Helicobacter pylori infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during H. pylori infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon H. pylori stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, H. pylori LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. H. pylori infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in H. pylori infection include EGFR, FAK, and Wnt/β-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, H. pylori infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer.

Introdução: A infecção por Helicobacter pylori (H. pylori) tem distribuição geográfica universal, porém apresenta grande variabilidade na prevalência, nos fatores de virulência e na apresentação clínica de acordo com a população estudada. No Brasil, um país continental composto por etnias e hábitos culturais diversos, o comportamento da infecção também parece variar conforme já demonstrado em diferentes estudos. O presente estudo foi realizado com o objetivo de descrever a prevalência da infecção por cepas de H. pylori cagA-positivo em um grupo de crianças e adolescentes submetidos a esofagogastroduodenoscopia (EGD) em Porto Alegre, cidade situada na região Sul do Brasil. Materiais e Método: Noventa e oito fragmentos de biópsia gástrica de crianças e adolescentes foram submetidos à pesquisa de cepas de H. pylori cagA-positivo pelo método da reação em cadeia da polimerase (PCR). Resultados: A prevalência de cepas de H. pylori cagA-positivo foi de 29,6% (IC95% 18 a 43,6%). Não foram encontradas diferenças estatisticamente significativas quanto às características clínicas, demográficas, endoscópicas e histológicas dos pacientes infectados por cepas cagA-positivo em relação aos infectados por cepas cagA-negativo. Conclusões: O estudo demonstrou uma baixa prevalência da infecção por cepas de H. pylori cagA-positivo em crianças e adolescentes submetidos à EGD no sul do Brasil em comparação a estudos realizados com crianças de outras regiões do Brasil. Não houve associação entre a presença de cepas cagA-positivo e apresentação clínica adversa na amostra estudada. / Introdution: Helicobacter pylori (H. pylori) has a worldwide distribution, but the prevalence of infection, virulence factors, and clinical presentation vary widely according to the studied population. In Brazil, a continental country composed of several ethnicities and cultural habits, the behavior of infection also appears to vary, as many other studies have shown. Objective: The present study aimed to describe the prevalence of infection with cagApositive H. pylori strains in a group of children and adolescents who underwent esophagogastroduodenoscopy (EGD) in Porto Alegre, a city in Southern Brazil. Methods: Ninety-eight gastric biopsy specimens of children and adolescents were tested for presence of H. pylori cagA-positive strains by the polymerase chain reaction (PCR) method. Results: The prevalence of H. pylori cagA-positive strains was 29.6% (IC95% from 18 to 43.6%). There were no statistically significant differences in clinical or demographic characteristics or in the endoscopic and histological features of patients infected with cagA-positive strains as compared with those infected by cagA-negative strains. Conclusions: The study showed a low prevalence of infection with cagA-positive H. pylori strains among children and adolescents who underwent EGD in southern Brazil, in comparison to studies conducted with children from other regions of Brazil. There was no association between the presence of cagA-positive strains and more severe clinical presentations in the studied sample.

Introdução: Recentemente, vários estudos têm investigado e até mesmo sugerindo a bactéria Helicobacter pylori como um importante componente no desenvolvimento de eventos restritos ou não ao trato gastrintestinal. A relação já bastante elucidada acerca da relação entre os fatores bacterianos de virulência e o risco aumentado para úlcera péptica e adenocarcinoma gástrico parece não estar muito definida em se tratando de alterações em marcadores de inflamação aguda, como a proteína C reativa (PCR), em indivíduos infectados pelas cepas mais virulentas do microrganismo. Neste trabalho, nós avaliamos a presença de H. pylori, virulência bacteriana e níveis séricos de PCR em pacientes dispépticos funcionais. Materiais e métodos: Estudo transversal que incluiu 489 indivíduos saudáveis com diagnóstico de dispepsia funcional firmado através de critérios do Consenso de Roma III. Após avaliação clínica e endoscópica, os pacientes foram incluídos por não apresentarem qualquer causa orgânica que pudesse estar relacionada aos sintomas de dispepsia. A presença da bactéria foi diagnosticada através de análise histológica e teste rápido da urease dos fragmentos biopsiados. Os níveis séricos de PCR foram obtidos por imunonefelometria e o status para o fator de virulência CagA foi determinado através de ensaio comercial imunoenzimático. Resultados: A prevalência de H. pylori foi de 66,3% e a presença de anticorpos anti-CagA foi detectada em aproximadamente 43% das amostras positivas. Houve uma associação estatisticamente significativa entre o consumo de chimarrão e a presença da bactéria. Observou-se um efeito importante da infecção por H. pylori na inflamação local, estimada através da atividade inflamatória e grau de inflamação do epitélio gástrico. Não foi constatada resposta inflamatória sistêmica ao patógeno através da dosagem de PCR, independente do status de virulência bacteriana. Conclusão: Na população de indivíduos disépticos funcionais avaliada, a bactéria parece não desencadear qualquer resposta inflamatória sistêmica, estando a virulência bacteriana associada a um maior grau e atividade inflamatória do epitélio gástrico. / Background: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C reactive protein (CRP), with the pathogen. We evaluated the presence of H. pylori, bacterial virulence and CRP serum levels in individuals diagnosed with functional dyspepsia. Materials and Methods: Transversal study that evaluated 489 healthy individuals well characterized according to Rome III Consensus for the diagnosis of functional dyspepsia. The study population underwent to an endoscopic investigation and did not present any organic explanation for their symptoms. The bacterial infection was established by histology and urease rapid test. The levels of serum CRP were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined trough a commercial imunoenzimatic assay. Results: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. We found a statistically significant relationship between yerba mate tea consumption and positive H. pylori status. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. No systemic response to the pathogen, measured through CRP levels, was observed, regardless of CagA status. Conclusion: In our study population, the presence of H. pylori seems not to be related with any important systemic inflammatory response. Bacterial virulence was related to a higher inflammation and inflammatory activity in gastric epithelium.

