HLA-Haplotypes Influence Microbiota Structure in Northwestern Mexican Schoolchildren Predisposed for Celiac Disease or Type 1 Diabetes

Sandra V Aguayo-Patrón; Omar A Trujillo-Rivera; Fernanda Cornejo-Granados; Adrian Ochoa-Leyva; Ana M Calderón de la Barca

doi:10.3390/microorganisms11061412

HLA-Haplotypes Influence Microbiota Structure in Northwestern Mexican Schoolchildren Predisposed for Celiac Disease or Type 1 Diabetes

Microorganisms. 2023 May 27;11(6):1412. doi: 10.3390/microorganisms11061412.

Authors

Sandra V Aguayo-Patrón¹, Omar A Trujillo-Rivera¹, Fernanda Cornejo-Granados², Adrian Ochoa-Leyva², Ana M Calderón de la Barca¹

Affiliations

¹ Coordinación de Nutrición, Centro de Investigación en Alimentación y Desarrollo A.C., Hermosillo 83304, Mexico.
² Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de Mexico, Cuernavaca 62210, Mexico.

Abstract

To contribute to and elucidate the participation of microbiota in celiac disease (CD) and type 1 diabetes (T1D) development, we evaluated the influence of HLA haplotypes, familial risk, and diet on the microbiota of schoolchildren. We conducted a cross-sectional study on 821 apparently healthy schoolchildren, genotyping HLA DQ2/DQ8, and registering familial risk. We analyzed the fecal microbiota using 16S rRNA gene sequencing, and autoantibodies for CD or T1D by ELISA. After analyses, we created three groups: at-high-risk children (Group 1), at-high-risk children plus autoantibodies (Group 2), and nonrisk children (Group 3). HLA influenced the microbiota of Groups 1 and 2, decreasing phylogenetic diversity in comparison to Group 3. The relative abundance of Oscillospiraceae UCG_002, Parabacteroides, Akkermansia, and Alistipes was higher in Group 3 compared to Groups 1 and 2. Moreover, Oscillospiraceae UCG_002 and Parabacteroides were protectors of the autoantibodies' positivity (RRR = 0.441 and RRR = 0.034, respectively). Conversely, Agathobacter was higher in Group 2, and Lachnospiraceae was in both Groups 1 and 2. Lachnospiraceae correlated positively with the sucrose degradation pathway, while the principal genera in Group 3 were associated with amino acid biosynthesis pathways. In summary, HLA and familial risk influence microbiota composition and functionality in children predisposed to CD or T1D, increasing their autoimmunity risk.

Keywords: HLA DQ2 and DQ8; Northwestern Mexico; celiac disease; microbiota; schoolchildren; type 1 diabetes.

Grants and funding

O.A.T.R. and S.V.A.P. thank the National Council of Science and Technology (CONAHCYT) for the M.Sc., Ph.D., and postdoctoral scholarships. The Research Center for Food and Development depends on the Mexican National Council for Humanity, Science and Technology (CONAHCYT) for workers’ salaries and services.