Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia

Colonization by Helicobacter pylori of leprosy patients in Spain: immunomodulation to low molecular weight antigens of H. pylori

We studied the prevalence of Helicobacter pylori in patients with leprosy and the effects of co-infection on the immune response to Helicobacter antigens in the polar groups of leprosy (lepromatous and tuberculoid). We showed that there is no difference in the prevalence of H. pylori in patients with leprosy as compared to a non-leprosy population. We also demonstrated that the immune response to low molecular weight H. pylori antigens (35, 26 and 19 kDa) differs in patients with lepromatous as compared to those with tuberculoid leprosy. In lepromatous leprosy, we show that there is a higher prevalence of the 35 and 26 kDa antigens, but a lower prevalence of the 19 kDa antigen. These immunological results are consistent with previous histopathological studies illustrating a more severe gastrointestinal inflammation in lepromatous patients; importantly, a response to the 35 kDa antigen is recognized as a marker for the development of ulcerative disease

Helicobacter pylori Infection in Thailand: A Nationwide Study of the CagA Phenotype

The risk to develop gastric cancer in Thailand is relatively low among Asian countries. In addition, the age-standardized incidence rate (ASR) of gastric cancer in Thailand varies with geographical distribution; the ASR in the North region is 3.5 times higher than that in the South region. We hypothesized that the prevalence of H. pylori infection and diversity of CagA phenotype contributes to the variety of gastric cancer risk in various regions of Thailand.We conducted a nationwide survey within Thailand. We determined H. pylori infection prevalence by detecting H. pylori, using histochemical and immunohistochemical methods. The anti-CagA antibody and anti-East-Asian type CagA antibody (α-EAS Ab), which showed high accuracy in several East Asian countries, were used to determine CagA phenotype.Among 1,546 patients from four regions, including 17 provinces, the overall prevalence of H. pylori infection was 45.9% (710/1,546). Mirroring the prevalence of H. pylori infection, histological scores were the lowest in the South region. Of the 710 H. pylori-positive patients, 93.2% (662) were immunoreactive with the anti-CagA antibody. CagA-negative strain prevalence in the South region was significantly higher than that in other regions (17.9%; 5/28; p < 0.05). Overall, only 77 patients (11.6%) were immunoreactive with the α-EAS Ab. There were no differences in the α-EAS Ab immunoreactive rate across geographical regions.This is the first study using immunohistochemistry to confirm H. pylori infections across different regions in Thailand. The prevalence of East-Asian type CagA H. pylori in Thailand was low. The low incidence of gastric cancer in Thailand may be attributed to the low prevalence of precancerous lesions. The low incidence of gastric cancer in the South region might be associated with the lower prevalence of H. pylori infection, precancerous lesions, and CagA-positive H. pylori strains, compared with that in the other regions

Prevalence, risk factors, and virulence genes of Helicobacter pylori among dyspeptic patients in two different gastric cancer risk regions of Thailand

Gastric cancer risk is varied among different regions of Thailand. We examined the characteristics of Helicobacter pylori infection in two regions of Thailand. The H. pylori status of 273 dyspeptic patients (136 from the South and 137 from the North; a low and high incidence of gastric cancer region, respectively) was evaluated, and virulence genotypes (cagA, vacA, hrgA and jhp0562-positive/β-(1,3)galT) were determined. The overall H. pylori infection rate was 34.1% (93/273). The prevalence was higher in the North than in the South (50.4% vs. 17.6%, P <0.001) and was significantly higher among individuals with the following characteristics: low income, birthplace in the Northeast or North regions, agricultural employment, or consumption of alcohol or unboiling water. Among these socio-demographic determinants, region was an independent risk factor for H. pylori infection (odds ratio = 6.37). Patients including both H. pylori infected and uninfected cases who lived in the North had significantly more severe histological scores than those in the South. In contrast, among H. pylori-positive cases, patients in the South had significantly more severe histological scores than those in the North. Of the 74 strains cultured, 56.8% carried Western-type cagA, with a higher proportion in the South than in the North (76.2% vs. 49.1%, P = 0.05). In disagreement with the current consensus, patients infected with the Western-type cagA strains had more severe inflammation scores in the antrum than those infected with the East Asian-type cagA strains (P = 0.027). Moreover, Western-type cagA strains induced more severe histological scores in patients from the South than those of either genotype from the North. Other virulence genes had no influence on histological scores. The incidence of gastric cancer in Thailand was different among regions and corresponded to differences in the prevalence of H. pylori infection. More careful follow-up for patients in the South will be required, even if they are infected with H. pylori carrying Western-type cagA