xi, 62 p. : ill. (some col.) / This dissertation describes research into microbial influences on host signaling in the zebrafish intestine. Vertebrate organisms are consistently exposed to microbes, especially on epithelial tissues that are exposed to the environment, such as the skin and the gastrointestinal tract. The close association between these tissues and microbes over time has resulted in a symbiotic state, whereby microorganisms have gained the ability to utilize vertebrate epithelia as a niche for replication and the acquisition of nutrients. These associations run the gamut from beneficial to exceedingly pathogenic and often involve complex bidirectional signaling between microbe and host. Microbial signals can interact with host cell pathways involved in a wide range of cellular processes. Here, we describe our investigations into one such pathway, the Wnt signaling pathway, and how microbial activation of Wnt signaling can translate into alterations in cell proliferation and homeostasis in the intestinal epithelium of the teleost fish Danio rerio. We report that epithelial cell proliferation in the developing zebrafish intestine is stimulated both by the presence of the resident microbiota and by activation of Wnt signaling and demonstrate that resident intestinal bacteria enhance the stability of β-catenin in intestinal epithelial cells, promoting cell proliferation in the developing vertebrate intestine. We also describe how transgenic expression of the bacterial effector protein CagA from the human gastric pathogen Helicobacter pylori is capable of causing significant overproliferation of the intestinal epithelium and adult intestinal hyperplasia, as well as significant upregulation of the Wnt target genes cyclinD1 and the zebrafish c-myc ortholog myca. We show that co-expression of CagA with a mutant allele of the β-catenin destruction complex protein Axin1 resulted in a further increase in intestinal proliferation, while co-expression of CagA with a null allele of the essential β-catenin transcriptional cofactor Tcf4 restored intestinal proliferation to wild-type levels. These results suggest that CagA activates canonical Wnt signaling downstream of the β-catenin destruction complex and upstream of Tcf4. Our studies provide in vivo evidence of Wnt pathway activation by CagA and implicate this activation in CagA-induced epithelial overproliferation, an early step in gastrointestinal cancer development. This dissertation contains both my previously published and unpublished co-authored material. / Committee in charge: Dr. Judith Eisen, Chairperson; Dr. Karen Guillemin, Advisor; Dr. Tory Herman, Member; Dr. Hui Zong, Member; Dr. Kenneth Prehoda, Outside Member

