Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig- or non-human primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H. suis in pigs possibly originates from non-human primates. Our data suggest that a host jump from macaques to pigs happened between 100 000 and 15 000 years ago and that pig domestication has had a significant impact on the spread of H. suis in the pig population, from where this pathogen occasionally infects humans. Thus, in contrast to our expectations, H. suis appears to have evolved in its main host in a completely different way than its close relative Helicobacter pylori in humans.

Animal Science Department Biomedical Primate Research Centre Rijswijk The Netherlands

Department of Biostatistics University of Oslo Oslo Norway

Department of Food Hygiene and Environmental Health Faculty of Veterinary Medicine University of Helsinki Helsinki Finland

Department of Laboratory Medicine Shinshu University Hospital Nagano Japan

Department of Mathematics and Statistics University of Helsinki Helsinki Finland

Department of Medical Biochemistry and Cell Biology University of Gothenburg Gothenburg Sweden

Department of Microbiology and Molecular Genetics University of California Davis CA USA

Department of Pathology Bacteriology and Avian Diseases Faculty of Veterinary Medicine Ghent University Ghent Belgium

Department of Veterinary Medicine Faculty of Veterinary Medicine University of Ibadan Ibadan Nigeria

Department of Veterinary Medicine University of Perugia Perugia Italy

Departments of Medicine and Microbiology and Immunology Center for Comparative Medicine University of California Davis CA USA

Faculty of Animal Science University of Agriculture and Forestry Hue University Hue City Vietnam

Kitasato Institute for Life Sciences and Graduate School of Control Sciences Kitasato University Tokyo Japan

Laboratory of Animal Pathology Department of Preventive Veterinary Medicine Universidade Estadual de Londrina Londrina Paraná Brazil

Laboratory of Experimental Medicine and Pediatrics University of Antwerp Antwerp Belgium

School of Biotechnology and Biomolecular Sciences University of New South Wales Sydney New South Wales Australia

School of Health Sciences Shinshu University School of Medicine Nagano Japan

School of Pharmaceutical Sciences Kitasato University Tokyo Japan

The State Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan China

University of Veterinary and Pharmaceutical Sciences Brno Faculty of Veterinary Hygiene and Ecology Department of Meat Hygiene and Technology Brno Czech Republic

Zoetis Kalamazoo MI USA

Zobrazit více v PubMed

Achtman M, Azuma T, Berg DE, Ito Y, Morelli G, Pan ZJ et al. (1999). Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol Microbiol 32: 459–470. PubMed

Baele M, Decostere A, Vandamme P, Ceelen L, Hellemans A, Mast J et al. (2008). Isolation and characterization of Helicobacter suis sp. nov. from pig stomachs. Int J Syst Evol Microbiol 58: 1350–1358. PubMed

Bassi P. (2013). Rilievi anatomo-patologici e batteriologici condotti sull’apparato gastroenterico di una metapopolazione di cinghiali (Sus scrofa, Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Morfofisiologia e patologia veterinaria con applicazioni biotecnologiche, 25 Ciclo, Dissertation thesis. doi: 10.6092/unibo/amsdottorato/5518. http://amsdottorato.unibo.it/5518/.

Blaecher C, Smet A, Flahou B, Pasmans F, Ducatelle R, Taylor D et al. (2013). Significantly higher frequency of Helicobacter suis in patients with idiopathic parkinsonism than in control patients. Aliment Pharmacol Ther 38: 1347–1353. PubMed PMC

Bosschem I, Flahou B, Bakker J, Heuvelman E, Langermans JAM, De Bruyne E et al. (2017). Comparative virulence of in vitro-cultured primate- and pig-associated Helicobacter suis strains in a BALB/c mouse and Mongolian gerbil model. Helicobacter 22: e12349. PubMed

