infects the stomach lining and is a major cause of GUs (5,6). H. pylori infection is very common, with an estimated 50-80% of people worldwide being infected (7). ...
Peptic ulcer disease is a common gastrointestinal disorder. The current treatment for gastric ulcers (GUs) is pharmacological interventions including antacids, mucosal defensive agents, H2-receptor blockers, proton pump inhibitors (PPIs) as well as antibiotics targeting H. pylori infections. Additionally, there has been an increasing focus on the application of natural treatments, such as pomegranate extracts, which have significant potential in the prevention and management of GUs. The therapeutic effects of pomegranate (Punica granatum) on GUs include its ability to inhibit ulcer formation, reduce gastric acidity, and promote the healing of gastric mucosal lesions. This is attributed to the antioxidant, anti-inflammatory, and antimicrobial properties of the active constituents in pomegranate such as polyphenols, flavonoids, tannins, and anthocyanins. The results of this study showed that pomegranate extracts could significantly suppress gastric ulceration, reduce tissue lipid peroxidation, and enhance the levels of antioxidative enzymes. Pomegranate exerts its anti-inflammatory effects through the suppression of pro-inflammatory cytokine synthesis, including TNF-α, IL-1β, and IL-6. Additionally, pomegranate extracts increase the production of gastric mucosal protective factors such as PGE2 and NO, and have antimicrobial activity against H. pylori. Overall, while pomegranate showed promise as a natural remedy for the prevention and management of GUs, further research is needed to optimize its therapeutic efficacy.
... In contrast to other bacterial pathogens, H. pylori has demonstrated a higher genetic heterogeneity due to the gastric adaptation. Its low clonality has led to genetic and phenotypical cells, which can be more susceptible than other tested Gram-negative species [28]. Finally, LCC exhibited antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium kansasii, with MIC values ranging from 31.2 µg/mL to 125 µg/mL. ...
Drug-resistant bacteria constitute a big barrier against current pharmacotherapy. Efforts are urgent to discover antibacterial drugs with novel chemical and biological features. Our work aimed at the synthesis, evaluation of antibacterial effects, and toxicity of licochalcone C (LCC), a naturally occurring chalcone. The synthetic route included six steps, affording a 10% overall yield. LCC showed effects against Gram-positive bacteria (MIC = 6.2–50.0 µg/mL), Mycobacterium species (MIC = 36.2–125 µg/mL), and Helicobacter pylori (MIC = 25 µg/mL). LCC inhibited the biofilm formation of MSSA and MRSA, demonstrating MBIC50 values of 6.25 μg/mL for both strains. The investigations by fluorescence microscopy, using PI and SYTO9 as fluorophores, indicated that LCC was able to disrupt the S. aureus membrane, similarly to nisin. Systemic toxicity assays using Galleria mellonella larvae showed that LCC was not lethal at 100 µg/mL after 80 h treatment. These data suggest new uses for LCC as a compound with potential applications in antibacterial drug discovery and medical device coating.
... [7][8][9] Hence, accurate diagnosis of H. pylori infection is crucial in the management strategy to minimize the H. pylori-related gastropathologies and gastric cancer. 10 Several invasive and non-invasive diagnostic tests are available for the detection of infection with this pathogen. Invasive tests, which require endoscopic surgery and biopsy specimens, offer the possibility to explore gastric mucosa during endoscopic examination. ...
Background and Aim
Helicobacter pylori represents the major pathogen in the pathophysiology of diverse gastrointestinal conditions. This study sought to determine the endoscopic aspect of the gastric mucosa in relation to H. pylori infection in Cameroon.
Methods
This study was conducted in three reference health facilities in Cameroon from October 2020 to October 2022. The study enrolled 494 consecutive volunteer dyspeptic patients attending to the gastroenterology department of the selected health facilities. A description of the aspect of gastric mucosa of all participants was performed during endoscopy examination, and biopsies were collected for H. pylori detection using rapid urease tests.
Results
Gastritis, ulcerated lesions, duodenitis, esophagitis, normal mucosa aspect, bulbitis, and gastric neoplastic lesions were found in 40.1, 22.3, 10.9, 10.3, 9.7, 6.3, and 0.40% of biopsy samples, respectively. Erythematous/exudative (45.9%) and enterogastric reflux (12.2%) were the main gastritis types recorded. H. pylori was present in 58.1, 46.3, 87.1, 66.7, and 61.8% in gastritis, duodenitis, bulbitis, esophagitis, and ulcerated lesions, respectively. A positive relationship was noticed between the presence of H. pylori and gastritis (1.037 [0.720–1.493]; P = 0.845), bulbitis (4.237 [1.602–11.235]; P = 0.004), esophagitis (1.515 [0.822–2.793]; P = 0.183), ulcerated lesions (1.233 [0.798–1.904]; P = 0.345), erythematous/exudative gastritis (1.354 [0.768–2.389]; P = 0.295), and enterogastric reflux gastritis (1.159 [0.492–2.733]; P = 0.736).