Introdução: Recentemente, vários estudos têm investigado e até mesmo sugerindo a bactéria Helicobacter pylori como um importante componente no desenvolvimento de eventos restritos ou não ao trato gastrintestinal. A relação já bastante elucidada acerca da relação entre os fatores bacterianos de virulência e o risco aumentado para úlcera péptica e adenocarcinoma gástrico parece não estar muito definida em se tratando de alterações em marcadores de inflamação aguda, como a proteína C reativa (PCR), em indivíduos infectados pelas cepas mais virulentas do microrganismo. Neste trabalho, nós avaliamos a presença de H. pylori, virulência bacteriana e níveis séricos de PCR em pacientes dispépticos funcionais. Materiais e métodos: Estudo transversal que incluiu 489 indivíduos saudáveis com diagnóstico de dispepsia funcional firmado através de critérios do Consenso de Roma III. Após avaliação clínica e endoscópica, os pacientes foram incluídos por não apresentarem qualquer causa orgânica que pudesse estar relacionada aos sintomas de dispepsia. A presença da bactéria foi diagnosticada através de análise histológica e teste rápido da urease dos fragmentos biopsiados. Os níveis séricos de PCR foram obtidos por imunonefelometria e o status para o fator de virulência CagA foi determinado através de ensaio comercial imunoenzimático. Resultados: A prevalência de H. pylori foi de 66,3% e a presença de anticorpos anti-CagA foi detectada em aproximadamente 43% das amostras positivas. Houve uma associação estatisticamente significativa entre o consumo de chimarrão e a presença da bactéria. Observou-se um efeito importante da infecção por H. pylori na inflamação local, estimada através da atividade inflamatória e grau de inflamação do epitélio gástrico. Não foi constatada resposta inflamatória sistêmica ao patógeno através da dosagem de PCR, independente do status de virulência bacteriana. Conclusão: Na população de indivíduos disépticos funcionais avaliada, a bactéria parece não desencadear qualquer resposta inflamatória sistêmica, estando a virulência bacteriana associada a um maior grau e atividade inflamatória do epitélio gástrico. / Background: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C reactive protein (CRP), with the pathogen. We evaluated the presence of H. pylori, bacterial virulence and CRP serum levels in individuals diagnosed with functional dyspepsia. Materials and Methods: Transversal study that evaluated 489 healthy individuals well characterized according to Rome III Consensus for the diagnosis of functional dyspepsia. The study population underwent to an endoscopic investigation and did not present any organic explanation for their symptoms. The bacterial infection was established by histology and urease rapid test. The levels of serum CRP were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined trough a commercial imunoenzimatic assay. Results: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. We found a statistically significant relationship between yerba mate tea consumption and positive H. pylori status. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. No systemic response to the pathogen, measured through CRP levels, was observed, regardless of CagA status. Conclusion: In our study population, the presence of H. pylori seems not to be related with any important systemic inflammatory response. Bacterial virulence was related to a higher inflammation and inflammatory activity in gastric epithelium.

Introdução: A infecção por Helicobacter pylori (H. pylori) tem distribuição geográfica universal, porém apresenta grande variabilidade na prevalência, nos fatores de virulência e na apresentação clínica de acordo com a população estudada. No Brasil, um país continental composto por etnias e hábitos culturais diversos, o comportamento da infecção também parece variar conforme já demonstrado em diferentes estudos. O presente estudo foi realizado com o objetivo de descrever a prevalência da infecção por cepas de H. pylori cagA-positivo em um grupo de crianças e adolescentes submetidos a esofagogastroduodenoscopia (EGD) em Porto Alegre, cidade situada na região Sul do Brasil. Materiais e Método: Noventa e oito fragmentos de biópsia gástrica de crianças e adolescentes foram submetidos à pesquisa de cepas de H. pylori cagA-positivo pelo método da reação em cadeia da polimerase (PCR). Resultados: A prevalência de cepas de H. pylori cagA-positivo foi de 29,6% (IC95% 18 a 43,6%). Não foram encontradas diferenças estatisticamente significativas quanto às características clínicas, demográficas, endoscópicas e histológicas dos pacientes infectados por cepas cagA-positivo em relação aos infectados por cepas cagA-negativo. Conclusões: O estudo demonstrou uma baixa prevalência da infecção por cepas de H. pylori cagA-positivo em crianças e adolescentes submetidos à EGD no sul do Brasil em comparação a estudos realizados com crianças de outras regiões do Brasil. Não houve associação entre a presença de cepas cagA-positivo e apresentação clínica adversa na amostra estudada. / Introdution: Helicobacter pylori (H. pylori) has a worldwide distribution, but the prevalence of infection, virulence factors, and clinical presentation vary widely according to the studied population. In Brazil, a continental country composed of several ethnicities and cultural habits, the behavior of infection also appears to vary, as many other studies have shown. Objective: The present study aimed to describe the prevalence of infection with cagApositive H. pylori strains in a group of children and adolescents who underwent esophagogastroduodenoscopy (EGD) in Porto Alegre, a city in Southern Brazil. Methods: Ninety-eight gastric biopsy specimens of children and adolescents were tested for presence of H. pylori cagA-positive strains by the polymerase chain reaction (PCR) method. Results: The prevalence of H. pylori cagA-positive strains was 29.6% (IC95% from 18 to 43.6%). There were no statistically significant differences in clinical or demographic characteristics or in the endoscopic and histological features of patients infected with cagA-positive strains as compared with those infected by cagA-negative strains. Conclusions: The study showed a low prevalence of infection with cagA-positive H. pylori strains among children and adolescents who underwent EGD in southern Brazil, in comparison to studies conducted with children from other regions of Brazil. There was no association between the presence of cagA-positive strains and more severe clinical presentations in the studied sample.

