PMID- 36203614 OWN - NLM STAT- MEDLINE DCOM- 20221010 LR - 20221012 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Disease predisposition of human leukocyte antigen class II genes influences the gut microbiota composition in patients with primary biliary cholangitis. PG - 984697 LID - 10.3389/fimmu.2022.984697 [doi] LID - 984697 AB - BACKGROUND: The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown. METHODS: A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing. RESULTS: Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni's correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients' gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P<0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients (P<0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative. CONCLUSION: The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis. CI - Copyright (c) 2022 Huang, Zhang, Han, Zhao, Liao, Ma, Xu, Li, Han, Liu, Wang, Lou, Zhang, Zhao, Li, Liu and Yan. FAU - Huang, Chun-Yang AU - Huang CY AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Hai-Ping AU - Zhang HP AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Han, Wei-Jia AU - Han WJ AD - Department of Gastroenterology, Integrated Clinical Microecology Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China. FAU - Zhao, Dan-Tong AU - Zhao DT AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Liao, Hui-Yu AU - Liao HY AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Ma, Yin-Xue AU - Ma YX AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Xu, Bin AU - Xu B AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Li, Li-Juan AU - Li LJ AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Han, Ying AU - Han Y AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Liu, Xiu-Hong AU - Liu XH AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Wang, Qi AU - Wang Q AD - Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Lou, Jin-Li AU - Lou JL AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Xiao-Dan AU - Zhang XD AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Zhao, Juan AU - Zhao J AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Li, Wen-Juan AU - Li WJ AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Liu, Yan-Min AU - Liu YM AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. FAU - Yan, Hui-Ping AU - Yan HP AD - Second Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China. AD - Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220920 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA Antigens) RN - 0 (HLA-DRB1 Chains) RN - 63231-63-0 (RNA) SB - IM MH - Female MH - *Gastrointestinal Microbiome/genetics MH - Genes, MHC Class II MH - HLA Antigens/genetics MH - HLA-DRB1 Chains/genetics MH - Humans MH - *Liver Cirrhosis, Biliary/genetics MH - Male MH - RNA PMC - PMC9531677 OTO - NOTNLM OT - bioinformatic analysis OT - gut microbiota OT - human leukocyte antigen OT - primary biliary cholangitis OT - susceptibility gene COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JJ declared a shared parent affiliation with the authors C-YH, H-PZ, D-TZ, H-YL, Y-XM, BX, L-JL, YH, X-HL, QW, J-LL, X-DZ, JZ, W-JL, Y-ML, and H-PY to the handling editor at the time of review. EDAT- 2022/10/08 06:00 MHDA- 2022/10/12 06:00 PMCR- 2022/01/01 CRDT- 2022/10/07 02:37 PHST- 2022/07/02 00:00 [received] PHST- 2022/08/11 00:00 [accepted] PHST- 2022/10/07 02:37 [entrez] PHST- 2022/10/08 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.984697 [doi] PST - epublish SO - Front Immunol. 2022 Sep 20;13:984697. doi: 10.3389/fimmu.2022.984697. eCollection 2022.