Bosse M, Madsen O, Megens HJ, Frantz LA, Paudel Y, Crooijmans RP et al. (2014). Hybrid origin of European commercial pigs examined by an in-depth haplotype analysis on chromosome 1. Front Genet 5: 442. PubMed PMC

Cheng L, Connor TR, Siren J, Aanensen DM, Corander J. (2013). Hierarchical and spatially explicit clustering of DNA sequences with BAPS software. Mol Biol Evol 30: 1224–1228. PubMed PMC

Cucchi T, Hulme-Beaman A, Yuan J, Dobney K. (2011). Early Neolithic pig domestication at Jiahu, Henan Province, China: clues from molar shape analyses using geometric morphometric approaches. J Archaeol Sci 38: 11–22.

De Bruyne E, Flahou B, Chiers K, Meyns T, Kumar S, Vermoote M et al. (2012). An experimental Helicobacter suis infection causes gastritis and reduced daily weight gain in pigs. Vet Microbiol 160: 449–454. PubMed

De Cooman L, Flahou B, Houf K, Smet A, Ducatelle R, Pasmans F et al. (2013). Survival of Helicobacter suis bacteria in retail pig meat. Int J Food Microbiol 166: 164–167. PubMed

De Groote D, Ducatelle R, van Doorn L, Tilmant K, Verschuuren A, Haesebrouck F. (2000). Detection of "Candidatus Helicobacter suis" in gastric samples of pigs by PCR: comparison with other invasive diagnostic techniques. J Clin Microbiol 38: 1131–1135. PubMed PMC

Didelot X, Falush D. (2007). Inference of bacterial microevolution using multilocus sequence data. Genetics 175: 1251–1266. PubMed PMC

Drevon-Gaillot E, Perron-Lepage M-F, Clement C, Burnett R. (2006). A review of background findings in cynomolgus monkeys (Macaca fascicularis from three different geographical origins. Exp Toxicol Pathol 58: 77–88. PubMed

Drummond AJ, Rambaut A. (2007). BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7: 214. PubMed PMC

Dubois A, Tarnawski A, Newell DG, Fiala N, Dabros W, Stachura J et al. (1991). Gastric injury and invasion of parietal cells by spiral bacteria in rhesus monkeys. Are gastritis and hyperchlorhydria infectious diseases? Gastroenterology 100: 884–891. PubMed

Fabisiak M, Sapierzynski R, Salamaszynska-Guz A, Kizerwetter-Swida M. (2010). The first description of gastric Helicobacter in free-ranging wild boar (Sus scrofa from Poland. Pol J Vet Sci 13: 171–174. PubMed

Falush D, Wirth T, Linz B, Pritchard JK, Stephens M, Kidd M et al. (2003). Traces of human migrations in Helicobacter pylori populations. Science 299: 1582–1585. PubMed

Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T et al. (2003). How clonal is Staphylococcus aureus? J Bacteriol 185: 3307–3316. PubMed PMC

Foss D, Kopta L, Paquette J, Bowersock T, Choromanski L, Galvin J et al. (2013). Identification of Helicobacter suis in pig-producing regions of the United States. J Swine Health Prod 21: 242–247.

Frantz LA, Schraiber JG, Madsen O, Megens HJ, Cagan A, Bosse M et al. (2015). Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes. Nat Genet 47: 1141–1148. PubMed

Giuffra E, Kijas JMH, Amarger V, Carlborg O, Jeon JT, Andersson L et al. (2000). The origin of the domestic pig: independent domestication and subsequent introgression. Genetics 154: 1785–1791. PubMed PMC

Grasso G, Ripabelli G, Sammarco M, Ruberto A, Iannitto G. (1996). Prevalence of Helicobacter-like organisms in porcine gastric mucosa: a study of swine slaughtered in Italy. Comp Immunol Microbiol Infect Dis 19: 213–217. PubMed

Haesebrouck F, Pasmans F, Flahou B, Chiers K, Baele M, Meyns T et al. (2009). Gastric helicobacters in domestic animals and nonhuman primates and their significance for human health. Clin Microbiol Rev 22: 202–223. PubMed PMC

