PMID- 31370803 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20231013 IS - 1528-3658 (Electronic) IS - 1076-1551 (Print) IS - 1076-1551 (Linking) VI - 25 IP - 1 DP - 2019 Aug 1 TI - Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus. PG - 35 LID - 10.1186/s10020-019-0102-5 [doi] LID - 35 AB - OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved. METHODS: Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR). RESULTS: The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes. CONCLUSIONS: SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice. FAU - Ma, Yiyangzi AU - Ma Y AD - NHC Key Laboratory of Human Disease Comparative Medicine, The Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing, China. FAU - Xu, Xiaoxue AU - Xu X AD - Department of Core Facility Center, Capital Medical University, Beijing, China. FAU - Li, Mengtao AU - Li M AD - Division of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Cai, Jun AU - Cai J AD - Hypertension Center, Fuwai hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Disease of China, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. caijun7879@126.com. FAU - Wei, Qiang AU - Wei Q AD - NHC Key Laboratory of Human Disease Comparative Medicine, The Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing, China. weiqiang0430@cnilas.org. FAU - Niu, Haitao AU - Niu H AUID- ORCID: 0000-0003-2210-2051 AD - NHC Key Laboratory of Human Disease Comparative Medicine, The Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing, China. niuhaitao@cnilas.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190801 PL - England TA - Mol Med JT - Molecular medicine (Cambridge, Mass.) JID - 9501023 SB - IM MH - Animals MH - Enzyme-Linked Immunosorbent Assay MH - Fecal Microbiota Transplantation MH - Feces/*microbiology MH - Female MH - Gastrointestinal Microbiome/*physiology MH - High-Throughput Nucleotide Sequencing MH - Inflammation/*microbiology MH - Lupus Erythematosus, Systemic/*immunology/*microbiology MH - Mice MH - Mice, Inbred C57BL MH - Microbiota/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC6676588 OTO - NOTNLM OT - Fecal microbiota transplantation2 OT - Gut microbiota1 OT - Immune response4 OT - Lupus susceptibility gene5 OT - Systemic lupus erythematosus3 COIS- The authors declare that they have no competing interests. EDAT- 2019/08/03 06:00 MHDA- 2020/06/23 06:00 PMCR- 2019/08/01 CRDT- 2019/08/03 06:00 PHST- 2019/04/06 00:00 [received] PHST- 2019/06/25 00:00 [accepted] PHST- 2019/08/03 06:00 [entrez] PHST- 2019/08/03 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/08/01 00:00 [pmc-release] AID - 10.1186/s10020-019-0102-5 [pii] AID - 102 [pii] AID - 10.1186/s10020-019-0102-5 [doi] PST - epublish SO - Mol Med. 2019 Aug 1;25(1):35. doi: 10.1186/s10020-019-0102-5.