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

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.

Outsourcing preparatory work based on a systematic literature review for the development of adverse outcome pathways (AOPs) relevant for the capacity of proteins to trigger celiac disease

“…The importance of the intestinal microbiota in CD is evident from several studies. The primary evidence indicates that the intestinal microbiota is altered in individuals with CD, with an increased or decreased presence of specific bacteria (Sánchez et al, 2013;D'Argenio et al, 2016;Olivares et al, 2018;El Mouzan et al, 2022;Xu et al, 2022;Aguayo-Patrón et al, 2023;González-García et al, 2023) or microorganismes (Giacomin et al, 2015). Some microorganisms may be also involved in the degradation of gluten peptides, thereby reducing their immunogenicity (Caminero et al, 2016;Herrán et al, 2017).…”