{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:56:07Z","timestamp":1791410167551,"version":"4.3.3"},"reference-count":40,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Type 1 and type 2 diabetes are associated with gut dysbiosis. However, the relationship between the gut microbiota and latent autoimmune diabetes in adults (LADA), sharing clinical and metabolic features with classic type 1 and type 2 diabetes, remains unclear. Here, we used a multiomics approach to identify the characteristics of the gut microbiota and metabolic profiles in patients with LADA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>This age- and sex-matched case-control study included 30 patients with LADA, 29 patients with classic type 1 diabetes, 31 patients with type 2 diabetes, and 29 healthy individuals. The gut microbiota profiles were identified through the 16S rRNA gene, and fecal and serum metabolites were measured through untargeted liquid chromatography-mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Patients with LADA had a significantly different structure and composition of the gut microbiota and their metabolites as well as a severe deficiency of short-chain fatty acid\u2013producing bacteria. The gut microbiota structure of the patients with LADA was more similar to that of patients with type 1 diabetes who were positive for GAD antibody. We identified seven serum metabolite modules and eight fecal metabolite modules that differed between the LADA group and the other groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The characteristic gut microbiota and related metabolites of patients with LADA are associated with autoantibodies, glucose metabolism, islet function, and inflammatory factors, which may contribute to the pathogenesis of LADA. Future longitudinal studies should explore whether modulating the gut microbiota and related metabolites can alter the natural course of autoimmune diabetes in the quest for new therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc20-2975","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T16:40:11Z","timestamp":1633624811000},"page":"2738-2746","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":48,"title":["Characteristics of the Gut Microbiota and Metabolism in Patients With Latent Autoimmune Diabetes in Adults: A Case-Control Study"],"prefix":"10.2337","volume":"44","author":[{"given":"Yuanyuan","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongcai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of People\u2019s Hospital of Zhengzhou University, Henan Provincial People\u2019s Hospital, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Adfontes (Shanghai) Biotechnology Co., Ltd., Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-0994","authenticated-orcid":false,"given":"Huijuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"2022031309333541500_B1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12916-017-0846-0","article-title":"Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes","volume":"15","author":"Mishra","year":"2017","journal-title":"BMC Med"},{"key":"2022031309333541500_B2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2337\/db12-0207","article-title":"Frequency, immunogenetics, and clinical characteristics of latent autoimmune diabetes in China (LADA China study): a nationwide, multicenter, clinic-based cross-sectional study","volume":"62","author":"Zhou","year":"2013","journal-title":"Diabetes"},{"key":"2022031309333541500_B3","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1111\/dme.12700","article-title":"Corrigendum. Danish Diabetes Academy Workshop and Workshop Speakers. Latent autoimmune diabetes of the adult: current knowledge and uncertainty","volume":"32","author":"Laugesen","year":"2015","journal-title":"Diabet Med"},{"key":"2022031309333541500_B4","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrendo.2017.99","article-title":"Adult-onset autoimmune diabetes: current knowledge and implications for management","volume":"13","author":"Buzzetti","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"2022031309333541500_B5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00592-011-0333-6","article-title":"Gut microbiota and diabetes: from pathogenesis to therapeutic perspective","volume":"48","author":"Burcelin","year":"2011","journal-title":"Acta Diabetol"},{"key":"2022031309333541500_B6","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.1223813","article-title":"Host-gut microbiota metabolic interactions","volume":"336","author":"Nicholson","year":"2012","journal-title":"Science"},{"key":"2022031309333541500_B7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nature13279","article-title":"Focused specificity of intestinal TH17 cells towards commensal bacterial antigens","volume":"510","author":"Yang","year":"2014","journal-title":"Nature"},{"key":"2022031309333541500_B8","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nrendo.2015.218","article-title":"The role of the intestinal microbiota in type 1 diabetes mellitus","volume":"12","author":"Knip","year":"2016","journal-title":"Nat Rev Endocrinol"},{"key":"2022031309333541500_B9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41575-019-0242-7","article-title":"Microbiota in pancreatic health and disease: the next frontier in microbiome research","volume":"17","author":"Thomas","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2022031309333541500_B10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.tifs.2016.08.009","article-title":"Interplay between gut microbiota, its metabolites and human metabolism: dissecting cause from consequence","volume":"57","author":"Hartstra","year":"2016","journal-title":"Trends Food Sci Technol"},{"key":"2022031309333541500_B11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The intestinal microbiota fuelling metabolic inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2022031309333541500_B12","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.3389\/fimmu.2017.01882","article-title":"Gut microbiota dysbiosis drives and implies novel therapeutic strategies for diabetes mellitus and related metabolic diseases","volume":"8","author":"Li","year":"2017","journal-title":"Front Immunol"},{"key":"2022031309333541500_B13","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S","article-title":"Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation","volume":"15","author":"Alberti","year":"1998","journal-title":"Diabet Med"},{"key":"2022031309333541500_B14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.2337\/dc08-1419","article-title":"Metabolic syndrome and autoimmune diabetes: Action LADA 3","volume":"32","author":"Hawa","year":"2009","journal-title":"Diabetes Care"},{"key":"2022031309333541500_B15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/dmrr.2396","article-title":"Zinc transporter 8 autoantibody (ZnT8A) could help differentiate latent autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetes mellitus","volume":"29","author":"Huang","year":"2013","journal-title":"Diabetes