Bei-di Chen1, Xin-Miao Jia1, Jia-Yue Xu2, Li-Dan Zhao1, Jun-Yi Ji3, Bing-Xuan Wu1, Yue Ma2, Hao Li4, Xiao-Xia Zuo5, Wen-You Pan6, Xiao-Han Wang7, Shuang Ye8, George C Tsokos4, Jun Wang2, Xuan Zhang1. 1. Department of Rheumatology, Clinical Immunology Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, and Peking Union Medical College, Beijing, China. 2. Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China. 3. Tsinghua University, Beijing, China. 4. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. 5. Xiangya Hospital and Central South University, Changsha, China. 6. Huaian First People's Hospital and Nanjing Medical University, Huaian, China. 7. Anyang District Hospital, Anyang, China. 8. Renji Hospital and Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract
OBJECTIVE: Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. METHODS: Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides. RESULTS: Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species. CONCLUSION: This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.
OBJECTIVE: Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. METHODS: Fecal metagenomes from 117 patients with untreated SLE and 52 SLEpatients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLEpatients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides. RESULTS: Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLEpatients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLEpatients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species. CONCLUSION: This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.
Authors: Huan Zhao; Bing Han; Xuan Li; Chengtao Sun; Yufei Zhai; Man Li; Mi Jiang; Weiping Zhang; Yi Liang; Guoyin Kai Journal: Front Pharmacol Date: 2022-05-05 Impact factor: 5.988
Authors: Harini Bagavant; Antonina M Araszkiewicz; Jessica K Ingram; Katarzyna Cizio; Joan T Merrill; Cristina Arriens; Joel M Guthridge; Judith A James; Umesh S Deshmukh Journal: Front Immunol Date: 2021-05-28 Impact factor: 7.561