{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:15Z","timestamp":1787026515156,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170722"],"award-info":[{"award-number":["82170722"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of\n                      <jats:italic>Actinobacteriota<\/jats:italic>\n                      and\n                      <jats:italic>Verrucomicrobiota<\/jats:italic>\n                      was significantly higher, while\n                      <jats:italic>Bacteroidota<\/jats:italic>\n                      reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      ,\n                      <jats:italic>Akkermansia, and Streptococcus<\/jats:italic>\n                      were enriched, while only 4 genera including\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      ,\n                      <jats:italic>Tyzzerella<\/jats:italic>\n                      ,\n                      <jats:italic>Pseudomonas<\/jats:italic>\n                      , and\n                      <jats:italic>Anaerostignum<\/jats:italic>\n                      decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.973760","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T08:53:19Z","timestamp":1666169599000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jipeng","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhui","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Feng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiren","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023144","article-title":"Molecular mechanisms of amyloidosis","volume":"349","author":"Merlini","year":"2003","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1992.03490200198025","article-title":"Plasma cell dyscrasias","volume":"268","author":"Barlogie","year":"1992","journal-title":"Jama"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.08.041","article-title":"Incidence of Al amyloidosis in Olmsted county, Minnesota, 1990 through 2015","volume":"94","author":"Kyle","year":"2019","journal-title":"Mayo Clinic Proc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25819","article-title":"Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment","volume":"95","author":"Gertz","year":"2020","journal-title":"Am J Hematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.01285","article-title":"Bortezomib, melphalan, and dexamethasone for light-chain amyloidosis","volume":"38","author":"Kastritis","year":"2020","journal-title":"J Clin Oncol: Off J Am Soc Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1056\/NEJMoa2028631","article-title":"Daratumumab-based treatment for immunoglobulin light-chain amyloidosis","volume":"385","author":"Kastritis","year":"2021","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41408-021-00483-7","article-title":"Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021","volume":"11","author":"Hasib Sidiqi","year":"2021","journal-title":"Blood Cancer J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s40168-020-00854-5","article-title":"Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria","volume":"8","author":"Jian","year":"2020","journal-title":"Microbiome"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.919988","article-title":"Fecal microbiota taxonomic shifts in Chinese multiple myeloma patients analyzed by quantitative polimerase chain reaction (Qpcr) and 16s rrna high-throughput sequencing","volume":"25","author":"Zhang","year":"2019","journal-title":"Med Sci Monit"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4832","DOI":"10.1038\/s41467-018-07305-8","article-title":"Microbiota-driven interleukin-17-Producing cells and eosinophils synergize to accelerate multiple myeloma progression","volume":"9","author":"Calcinotto","year":"2018","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006923","article-title":"Fecal microbiota diversity disruption and clinical outcomes after auto-hct: A multicenter observational study","volume":"137","author":"Khan","year":"2021","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019032276","article-title":"Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition","volume":"3","author":"Pianko","year":"2019","journal-title":"Blood Adv"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215258","article-title":"Specific changes in faecal microbiota are associated with familial Mediterranean fever","volume":"78","author":"Deshayes","year":"2019","journal-title":"Ann Rheumatic Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230x-10-133","article-title":"Intestinal epithelial serum amyloid a modulates bacterial growth in vitro and pro-inflammatory responses in mouse experimental colitis","volume":"10","author":"Eckhardt","year":"2010","journal-title":"BMC Gastroenterol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e5842","DOI":"10.1371\/journal.pone.0005842","article-title":"Regulation of serum amyloid A3 (Saa3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota","volume":"4","author":"Reigstad","year":"2009","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2015-0369","article-title":"Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1","volume":"41","author":"Jang","year":"2016","journal-title":"Appl Physiol Nutrition Metab = Physiologie Appliquee Nutr Metabolisme"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2007.01418.x","article-title":"Amyloid adhesins are abundant in natural biofilms","volume":"9","author":"Larsen","year":"2007","journal-title":"Environ Microbiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3233\/jad-131394","article-title":"Can a bacterial endotoxin be a key factor in the kinetics of amyloid fibril formation","volume":"39","author":"Asti","year":"2014","journal-title":"J Alzheimer\u2019s Disease: JAD"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501814102","article-title":"Protein fibrils in nature can enhance amyloid protein a amyloidosis in mice: Cross-seeding as a disease mechanism","volume":"102","author":"Lundmark","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020712-163913","article-title":"Aa amyloidosis: Pathogenesis and targeted therapy","volume":"10","author":"Westermark","year":"2015","journal-title":"Annu Rev Pathol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/s0889-8553(05)70022-4","article-title":"Systemic amyloidosis and the gastrointestinal tract","volume":"27","author":"Friedman","year":"1998","journal-title":"Gastroenterol Clinics North America"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.01.010","article-title":"Prolonged