Metab Res Rev"},{"key":"2022031309333541500_B16","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/dmrr.2779","article-title":"Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up","volume":"32","author":"Huang","year":"2016","journal-title":"Diabetes Metab Res Rev"},{"key":"2022031309333541500_B17","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/nar\/gks808","article-title":"Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies","volume":"41","author":"Klindworth","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2022031309333541500_B18","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2022031309333541500_B19","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods"},{"key":"2022031309333541500_B20","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1093\/bioinformatics\/bts252","article-title":"SINA: accurate high-throughput multiple sequence alignment of ribosomal RNA genes","volume":"28","author":"Pruesse","year":"2012","journal-title":"Bioinformatics"},{"key":"2022031309333541500_B21","doi-asserted-by":"crossref","first-page":"e1005752","DOI":"10.1371\/journal.pcbi.1005752","article-title":"mixOmics: an R package for \u2019omics feature selection and multiple data integration","volume":"13","author":"Rohart","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"2022031309333541500_B22","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2022031309333541500_B23","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/s41380-018-0047-z","article-title":"Polyunsaturated fatty acids metabolism, purine metabolism and inosine as potential independent diagnostic biomarkers for major depressive disorder in children and adolescents","volume":"24","author":"Zhou","year":"2019","journal-title":"Mol Psychiatry"},{"key":"2022031309333541500_B24","doi-asserted-by":"crossref","first-page":"i11","DOI":"10.18637\/jss.v046.i11","article-title":"Fast R functions for robust correlations and hierarchical clustering","volume":"46","author":"Langfelder","year":"2012","journal-title":"J Stat Softw"},{"key":"2022031309333541500_B25","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/bioinformatics\/btm563","article-title":"Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut package for R","volume":"24","author":"Langfelder","year":"2008","journal-title":"Bioinformatics"},{"key":"2022031309333541500_B26","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/sim.4780090710","article-title":"More powerful procedures for multiple significance testing","volume":"9","author":"Hochberg","year":"1990","journal-title":"Stat Med"},{"key":"2022031309333541500_B27","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/cmi.2017.57","article-title":"Microbiota or short-chain fatty acids: which regulates diabetes?","volume":"15","author":"Kim","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"2022031309333541500_B28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut microbial metabolites in obesity, NAFLD and T2DM","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"2022031309333541500_B29","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/ni.3730","article-title":"Dietary short-chain fatty acids protect against type 1 diabetes","volume":"18","author":"Wen","year":"2017","journal-title":"Nat Immunol"},{"key":"2022031309333541500_B30","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cmet.2020.06.011","article-title":"The gut microbiota in prediabetes and diabetes: a population-based cross-sectional study","volume":"32","author":"Wu","year":"2020","journal-title":"Cell Metab"},{"key":"2022031309333541500_B31","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41574-019-0254-y","article-title":"The heterogeneous pathogenesis of type 1 diabetes mellitus","volume":"15","author":"Ilonen","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"2022031309333541500_B32","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/ni.3713","article-title":"Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes","volume":"18","author":"Mari\u00f1o","year":"2017","journal-title":"Nat Immunol"},{"key":"2022031309333541500_B33","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2337\/dc06-1696","article-title":"High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes","volume":"30","author":"Buzzetti","year":"2007","journal-title":"Diabetes Care"},{"key":"2022031309333541500_B34","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2337\/dc12-0931","article-title":"Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7","volume":"36","author":"Hawa","year":"2013","journal-title":"Diabetes Care"},{"key":"2022031309333541500_B35","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metab"},{"key":"2022031309333541500_B36","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1093\/ije\/dyw143","article-title":"Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes","volume":"45","author":"Zheng","year":"2016","journal-title":"Int J Epidemiol"},{"key":"2022031309333541500_B37","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1017\/S0007114517001568","article-title":"Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women\u2019s Health Initiative","volume":"117","author":"Isanejad","year":"2017","journal-title":"Br J Nutr"},{"key":"2022031309333541500_B38","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.2337\/db07-0123","article-title":"Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms","volume":"56","author":"Zhang","year":"2007","journal-title":"Diabetes"},{"key":"2022031309333541500_B39","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1113\/JP275075","article-title":"Restoration of metabolic health by decreased consumption of branched-chain amino acids","volume":"596","author":"Cummings","year":"2018","journal-title":"J Physiol"},{"key":"2022031309333541500_B40","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3390\/nu8070405","article-title":"The Emerging role of branched-chain amino acids in insulin resistance and metabolism","volume":"8","author":"Yoon","year":"2016","journal-title":"Nutrients"}],"updated-by":[{"DOI":"10.2337\/dc22-er03c","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000}}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/12\/2738\/642108\/dc202975.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/12\/2738\/642108\/dc202975.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T06:43:44Z","timestamp":1647153824000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/44\/12\/2738\/138494\/Characteristics-of-the-Gut-Microbiota-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,10,7]]},"published-print":{"date-parts":[[2021,12,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc20-2975","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.16441407","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.16441407.v1","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.16441407.v2","asserted-by":"object"}]},"ISSN":["0149-5992"],"issn-type":[{"value":"0149-5992","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10,7]]}}}