PMID- 36582242 OWN - NLM STAT- MEDLINE DCOM- 20230102 LR - 20230117 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - High-risk genotypes for type 1 diabetes are associated with the imbalance of gut microbiome and serum metabolites. PG - 1033393 LID - 10.3389/fimmu.2022.1033393 [doi] LID - 1033393 AB - BACKGROUND: The profile of gut microbiota, serum metabolites, and lipids of type 1 diabetes (T1D) patients with different human leukocyte antigen (HLA) genotypes remains unknown. We aimed to explore gut microbiota, serum metabolites, and lipids signatures in individuals with T1D typed by HLA genotypes. METHODS: We did a cross-sectional study that included 73 T1D adult patients. Patients were categorized into two groups according to the HLA haplotypes they carried: those with any two of three susceptibility haplotypes (DR3, DR4, DR9) and without any of the protective haplotypes (DR8, DR11, DR12, DR15, DR16) were defined as high-risk HLA genotypes group (HR, n=30); those with just one or without susceptibility haplotypes as the non-high-risk HLA genotypes group (NHR, n=43). We characterized the gut microbiome profile with 16S rRNA gene amplicon sequencing and analyzed serum metabolites with liquid chromatography-mass spectrometry. RESULTS: Study individuals were 32.5 (8.18) years old, and 60.3% were female. Compared to NHR, the gut microbiota of HR patients were characterized by elevated abundances of Prevotella copri and lowered abundances of Parabacteroides distasonis. Differential serum metabolites (hypoxanthine, inosine, and guanine) which increased in HR were involved in purine metabolism. Different lipids, phosphatidylcholines and phosphatidylethanolamines, decreased in HR group. Notably, Parabacteroides distasonis was negatively associated (p