Human and Helicobacter pylori coevolution shapes the risk of gastric disease.
Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster predominating in a low-risk, coastal population and a European cluster in a high-risk, mountain population. The human ancestry of the biopsied individuals also varied with geography, with mostly African ancestry in the coastal region (58%), and mostly Amerindian ancestry in the mountain region (67%). The interaction between the host and pathogen ancestries completely accounted for the difference in the severity of gastric lesions in the two regions of Colombia. In particular, African H. pylori ancestry was relatively benign in humans of African ancestry but was deleterious in individuals with substantial Amerindian ancestry. Thus, coevolution likely modulated disease risk, and the disruption of coevolved human and H. pylori genomes can explain the high incidence of gastric disease in the mountain population.
Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Divisions of Gastroenterology and Infectious Diseases, Department of Medicine, and Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
Nuri
N
Kodaman
Alvaro
A
Pazos
Barbara G
BG
Schneider
M Blanca
MB
Piazuelo
Robertino
R
Mera
Rafal S
RS
Sobota
Liviu A
LA
Sicinschi
Carrie L
CL
Shaffer
Judith
J
Romero-Gallo
Thibaut
T
de Sablet
Reed H
RH
Harder
Luis E
LE
Bravo
Richard M
RM
Peek
Keith T
KT
Wilson
Timothy L
TL
Cover
Scott M
SM
Williams
Pelayo
P
Correa
D000328:Adult; D000368:Aged; D004198:Disease Susceptibility; D019143:Evolution, Molecular; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D013272:Stomach Diseases / Q000382:microbiology*
Latin America; admixture; histopathology; inflammation