Abstract
Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
| Original language | English |
|---|---|
| Article number | 8184 |
| Journal | Nature Communications |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Bibliographical note
Publisher Copyright:© 2023, The Author(s).
Funding
Our special thanks are extended to all the individuals who were the hosts of the strains of the Hp GP collection, who represent the human populations that bear the burden of H. pylori -associated disease, and whose biological samples serve to advance research aimed at reducing this disease burden. We immensely thank Lisa D. Finkelstein, Ramona Bhattacharya, Jillian M. Varonin, Mary Jane Williams, Karen Williams Kinney, and Melissa A. Raymond from the US National Institutes of Health (National Cancer Institute’s Technology Transfer Center, National Cancer Institute’s Division of Cancer Epidemiology, and Genetics, and Division of Logistic Services) for their administrative and logistic support in establishing the collaboration agreements and importing the multiple sets of biospecimens. We also thank the US Centers for Disease Control and Prevention’s Import Permit Program. We dedicate this work to our deceased colleagues Pablo Luna, Radislav Nakov, Bongani Kaimila, and Khean Lee Goh who passed away in recent years. The Hp GP was mainly supported by the Intramural Research Program from the US National Cancer Institute (NCI), National Institutes of Health (NIH). This work was supported in part by the intramural research programs of the US National Library of Medicine, the US National Institute on Minority Health and Health Disparities, and the US National Institute of Allergy and Infectious Diseases. The members of the bioinformatics group received support from the Swedish Society for Medical Research (K.T.), Assar Gabrielsson Foundation (K.T.), and Magnus Bergvall Foundation (K.T.). The collaborating centers for sample collection received grant support from the US NIH (P01CA116087, R01CA077955, R01DK058587 and P30DK058404 to R.M.P.; P01CA028842 and R01CA190612 to K.T.W.; P01CA028842, R01CA190612, K07CA125588, R03CA167773 and P30CA068485 to D.R.M.; K08CA252635 to R.J.H., K22CA226395 to M.G.-P.; and U54GM133807 to M.C.-C.), the German Federal Ministry of Education and Research (BMBF-0315905D, ERA-NET PathoGenoMics to P.M.), the French Association pour la Recherche Contre le Cancer (8412 to F.M.), the French Institut National du Cancer (07/3D1616/IABC-23-12/NC-NG and 2014-152 to F.M.), the Canceropole Grand Sud-Ouest (2010-08-canceropole GSO-Universite Bordeaux 2 to F.M.), the Japanese National Institutes of Health (DK62813 to Y.Y.), the Japanese Ministry of Education, Culture, Sports, Science, and Technology (18KK0266, 19H03473, 21H00346 and 22H02871 to Y.Y.), the National Fund for Innovation and Development of Science and Technology from the Ministry of Higher Education Science and Technology of the Dominican Republic (2012-2013-2A1-65 and 2015-3A1-182 to M.C.), the National Cancer Center of South Korea (2210630, I.J.C.), ArcticNet (RES0010178 to K.J.G.), the Network of Centres of Excellence of Canada, the Canadian Institutes for Health Research (MOP115031 to K.J.G.), Alberta Innovates Health Solutions (201201159 to K.J.G.), the University of Malaya-Ministry of Higher Education (UM.C/625/1/HIR/MOHE/CHAN-02 to J.V.), the Ministry of Science and Technology of Vietnam, the Kyrgyz State Medical Academy, the Italian Ministry of Health for Institutional Research, the Chilean National Fund for Health Research and Development (FONIS A19/0188, FONDECYT 1230504 and ANID-FONDAP 152220002 to A.R.; CONICYT-FONDAP 15130011 and FONDECYT 1231773 to A.H.C.), the Chilean Cancer Prevention and Control Center, the Horizon 2020 Programme of European Union (825832, “CeLac and European consortium for a personalized medicine approach to Gastric Cancer,” LEGACy, to T.F.-K. and A.R.), the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2014/26847-0, 2018/14267-2, 2018/02972-3 to E.D.-N.), the Departamento de Ciência e Tecnologia (DECIT), Ministry of Health, Brazil (PRONON, SIPAR 2500.035-167/2015-23 to E.D.-N.), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 314344/2020-9 to E.T.-S.), the Universidad de Costa Rica (742-B9-310 and 742-90912-19 to V.R.-M.), LABGIPAT (S.D.-B.), the Hospital Clínica Bíblica (C.C.-N.), the Greek Ministry of Culture and Education (InfeNeutra Project, NSRF 2007-2013, MIS450598, D.N.S.), the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, MIS5002486, D.N.S.), the Hellenic Helicobacter pylori Study Group (2012-2016, B.M.-G.), the Hellenic Society of Gastroenterology (National Multicenter Laboratory Surveillance Studies, 2018-2019, B.M.-G.), the Ministry of Science and Technology, Executive Yuan, Taiwan (109-2314-B-002-096; MOST 111-2314-B-002-012; MOST 109-2314-B-002-090-MY3 to J.-M.L. and M.