Introdução: Recentemente, vários estudos têm investigado e até mesmo sugerindo a bactéria Helicobacter pylori como um importante componente no desenvolvimento de eventos restritos ou não ao trato gastrintestinal. A relação já bastante elucidada acerca da relação entre os fatores bacterianos de virulência e o risco aumentado para úlcera péptica e adenocarcinoma gástrico parece não estar muito definida em se tratando de alterações em marcadores de inflamação aguda, como a proteína C reativa (PCR), em indivíduos infectados pelas cepas mais virulentas do microrganismo. Neste trabalho, nós avaliamos a presença de H. pylori, virulência bacteriana e níveis séricos de PCR em pacientes dispépticos funcionais. Materiais e métodos: Estudo transversal que incluiu 489 indivíduos saudáveis com diagnóstico de dispepsia funcional firmado através de critérios do Consenso de Roma III. Após avaliação clínica e endoscópica, os pacientes foram incluídos por não apresentarem qualquer causa orgânica que pudesse estar relacionada aos sintomas de dispepsia. A presença da bactéria foi diagnosticada através de análise histológica e teste rápido da urease dos fragmentos biopsiados. Os níveis séricos de PCR foram obtidos por imunonefelometria e o status para o fator de virulência CagA foi determinado através de ensaio comercial imunoenzimático. Resultados: A prevalência de H. pylori foi de 66,3% e a presença de anticorpos anti-CagA foi detectada em aproximadamente 43% das amostras positivas. Houve uma associação estatisticamente significativa entre o consumo de chimarrão e a presença da bactéria. Observou-se um efeito importante da infecção por H. pylori na inflamação local, estimada através da atividade inflamatória e grau de inflamação do epitélio gástrico. Não foi constatada resposta inflamatória sistêmica ao patógeno através da dosagem de PCR, independente do status de virulência bacteriana. Conclusão: Na população de indivíduos disépticos funcionais avaliada, a bactéria parece não desencadear qualquer resposta inflamatória sistêmica, estando a virulência bacteriana associada a um maior grau e atividade inflamatória do epitélio gástrico. / Background: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C reactive protein (CRP), with the pathogen. We evaluated the presence of H. pylori, bacterial virulence and CRP serum levels in individuals diagnosed with functional dyspepsia. Materials and Methods: Transversal study that evaluated 489 healthy individuals well characterized according to Rome III Consensus for the diagnosis of functional dyspepsia. The study population underwent to an endoscopic investigation and did not present any organic explanation for their symptoms. The bacterial infection was established by histology and urease rapid test. The levels of serum CRP were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined trough a commercial imunoenzimatic assay. Results: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. We found a statistically significant relationship between yerba mate tea consumption and positive H. pylori status. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. No systemic response to the pathogen, measured through CRP levels, was observed, regardless of CagA status. Conclusion: In our study population, the presence of H. pylori seems not to be related with any important systemic inflammatory response. Bacterial virulence was related to a higher inflammation and inflammatory activity in gastric epithelium.