Hasegawa M, Kishino H, Yano TA. (1985). Dating of the human ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol 22: 160–174. PubMed

Hellemans A, Chiers K, Maes D, De Bock M, Decostere A, Haesebrouck F et al. (2007). Prevalence of 'Candidatus Helicobacter suis' in pigs of different ages. Vet Rec 161: 189–192. PubMed

Joosten M, Flahou B, Meyns T, Smet A, Arts J, De Cooman L et al. (2013). Case report: Helicobacter suis infection in a pig veterinarian. Helicobacter 18: 392–396. PubMed

Kanthaswamy S, Satkoski J, George D, Kou A, Erickson BJ-A, Smith DG et al. (2008). Hybridization and stratification of nuclear genetic variation in Macaca mulatta and M. fascicularis. Int J Primatol 29: 1295–1311. PubMed PMC

Kapusinszky B, Mulvaney U, Jasinska AJ, Deng X, Freimer N, Delwart E et al. (2015). Local virus extinctions following a host population bottleneck. J Virol 89: 8152–8161. PubMed PMC

Kodaman N, Pazos A, Schneider BG, Piazuelo MB, Mera R, Sobota RS et al. (2014). Human and Helicobacter pylori coevolution shapes the risk of gastric disease. Proc Natl Acad Sci USA 111: 1455–1460. PubMed PMC

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D et al. (2009). Circos: an information aesthetic for comparative genomics. Genome Res 19: 1639–1645. PubMed PMC

Kusters JG, van Vliet AHM, Kuipers EJ. (2006). Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19: 449–490. PubMed PMC

Larson G, Dobney K, Albarella U, Fang MY, Matisoo-Smith E, Robins J et al. (2005). Worldwide phylogeography of wild boar reveals multiple centers of pig domestication. Science 307: 1618–1621. PubMed

Larson G, Albarella U, Dobney K, Rowley-Conwy P, Schibler J, Tresset A et al. (2007). Ancient DNA, pig domestication, and the spread of the Neolithic into Europe. Proc Natl Acad Sci USA 104: 15276–15281. PubMed PMC

Larson G, Liu R, Zhao X, Yuan J, Fuller D, Barton L et al. (2010). Patterns of East Asian pig domestication, migration, and turnover revealed by modern and ancient DNA. Proc Natl Acad Sci USA 107: 7686–7691. PubMed PMC

Letunic I, Bork P. (2011). Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy. Nucleic Acids Res 39: W475–W478. PubMed PMC

Liang J, Ducatelle R, Pasmans F, Smet A, Haesebrouck F, Flahou B. (2013). Multilocus sequence typing of the porcine and human gastric pathogen Helicobacter suis. J Clin Microbiol 51: 920–926. PubMed PMC

Liang J, De Bruyne E, Ducatelle R, Smet A, Haesebrouck F, Flahou B. (2015). Purification of Helicobacter suis strains from biphasic cultures by single colony isolation: influence on strain characteristics. Helicobacter 20: 206–216. PubMed

Lindén S, Boren T, Dubois A, Carlstedt I. (2004). Rhesus monkey gastric mucins: oligomeric structure, glycoforms and Helicobacter pylori binding. Biochem J 379: 765–775. PubMed PMC

Martin M, Bhatnagar S, George M, Paster B, Canfield D, Eisen J et al. (2013). The impact of Helicobacter pylori infection on the gastric microbiota of the rhesus macaque. PLoS ONE 8: e76375. PubMed PMC

Matsui H, Takahashi T, Murayama SY, Uchiyama I, Yamaguchi K, Shigenobu S et al. (2014). Development of new PCR primers by comparative genomics for the detection of Helicobacter suis in gastric biopsy specimens. Helicobacter 19: 260–271. PubMed