-S.W.), the National Research Foundation of Singapore, the Singapore Ministry of Health’s National Medical Research Council (Open Fund-Large Collaborative Grant, MOH-OFLCG18May-0003), the University of Puerto Rico Comprehensive Cancer Center, the Fondo Nacional de Desarrollo Científico y Tecnológico (196-2015-FONDECYT to C.C.), Universidad Científica del Sur, and Instituto Nacional de Enfermedades Neoplasicas (INEN, Peru). The computations and data storage required for the analyses presented were enabled by resources in projects snic-2021/22-229 and snic-2021/23-234 provided by the National Academic Infrastructure for Supercomputing in Sweden (NAISS) and the Swedish National Infrastructure for Computing (SNIC) at the UPPMAX HPC, partially funded by the Swedish Research Council through grant agreements 2022-06725, and 2018-05973. The HpGP was mainly supported by the Intramural Research Program from the US National Cancer Institute (NCI), National Institutes of Health (NIH). This work was supported in part by the intramural research programs of the US National Library of Medicine, the US National Institute on Minority Health and Health Disparities, and the US National Institute of Allergy and Infectious Diseases. The members of the bioinformatics group received support from the Swedish Society for Medical Research (K.T.), Assar Gabrielsson Foundation (K.T.), and Magnus Bergvall Foundation (K.T.). The collaborating centers for sample collection received grant support from the US NIH (P01CA116087, R01CA077955, R01DK058587 and P30DK058404 to R.M.P.; P01CA028842 and R01CA190612 to K.T.W.; P01CA028842, R01CA190612, K07CA125588, R03CA167773 and P30CA068485 to D.R.M.; K08CA252635 to R.J.H., K22CA226395 to M.G.-P.; and U54GM133807 to M.C.-C.), the German Federal Ministry of Education and Research (BMBF-0315905D, ERA-NET PathoGenoMics to P.M.), the French Association pour la Recherche Contre le Cancer (8412 to F.M.), the French Institut National du Cancer (07/3D1616/IABC-23-12/NC-NG and 2014-152 to F.M.), the Canceropole Grand Sud-Ouest (2010-08-canceropole GSO-Universite Bordeaux 2 to F.M.), the Japanese National Institutes of Health (DK62813 to Y.Y.), the Japanese Ministry of Education, Culture, Sports, Science, and Technology (18KK0266, 19H03473, 21H00346 and 22H02871 to Y.Y.), the National Fund for Innovation and Development of Science and Technology from the Ministry of Higher Education Science and Technology of the Dominican Republic (2012-2013-2A1-65 and 2015-3A1-182 to M.C.), the National Cancer Center of South Korea (2210630, I.J.C.), ArcticNet (RES0010178 to K.J.G.), the Network of Centres of Excellence of Canada, the Canadian Institutes for Health Research (MOP115031 to K.J.G.), Alberta Innovates Health Solutions (201201159 to K.J.G.), the University of Malaya-Ministry of Higher Education (UM.C/625/1/HIR/MOHE/CHAN-02 to J.V.), the Ministry of Science and Technology of Vietnam, the Kyrgyz State Medical Academy, the Italian Ministry of Health for Institutional Research, the Chilean National Fund for Health Research and Development (FONIS A19/0188, FONDECYT 1230504 and ANID-FONDAP 152220002 to A.R.; CONICYT-FONDAP 15130011 and FONDECYT 1231773 to A.H.C.), the Chilean Cancer Prevention and Control Center, the Horizon 2020 Programme of European Union (825832, “CeLac and European consortium for a personalized medicine approach to Gastric Cancer,” LEGACy, to T.F.-K. and A.R.), the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2014/26847-0, 2018/14267-2, 2018/02972-3 to E.D.-N.), the Departamento de Ciência e Tecnologia (DECIT), Ministry of Health, Brazil (PRONON, SIPAR 2500.035-167/2015-23 to E.D.-N.), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 314344/2020-9 to E.T.-S.), the Universidad de Costa Rica (742-B9-310 and 742-90912-19 to V.R.-M.), LABGIPAT (S.D.-B.), the Hospital Clínica Bíblica (C.C.-N.), the Greek Ministry of Culture and Education (InfeNeutra Project, NSRF 2007-2013, MIS450598, D.N.S.), the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, MIS5002486, D.N.S.), the Hellenic Helicobacter pylori Study Group (2012-2016, B.M.-G.), the Hellenic Society of Gastroenterology (National Multicenter Laboratory Surveillance Studies, 2018-2019, B.M.-G.), the Ministry of Science and Technology, Executive Yuan, Taiwan (109-2314-B-002-096; MOST 111-2314-B-002-012; MOST 109-2314-B-002-090-MY3 to J.-M.L. and M.-S.W.), the National Research Foundation of Singapore, the Singapore Ministry of Health’s National Medical Research Council (Open Fund-Large Collaborative Grant, MOH-OFLCG18May-0003), the University of Puerto Rico Comprehensive Cancer Center, the Fondo Nacional de Desarrollo Científico y Tecnológico (196-2015-FONDECYT to C.C.), Universidad Científica del Sur, and Instituto Nacional de Enfermedades Neoplasicas (INEN, Peru). The computations and data storage required for the analyses presented were enabled by resources in projects snic-2021/22-229 and snic-2021/23-234 provided by the National Academic Infrastructure for Supercomputing in Sweden (NAISS) and the Swedish National Infrastructure for Computing (SNIC) at the UPPMAX HPC, partially funded by the Swedish Research Council through grant agreements 2022-06725, and 2018-05973.