Conclusion
Gastritis and erythematous/exudative gastritis are the most frequent gastrointestinal pathophysiology conditions in dyspeptic patient in our milieu. H. pylori infection is responsible for 94.8% of the gastrointestinal pathophysiology conditions with bulbitis as the condition is significantly associated with this bacterium infection.
... Hop P and gastric disorders: Numerous studies have investigated an association between SabA and clinical outcomes. It appears that SabA is responsible for inflammation and its presence is correlated with clinical outcomes [109,110]. Also, a close relationship between this protein and gastric cancer has been found. In one study, 66% of H. pylori strains in patients with gastritis were SabA-positive, 44% were positive in individuals with duodenal ulcers and 70% in cases of gastric cancer [111]. ...
Helicobacter pylori is a gastric oncopathogen that infects over half of the world’s human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost the pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.
... The nervous system disorders with internal diseases are challenging medical and social issues, considering their prevalence and impact on patients' life quality and working ability [7,8]. Currently, there is a significant increase in psychosomatic illnesses, and the phenomenon of affecting more younger people by them. ...
... Given that the digestive system functioning is closely associated with the nervous system regulatory mechanisms, many gastrointestinal diseases are psychosomatic. Psychosomatic relationships in duodenal ulcer remain among the current issues of modern gastroenterology [7,8]. ...
... Peptic ulcer disease has been high on the list in the overall structure of the digestive diseases, it affects from 6.0 to 10.0 % of the population in developed countries, and the mortality ranges from 6 to 9.7 cases per 100,000 population [7,8,14]. From a modern viewpoint, it is considered to be a polyetiological, genetically and pathogenetically heterogeneous disease, which is based on the systemic response of the whole human body to the influence of etiological factors, including Helicobacter pylori (H.pуlori), overwhelmingly gastric and duodenal mucosal lesions, against the background of the adaptive hierarchy irregularity [2,7,14]. ...
Background. The purpose was to study the effect of Helicobacter pylori (H.pylori) in duodenal ulcer on the neuropsychological and psychometric scores. Materials and methods. We conducted a comprehensive clinical, neurological, neuropsychological, and psychometric examination of 60 patients with duodenal ulcer aged 25–60 (the mean of 39.80 ± 1.29) years. All of them were divided into two groups considering whether H.pylori infection was detected (group 1) or not (group 2). The control group included 30 apparently healthy individuals with no somatic abnormalities. To study psychometric and neuropsychological characteristics, the patients were comprehensively tested, in particular using the Beck Depression Inventory for evaluating the severity of depression, the State-Trait Anxiety Inventory for assessing separate dimensions of state and trait anxiety, the Well-being, Activity, Mood (WAM) questionnaire, the Mini-Mental Health Examination for screening cognitive function, the Schulte tables for evaluating the refocusing speeds and performance distribution. Results. The level of depression in H.pylori-positive duodenal ulcer was significantly higher than with H.pylori-negative duodenal ulcer (p < 0.05). The patients from the group 1 had higher scores of state and trait anxiety and the lower ones of the functional state. The concentration of attention detected by means of the Schulte tables was lower in these patients. A direct correlation was found between the degree of depressive disorders and the number of complaints associated with psycho-emotional disorders in the patients with duodenal ulcer (r = 0.61). We found an inverse correlation (p < 0.05) between the anxiety level and the WAM indices, on the one hand, and between depressive disorders and the WAM indices, on the other hand, in the patients with duodenal ulcer. Depression and anxiety were comorbid in 73.3 % of cases in the group 1 and in 30 % of cases in the group 2. Conclusions. The complaints associated with psycho-emotional disorders occurred in the patients with both H.pylori-positive and H.pylori-negative duodenal ulcer; however, they were more frequent in the group 1. The clinical presentations of depression were observed in both groups, but the depression level was significantly higher in the patients with H.pylori-positive duodenal ulcer (p < 0.05). An increase in anxiety was also found in both groups; however, the rates of state and trait anxiety were higher in the group 1. At duodenal ulcer exacerbation, no matter if H.pylori infection was present or not, the patients had unsatisfactory well-being, low activity, and poor mood. The decreased indices of the functional state self-assessment were detected in the group with H.pylori-positive duodenal ulcer. Using the Schulte tables, we found that a decrease in attention concentration was more evident in the group 1 that in the patients with H.pylori-negative duodenal ulcer. Thus, having conducted the neuropsychological and psychometric testing, we conclude that H.pylori infection has not been the main cause of psycho-emotional disorders in duodenal ulcer, but if the patients were infected, the dysfunction was more severe. It was subject to the increased frequency of psycho-emotional complaints, the deterioration in the patients’ sense of well-being, the increased levels of anxiety and depressive disorders.
