Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution

Abstract

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

Helicobacter pylori virulence factors and host genetic polymorphisms in a low gastric cancer incidence and high H pylori prevalence country

“…7 Last, the abundance of foods rich in antioxidant micronutrients consumed in Africa, as well as parts of Asia and Latin America, may also play a role in mitigating the development of GCA in susceptible populations. 27,28 In conclusion, we have demonstrated a virulent H pylori organism in the context of a susceptible South African human host, both of which impart a significant risk for untreated H pylori gastritis to drive the development of GCA. Given the high prevalence of infection and host polymorphisms, one must assume that other factors play a significant role in the development of GCA in our population.…”

“…26,27 Recent data also indicate that the immune response may be influenced by variability in human ancestry. 27,28 It may be that African ancestry represents co-evolution with H pylori, rather the European ancestry, which appears maladapted to chronic infection. 28 The archetypal hpAfrica2 strain which lacks the CagA pathogenicity island was not investigated in this study, however, CagA negative organism accounted for only one-third of the H pylori-positive samples in our study.…”

“…27,28 It may be that African ancestry represents co-evolution with H pylori, rather the European ancestry, which appears maladapted to chronic infection. 28 The archetypal hpAfrica2 strain which lacks the CagA pathogenicity island was not investigated in this study, however, CagA negative organism accounted for only one-third of the H pylori-positive samples in our study. 7 Last, the abundance of foods rich in antioxidant micronutrients consumed in Africa, as well as parts of Asia and Latin America, may also play a role in mitigating the development of GCA in susceptible populations.…”

“…Other potential factors playing a role in the low incidence of GCA may include a shift of the immune response to Helicobacte r infection towards a Th2 type response, on the basis of underlying chronic parasitic infection 26,27 . Recent data also indicate that the immune response may be influenced by variability in human ancestry 27,28 . It may be that African ancestry represents co‐evolution with H pylori, rather the European ancestry, which appears maladapted to chronic infection 28 .…”

<i>Helicobacter pylori</i>. The survival strategy of a commensal symbiont in the <i>Homo sapiens</i> population

“…[17,18]. Интересно, что из трех долгоживущих патогенов человека (H. py lori, Mycobacterium tuberculosis и вирус папилломы человека) H. py lo ri продемонстрировал лучшие эпидемиологические данные в пользу коэволюции [19]. Marshall B.…”