| Funders | Funder number |
|---|---|
| CONICYT-FONDAP | 15130011, 1231773 |
| Chilean National Fund for Health Research and Development | |
| DECIT | |
| Departamento de Ciência e Tecnologia | |
| Division of Logistic Services | |
| FONIS | 1230504, A19/0188, ANID-FONDAP 152220002 |
| French Association pour la Recherche Contre le Cancer | 8412 |
| Greek Ministry of Culture and Education | MIS450598 |
| Hellenic Helicobacter pylori Study Group | |
| Horizon 2020 Programme of European Union | 825832 |
| Hospital Clínica Bíblica | |
| Instituto Nacional de Enfermedades Neoplasicas | snic-2021/22-229, snic-2021/23-234 |
| Japanese National Institutes of Health | DK62813 |
| Kyrgyz State Medical Academy | |
| Ministry of Health for Institutional Research | |
| Ministry of Higher Education Science and Technology of the Dominican Republic | 2015-3A1-182, 2012-2013-2A1-65 |
| Ministry of Science and Technology, Executive Yuan, Taiwan | 109-2314-B-002-090-MY3, MOST 111-2314-B-002-012, 109-2314-B-002-096 |
| National Cancer Center of South Korea | 2210630 |
| National Cancer Institute’s Division of Cancer Epidemiology | |
| National Fund for Innovation and Development of Science and Technology | |
| National Multicenter Laboratory Surveillance Studies | 2018-2019 |
| National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation | MIS5002486 |
| University of Malaya-Ministry of Higher Education | UM.C/625/1/HIR/MOHE/CHAN-02 |
| University of Puerto Rico Comprehensive Cancer Center | |
| National Institutes of Health | |
| National Cancer Institute | |
| National Institute of Allergy and Infectious Diseases | |
| U.S. National Library of Medicine | |
| National Institute on Minority Health and Health Disparities | |
| Ministry of Science and Technology | |
| Ministry of Health | 2500.035-167/2015-23 |
| Universidad Científica del Sur | |
| ArcticNet | RES0010178 |
| Canadian Institutes of Health Research | MOP115031 |
| Alberta Innovates - Health Solutions | 201201159 |
| National Medical Research Council | MOH-OFLCG18May-0003 |
| Ministry of Health -Singapore | |
| National Research Foundation Singapore | |
| Ministry of Education, Culture, Sports, Science and Technology | 18KK0266, 22H02871, 21H00346, 19H03473 |
| Fundação de Amparo à Pesquisa do Estado de São Paulo | 2018/02972-3, 2018/14267-2, 2014/26847-0 |
| Bundesministerium für Bildung und Forschung | BMBF-0315905D |
| Fondo Nacional de Desarrollo Científico y Tecnológico | 196-2015-FONDECYT |
| Conselho Nacional de Desenvolvimento Científico e Tecnológico | 314344/2020-9 |
| Svenska Sällskapet för Medicinsk Forskning | |
| Vetenskapsrådet | 2018-05973, 2022-06725 |
| AUTO21 Network of Centres of Excellence | |
| Stiftelsen Assar Gabrielssons Fond | |
| Universidad de Costa Rica | 742-90912-19, 742-B9-310 |
| Magnus Bergvalls Stiftelse | P01CA028842, K22CA226395, K07CA125588, P30DK058404, P30CA068485, R01CA077955, R03CA167773, U54GM133807, R01CA190612, P01CA116087, R01DK058587, K08CA252635 |
| Institut National du Cancer | 07/3D1616/IABC-23-12/NC-NG, 2014-152 |
| Cancéropôle Grand Ouest | |
| Hellenic Society of Gastroenterology |