Ancient pathogen-driven adaptation triggers increased susceptibility to nonceliac wheat sensitivity in present-day European populations

Marco Sazzini, Sara De Fanti, Anna Cherubini, Andrea Quagliariello, Giuseppe Profiti, Pier Luigi Martelli, Rita Casadio, Chiara Ricci, Massimo Campieri, Alberto Lanzini, Umberto Volta, Giacomo Caio, Claudio Franceschi, Enzo Spisni, Donata Luiselli

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Non-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones. Methods: To explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci. Results: Our results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression. Conclusions: This led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies.

Original languageEnglish
JournalGenes and Nutrition
Volume11
Issue number1
DOIs
Publication statusPublished - 2016

Fingerprint

Triticum
Haplotypes
Population
Genetic Selection
Chemokines
Alleles
Gliadin
High-Throughput Nucleotide Sequencing
Anthropology
Homozygote
Epidemiology
Diet
Inflammation
Genes

Keywords

  • Evolutionary medicine
  • Human adaptation
  • Human dietary shifts
  • Natural selection
  • Non-celiac wheat sensitivity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Genetics

Cite this

Ancient pathogen-driven adaptation triggers increased susceptibility to nonceliac wheat sensitivity in present-day European populations. / Sazzini, Marco; De Fanti, Sara; Cherubini, Anna; Quagliariello, Andrea; Profiti, Giuseppe; Martelli, Pier Luigi; Casadio, Rita; Ricci, Chiara; Campieri, Massimo; Lanzini, Alberto; Volta, Umberto; Caio, Giacomo; Franceschi, Claudio; Spisni, Enzo; Luiselli, Donata.

In: Genes and Nutrition, Vol. 11, No. 1, 2016.

Research output: Contribution to journalArticle

Sazzini, M, De Fanti, S, Cherubini, A, Quagliariello, A, Profiti, G, Martelli, PL, Casadio, R, Ricci, C, Campieri, M, Lanzini, A, Volta, U, Caio, G, Franceschi, C, Spisni, E & Luiselli, D 2016, 'Ancient pathogen-driven adaptation triggers increased susceptibility to nonceliac wheat sensitivity in present-day European populations', Genes and Nutrition, vol. 11, no. 1. https://doi.org/10.1186/s12263-016-0532-4
Sazzini, Marco ; De Fanti, Sara ; Cherubini, Anna ; Quagliariello, Andrea ; Profiti, Giuseppe ; Martelli, Pier Luigi ; Casadio, Rita ; Ricci, Chiara ; Campieri, Massimo ; Lanzini, Alberto ; Volta, Umberto ; Caio, Giacomo ; Franceschi, Claudio ; Spisni, Enzo ; Luiselli, Donata. / Ancient pathogen-driven adaptation triggers increased susceptibility to nonceliac wheat sensitivity in present-day European populations. In: Genes and Nutrition. 2016 ; Vol. 11, No. 1.
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AU - De Fanti, Sara

AU - Cherubini, Anna

AU - Quagliariello, Andrea

AU - Profiti, Giuseppe

AU - Martelli, Pier Luigi

AU - Casadio, Rita

AU - Ricci, Chiara

AU - Campieri, Massimo

AU - Lanzini, Alberto

AU - Volta, Umberto

AU - Caio, Giacomo

AU - Franceschi, Claudio

AU - Spisni, Enzo

AU - Luiselli, Donata

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AB - Background: Non-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones. Methods: To explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci. Results: Our results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression. Conclusions: This led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies.

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