Introdução: A infecção por Helicobacter pylori (H. pylori) tem distribuição geográfica universal, porém apresenta grande variabilidade na prevalência, nos fatores de virulência e na apresentação clínica de acordo com a população estudada. No Brasil, um país continental composto por etnias e hábitos culturais diversos, o comportamento da infecção também parece variar conforme já demonstrado em diferentes estudos. O presente estudo foi realizado com o objetivo de descrever a prevalência da infecção por cepas de H. pylori cagA-positivo em um grupo de crianças e adolescentes submetidos a esofagogastroduodenoscopia (EGD) em Porto Alegre, cidade situada na região Sul do Brasil. Materiais e Método: Noventa e oito fragmentos de biópsia gástrica de crianças e adolescentes foram submetidos à pesquisa de cepas de H. pylori cagA-positivo pelo método da reação em cadeia da polimerase (PCR). Resultados: A prevalência de cepas de H. pylori cagA-positivo foi de 29,6% (IC95% 18 a 43,6%). Não foram encontradas diferenças estatisticamente significativas quanto às características clínicas, demográficas, endoscópicas e histológicas dos pacientes infectados por cepas cagA-positivo em relação aos infectados por cepas cagA-negativo. Conclusões: O estudo demonstrou uma baixa prevalência da infecção por cepas de H. pylori cagA-positivo em crianças e adolescentes submetidos à EGD no sul do Brasil em comparação a estudos realizados com crianças de outras regiões do Brasil. Não houve associação entre a presença de cepas cagA-positivo e apresentação clínica adversa na amostra estudada. / Introdution: Helicobacter pylori (H. pylori) has a worldwide distribution, but the prevalence of infection, virulence factors, and clinical presentation vary widely according to the studied population. In Brazil, a continental country composed of several ethnicities and cultural habits, the behavior of infection also appears to vary, as many other studies have shown. Objective: The present study aimed to describe the prevalence of infection with cagApositive H. pylori strains in a group of children and adolescents who underwent esophagogastroduodenoscopy (EGD) in Porto Alegre, a city in Southern Brazil. Methods: Ninety-eight gastric biopsy specimens of children and adolescents were tested for presence of H. pylori cagA-positive strains by the polymerase chain reaction (PCR) method. Results: The prevalence of H. pylori cagA-positive strains was 29.6% (IC95% from 18 to 43.6%). There were no statistically significant differences in clinical or demographic characteristics or in the endoscopic and histological features of patients infected with cagA-positive strains as compared with those infected by cagA-negative strains. Conclusions: The study showed a low prevalence of infection with cagA-positive H. pylori strains among children and adolescents who underwent EGD in southern Brazil, in comparison to studies conducted with children from other regions of Brazil. There was no association between the presence of cagA-positive strains and more severe clinical presentations in the studied sample.

infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in infection include EGFR, FAK, and Wnt/β-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer.

Helicobacter pylori est associée à des pathologies gastro-duodénales sévères mais est également un marqueur bactérien de migrations humaines. Nous avons montré que des populations génétiques distinctes de H. pylori ont accompagné au moins quatre migrations en Asie du sud-est et en Océanie : i) une expansion des ancêtres des austronésiens il y a 5000 ans à partir de Taiwan en Océanie, ii) une migration d’Inde en Asie du sud-est depuis 2000 ans,iii) une migration des ancêtres des locuteurs des langues austro-asiatiques au Vietnam et auCambodge il y a 4000 ans, i) une migration des ancêtres des Thaïs du sud de la Chine vers l’actuelle Thaïlande au début du second millénaire. Ces données confirment la résolution plus élevée de la diversité génétique de H. pylori pour retracer les anciennes migrations humaines par comparaison aux marqueurs génétiques humains traditionnels. Nous avons ensuite investigué les facteurs de virulence de souches isolées de patients présentant des symptômes gastriques au Sénégal et au Cambodge. Au Sénégal, une association significative a été observée entre le cancer gastrique et le gène cagA, deux motifs EPIYA-C et l’allèle vacA s1. De multiples segments EPIYA-C étaient observés moins fréquemment que dans les autres régions du monde, contribuant probablement à la faible incidence du cancer gastrique. Au Cambodge, une introgression fréquente d’allèles cagA et vacA européens dans des souches d’Asie de l’est a été observée. CagA et VacA ayant des effets antagonistes, cette expansion pourrait entraîner la rupture de l’équilibre entre les effets biologiques de ces deux protéines et être responsable de conséquences graves sur l’évolution de la maladie. / Helicobacter pylori is associated with severe gastroduodenal disorders but is also a bacterial genetic marker of human migrations. First, we provide evidence that distinct H. pylori genetic populations accompanied at least four ancient human migrations into Oceania and Southeast Asia: i) an expansion of Austronesian speaking people about 5000 years ago from Taiwan into Oceania, ii) a migration from India into Southeast Asia within the last 2000 years, iii) a migration of Austro-Asiatic speaking people into Vietnam and Cambodia about 4000 years ago, and iv) a migration of the ancestors of the Thai people from Southern China into Thailand during the early second millennium AD. These findings demonstrate that H. pylori genetic diversity has more discriminatory power than traditional human genetic markers for tracing old human migrations. Second, we investigated virulence factors of H. pylori strains isolated from patients with gastric symptoms in Senegal and Cambodia. In Senegal, a significant association was observed between gastric cancer and the cagA gene, two EPIYA-C segments, and the s1 vacA allele in Senegal. Multiple EPIYA-C segments were less frequent than reported in other countries, possibly contributing to the low incidence of gastric cancer. In Cambodia, the frequent introgression of European vacA and cagA alleles into East Asian H. pylori strains was observed. As VacA and CagA have opposing effects, this expansion may disrupt the balancing activities on epithelial cells which might result in severe consequences for individual disease outcome.