elevation in hippocampal a\u03b2 and cognitive deficits following repeated endotoxin exposure in the mouse","volume":"229","author":"Kahn","year":"2012","journal-title":"Behav Brain Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/srep41802","article-title":"Reduction of abeta amyloid pathology in Appps1 transgenic mice in the absence of gut microbiota","volume":"7","author":"Harach","year":"2017","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.08.019","article-title":"Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly","volume":"49","author":"Cattaneo","year":"2017","journal-title":"Neurobiol Aging"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2016.00256","article-title":"Effect of probiotic supplementation on cognitive function and metabolic status in alzheimer\u2019s disease: A randomized, double-blind and controlled trial","volume":"8","author":"Akbari","year":"2016","journal-title":"Front Aging Neurosci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn326","article-title":"Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: Standards for study design","volume":"100","author":"Pepe","year":"2008","journal-title":"J Natl Cancer Institute"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20381","article-title":"Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (Al): A consensus opinion from the 10th international symposium on amyloid and amyloidosis, tours, France, 18-22 April 2004","volume":"79","author":"Gertz","year":"2005","journal-title":"Am J Hematol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.38.5724","article-title":"Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements","volume":"30","author":"Kumar","year":"2012","journal-title":"J Clin Oncol: Off J Am Soc Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.37.7614","article-title":"New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: Impact on survival outcomes","volume":"30","author":"Palladini","year":"2012","journal-title":"J Clin Oncol: Off J Am Soc Clin Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13506129.2020.1868810","article-title":"Clarification on the definition of complete haematologic response in light-chain (Al) amyloidosis","volume":"28","author":"Palladini","year":"2021","journal-title":"Amyloid: Int J Exp Clin Investigation: Off J Int Soc Amyloidosis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.557368","article-title":"A comparative study of the gut microbiota associated with immunoglobulin a nephropathy and membranous nephropathy","volume":"10","author":"Dong","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0548-6","article-title":"Picrust2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"13537","DOI":"10.1038\/s41598-017-13601-y","article-title":"Gut microbiome alterations in alzheimer\u2019s disease","volume":"7","author":"Vogt","year":"2017","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/aem.05548-11","article-title":"Novel probiotic bifidobacterium longum subsp. infantis cect 7210 strain active against rotavirus infections","volume":"77","author":"Mu\u00f1oz","year":"2011","journal-title":"Appl Environ Microbiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1177\/0148607111430817","article-title":"Bifidobacterium lactis Bb12 enhances intestinal antibody response in formula-fed infants: A randomized, double-blind, controlled trial","volume":"36","author":"Holscher","year":"2012","journal-title":"JPEN J Parenteral Enteral Nutr"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.2007.07046","article-title":"Antimicrobial and immunomodulatory effects of bifidobacterium strains: A review","volume":"30","author":"Lim","year":"2020","journal-title":"J Microbiol Biotechnol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2018.1517725","article-title":"A next generation probiotic, akkermansia muciniphila","volume":"59","author":"Zhai","year":"2019","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4953120","article-title":"Treatment with a monoclonal anti-Il-12p40 antibody induces substantial gut microbiota changes in an experimental colitis model","volume":"2016","author":"Castro-Mej\u00eda","year":"2016","journal-title":"Gastroenterol Res Pract"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e76520","DOI":"10.1371\/journal.pone.0076520","article-title":"Extracellular vesicles derived from gut microbiota, especially akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis","volume":"8","author":"Kang","year":"2013","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2018.03.016","article-title":"Exploring bacteroidetes: Metabolic key points and immunological tricks of our gut commensals","volume":"50","author":"Gibiino","year":"2018","journal-title":"Digestive Liver disease: Off J Ital Soc Gastroenterol Ital Assoc Stud Liver"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3796359","article-title":"Association study of gut flora in coronary heart disease through high-throughput sequencing","volume":"2017","author":"Cui","year":"2017","journal-title":"BioMed Res Int"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nature18309","article-title":"Acetate mediates a microbiome-Brain-\u03b2-Cell axis to promote metabolic syndrome","volume":"534","author":"Perry","year":"2016","journal-title":"Nature"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3920\/BM2016.0189","article-title":"Gut microbiota composition strongly correlates to peripheral insulin sensitivity in obese men but not in women","volume":"8","author":"Most","year":"2017","journal-title":"Benef Microbes"},{"key":"B45","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1007\/s11910-017-0802-6","article-title":"Microbiota-Brain-Gut axis and neurodegenerative diseases","volume":"17","author":"Quigley","year":"2017","journal-title":"Curr Neurol Neurosci Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/art.39785","article-title":"Suppression of inflammatory arthritis by human gut-derived prevotella histicola in humanized mice","volume":"68","author":"Marietta","year":"2016","journal-title":"Arthritis Rheumatol (Hoboken NJ)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.973760\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T08:53:26Z","timestamp":1666169606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.973760\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,19]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2022.973760"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.973760","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,19]]},"article-number":"973760"}}