... Helicobacter pylori is a Gram-negative bacterium infecting over half of the world's population (Hooi et al, 2017). H. pylori colonization of the stomach results in gastric inflammation (gastritis) and an increased risk for the development of gastric cancer, peptic ulcer disease, and mucosa-associated lymphoid tissue lymphoma (Atherton, 2006;Kusters et al, 2006;Malfertheiner et al, 2023). H. pylori strains harboring the cag pathogenicity island (cag PAI), a 40kb chromosomal region that encodes a type IV secretion system (T4SS) and the secreted effector protein CagA, are more frequently associated with gastric cancer and peptic ulcer disease, compared with cag PAI-negative strains (Blaser et al, 1995;Parsonnet et al, 1997;Nomura et al, 2002;Plummer et al, 2007;Cover, 2016;Tran et al, 2024). ...
The Helicobacter pylori Cag type IV secretion system (Cag T4SS) has an important role in the pathogenesis of gastric cancer. The Cag T4SS outer membrane core complex (OMCC) is organized into three regions: a 14-fold symmetric outer membrane cap (OMC) composed of CagY, CagX, CagT, CagM, and Cag3; a 17-fold symmetric periplasmic ring (PR) composed of CagY and CagX; and a stalk with unknown composition. We investigated how CagT, CagM, and a conserved antenna projection (AP) region of CagY contribute to the structural organization of the OMCC. Single-particle cryo-EM analyses showed that complexes purified from Δ cagT or Δ cagM mutants no longer had organized OMCs, but the PRs remained structured. OMCCs purified from a CagY antenna projection mutant (CagY ∆ AP) were structurally similar to WT OMCCs, except for the absence of the α-helical antenna projection. These results indicate that CagY and CagX are sufficient for maintaining a stable PR, but the organization of the OMC requires CagY, CagX, CagM, and CagT. Our results highlight an unexpected structural independence of two major subdomains of the Cag T4SS OMCC.
... Drug and alcohol abuse, alcoholism, endocrine dyscrasia, and bacterial H. pylori infections are some of the key factors that trigger the ulcer incidences in the stomach (Kusters et al., 2006;Drini 2017). Ethanol is a toxic chemical that, after a few days, induces noticeable vascular alterations and reduces stomach mucus (Moleiro et al., 2009). ...
The beneficial effects of orchids as a medicinal plant have been highlighted in a number of widely used medical practices. The current study has deciphered the gastro-protective effects of Acampe ochracea methanol extract (AOCE), Aerides odorata methanol extract (AOE), Cymbidium aloifolium methanol extract (CAE), and Papilionanthe teres methanol extract (PTE) in ethanol-induced ulcer. Long-Evan rats fasted; different treatment groups were administered the samples as mentioned earlier (250 and 500 mg/kg) orally; distilled water and esomeprazole (20 mg/kg p.o., b.w.) were used as normal control and standard drugs; thereafter, they received 0.5 mL of an 80 % (v/v) ethanol solution an hour later. By suppressing ulceration of the mucosal layer and altering the biochemical features of gastric juice, including the levels of carbohydrate, protein, and pep-sin, the findings showed that therapy with treatments (500 mg/kg) remarkably (p < 0.001) modulated the ulcer and protected the integrity of gastric mucosa. Furthermore, treatments notably (p < 0.001, and p < 0.01) elevated the levels of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) and markedly (p < 0.001, and p < 0.01) decreased malondialdehyde (MDA) levels. Moreover, protecting the normal architecture of the stomach section from EtOH toxicity, the treatments unveiled notable protection from disruption of the membrane of epithelial cells and limited edema in the submucosal layer. Hence, the outcome of the investigation deciphered that the following orchids: A. ochra-cea, A. odorata, C. aloifolium, and P. teres might be therapeutic candidates for managing peptic ulcer disorders (PUD).
... Colonization with H. pylori increases the risk of developing gastrointestinal disorders, with the pattern and severity of gastritis determining which disorder can develop (Kusters et al., 2006). Since inflammation leads to the degeneration of epithelial cells, gastritis often leads to the formation of ulcers (Narayanan et al., 2018). ...
... Studies have noted a strong correlation between H. pylori infections and the presence of ulcers, with 85% of gastric ulcers and 95% of duodenal ulcers occurring along with H. pylori infections (Testerman and Morris, 2014;Narayanan et al., 2018). Peptic ulcer disease was noted to recur within a year in approximately 50% of patients infected with H. pylori (Kusters et al., 2006). ...
