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

• Published in: Microorganisms (Basel) Vol. 11; no. 6; p. 1412
• Main Authors: Aguayo-Patrón, Sandra V, Trujillo-Rivera, Omar A, Cornejo-Granados, Fernanda, Ochoa-Leyva, Adrian, Calderón de la Barca, Ana M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-05-2023; MDPI
• Subjects: Amino acid composition; Amino acids; Antibiotics; Antibodies; At risk youth; Autoantibodies; Autoimmune diseases; Autoimmunity; Biosynthesis; Breastfeeding & lactation; Celiac disease; Children; Children & youth; Diabetes mellitus (insulin dependent); Diet; Disease; Elementary school students; Enzyme-linked immunosorbent assay; Families & family life; Fecal microflora; Gene sequencing; Genetic aspects; Genotyping; Guardians; Haplotypes; Health aspects; Health care; Health risk assessment; Histocompatibility antigen HLA; Histocompatibility antigens; HLA DQ2 and DQ8; HLA histocompatibility antigens; Lachnospiraceae; Metabolism; Metabolites; Methods; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Northwestern Mexico; Parabacteroides; Phylogeny; Physiological aspects; Relative abundance; Risk analysis; Risk factors; RNA sequencing; rRNA 16S; schoolchildren; Sucrose; Taxonomy; Type 1 diabetes; Mexico; United States > US; microbiota; schoolchildren; celiac disease; type 1 diabetes; Northwestern Mexico; HLA DQ2 and DQ8
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms11061412

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,
,
, and
was higher in Group 3 compared to Groups 1 and 2. Moreover, Oscillospiraceae UCG_002 and
were protectors of the autoantibodies' positivity (RRR = 0.441 and RRR = 0.034, respectively). Conversely,
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.