Moodley Y, Linz B, Yamaoka Y, Windsor HM, Breurec S, Wu JY et al. (2009). The peopling of the Pacific from a bacterial perspective. Science 323: 527–530. PubMed PMC

Moodley Y, Linz B, Bond RP, Nieuwoudt M, Soodyall H, Schlebusch CM et al. (2012). Age of the association between Helicobacter pylori and Man. PLoS Pathog 8: e1002693. PubMed PMC

Morelli G, Didelot X, Kusecek B, Schwarz S, Bahlawane C, Falush D et al. (2010). Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families. PLoS Genet 6: e1001036. PubMed PMC

Nakamura M, Murayama SY, Serizawa H, Sekiya Y, Eguchi M, Takahashi S et al. (2007). ‘Candidatus Helicobacter heilmannii’ from a cynomolgus monkey induces gastric mucosa-associated lymphoid tissue lymphomas in C57BL/6 mice. Infect Immun 75: 1214–1222. PubMed PMC

O'Rourke J, Solnick J, Neilan B, Seidel K, Hayter R, Hansen L et al. (2004). Description of 'Candidatus Helicobacter heilmannii' based on DNA sequence analysis of 16 S rRNA and urease genes. Int J Syst Evol Microbiol 54: 2203–2211. PubMed

Park J, Seok S, Cho S, Baek M, Lee H, Kim D. (2004). The high prevalence of Helicobacter sp. in porcine pyloric mucosa and its histopathological and molecular characteristics. Vet Microbiol 104: 219–225. PubMed

Queiroz DMD, Rocha GA, Mendes EN, deMoura SB, deOliveira AMR, Miranda D. (1996). Association between Helicobacter and gastric ulcer disease of the pars esophagea in swine. Gastroenterology 111: 19–27. PubMed

Smith EM, Needs PF, Manley G, Green LE. (2014). Global distribution and diversity of ovine-associated Staphylococcus aureus. Infect Genet Evol 22: 208–215. PubMed PMC

Solnick JV, Chang K, Canfield DR, Parsonnet J. (2003). Natural acquisition of Helicobacter pylori infection in newborn rhesus Macaques. J Clin Microbiol 41: 5511–5516. PubMed PMC

Stolte M, Kroher G, Meining A, Morgner A, Bayerdörffer E, Bethke B. (1997). Comparison of Helicobacter pylori and H. heilmannii gastritis. A matched control study involving 404 patients. Scand J Gastroenterol 32: 28–33. PubMed

Szeredi L, Palkovics G, Solymosi N, Tekes L, Mehesfalvi J. (2005). Study on the role of gastric Helicobacter infection in gross pathological and histological lesions of the stomach in finishing pigs. Acta Vet Hung 53: 371–383. PubMed

Tamura K, Nei M, Kumar S. (2004). Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA 101: 11030–11035. PubMed PMC

Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. (2013). MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Mol Biol Evol 30: 2725–2729. PubMed PMC

Tosi AJ, Morales JC, Melnick DJ. (2002). Y-chromosome and mitochondrial markers in Macaca fascicularis indicate introgression with Indochinese M. mulatta and a biogeographic barrier in the Isthmus of Kra. Int J Primatol 23: 161–178.

Trewby H, Ayele G, Borzacchiello G, Brandt S, Campo MS, Del Fava C et al. (2014). Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure. J Gen Virol 95: 2748–2756. PubMed PMC

Van den Bulck K, Decostere A, Baele M, Driessen A, Debongnie JC, Burette A et al. (2005). Identification of non-Helicobacter pylori spiral organisms in gastric samples from humans, dogs, and cats. J Clin Microbiol 43: 2256–2260. PubMed PMC

Zanoni RG, Piva S, Florio D, Bassi P, Mion D, Cnockaert M et al. (2016). Helicobacter apri sp. nov., isolated from wild boars. Int J Syst Evol Microbiol 66: 2876–2882. PubMed