{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:34:34Z","timestamp":1789173274155,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While immunoblobulin A(IgA) dominates gut mucosal immunity, the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) in host-microbiota interactions remain poorly characterized, particularly in schizophrenia (SCZ). Although gut dysbiosis and immune activation have been implicated in SCZ,the contribution of IgG\/IgM-coated gut microbiota to disease associated inflammation and behavioral alterations remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We recruited six patients with SCZ, six with other psychiatric disorders (OPD) and six age- and sex- matched healthy controls. IgG\/IgM-coated gut microbiota were isolated from 100 mg fecal samples via magnetic-activated cell sorting (MACS) and profiled by 16S rRNA sequencing. A pilot an IgG\/IgM-coated fecal microbiota transplantation (FMT) using anaerobically cultured human intestinal microbiota was conducted in mice to assess the effects on gut pathology, peripheral immunity, and behavior. The percentage of neutrophil granulocyte in peripheral blood was quantified microscopically, and statistical analyses were performed using one-way ANOVA in GraphPad Prism 8, with (p &amp;lt; 0.05.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proportions of IgM-coated bacteria was significantly higher in patients with SCZ than in healthy controls (p&amp;lt;0.05), with enrichment of Rhodococcuss, Shigella, Clostridium and Streptococcus. Mice receiving a mixture of high-IgM-coated intestinal bacteria mixture showed reduced depletion of peripheral neutrophils, mild colon shortening, and mucosal inflammation compared with those receiving low IgM-coated or uncoated bacteria. In contrast, high IgG-coated bacteria, enriched in\n                      <jats:italic>Rhodococcuss<\/jats:italic>\n                      ,\n                      <jats:italic>Acinetobater<\/jats:italic>\n                      and\n                      <jats:italic>Pseudomonas<\/jats:italic>\n                      , decreased in SCZ, but induced similar inflammatory gut changes. No IgG- nor IgM- induced anxiety-like behavior were detect in the mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal that IgG\/IgM-coated intestinal microbiota display distinct immunoreactive microbiota signatures associated with SCZ. These coated communities promote gut inflammation without inducing anxiety-like behavior, highlighting their potential as novel biomarkers of SCZ-associated immune dysregulation and as targets for personalized therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2025.1689069","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:34:30Z","timestamp":1768286070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["IgG\/IgM-coated gut microbiota in schizophrenia: associations with inflammation disease activity"],"prefix":"10.3389","volume":"16","author":[{"given":"Guohao","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2025.1629032","article-title":"Results of the Global Burden of Disease study for schizophrenia: trends from 1990 to 2021 and projections to 2050","volume":"16","author":"Zhan","year":"2025","journal-title":"Front Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12993-021-00180-2","article-title":"Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis","volume":"17","author":"Patrono","year":"2021","journal-title":"Behav Brain functions: BBF"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/s42003-025-08456-3","article-title":"Analysis of biased allelic enhancer activity of schizophrenia-linked common variants","volume":"8","author":"Gao","year":"2025","journal-title":"Commun Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2025.01.008","article-title":"Recent advances in schizophrenia genomics and emerging clinical implications","volume":"48","author":"Bigdeli","year":"2025","journal-title":"Psychiatr Clinics North America"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106799","article-title":"The brain-gut-microbiota interplay in depression: A key to design innovative therapeutic approaches","volume":"192","author":"Varesi","year":"2023","journal-title":"Pharmacol Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.812293","article-title":"Multi-omics analysis reveals aberrant gut-metabolome-immune network in schizophrenia","volume":"13","author":"Fan","year":"2022","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2024.05.001","article-title":"Pilot study indicates that a gluten-free diet lowers oxidative stress for gluten-sensitive persons with schizophrenia","volume":"269","author":"Kim","year":"2024","journal-title":"Schizophr Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2024.01.036","article-title":"Associations of gut microbiota alterations with clinical, metabolic, and immune-inflammatory characteristics of chronic schizophrenia","volume":"171","author":"Misiak","year":"2024","journal-title":"J Psychiatr Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1186\/s12967-024-05533-9","article-title":"Altered gut microbiota and systemic immunity in Chinese patients with schizophrenia comorbid with metabolic syndrome","volume":"22","author":"Ling","year":"2024","journal-title":"J Trans Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2022.100483","article-title":"Composite immune marker scores associated with severe mental disorders and illness course","volume":"24","author":"Elkjaer Greenwood Ormerod","year":"2022","journal-title":"Brain behavior Immun - Health"},{"key":"B11","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1186\/s12888-024-06032-3","article-title":"Elevated serum IL-17 A and CCL20 levels as potential biomarkers in major psychotic disorders: a case-control study","volume":"24","author":"Ghasemi Noghabi","year":"2024","journal-title":"BMC Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157264","article-title":"Pathogenic mechanisms of cerebral ischemia and potential gut-brain axis-oriented therapeutic strategies","volume":"148","author":"Zhuang","year":"2025","journal-title":"Phytomedicine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ptr.70067","article-title":"Zingibroside R1 Isolated From Achyranthes bidentata Blume Ameliorates LPS\/D-GalN-Induced Liver Injury by Regulating Succinic Acid Metabolism via the Gut Microbiota","author":"Guo","year":"2025","journal-title":"Phytotherapy Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41385-019-0227-4","article-title":"IgA and the intestinal microbiota: the importance of being specific","volume":"13","author":"Pabst","year":"2020","journal-title":"Mucosal Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"9254","DOI":"10.3390\/ijms21239254","article-title":"Secretory IgA in intestinal mucosal secretions as an adaptive barrier against microbial cells","volume":"21","author":"Pietrzak","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.0105-2896.2005.00283.x","article-title":"Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties","volume":"206","author":"Brandtzaeg","year":"2005","journal-title":"Immunol Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1159\/000521259","article-title":"The possible pathogenic role of IgG4-producing plasmablasts in stricturing crohn\u2019s disease","volume":"89","author":"Bushara","year":"2022","journal-title":"Pathobiology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.62641\/aep.v52i3.1648","article-title":"Identification of immune-related gene signature in schizophrenia","volume":"52","author":"Wu","year":"2024","journal-title":"Actas Esp Psiquiatr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf9655","article-title":"IgA-coated E. coli enriched in Crohn\u2019s disease spondyloarthritis promote T(H)17-dependent inflammation","volume":"9","author":"Viladomiu","year":"2017","journal-title":"Sci Transl Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12425","article-title":"Emerging roles for antigen presentation in establishing host-microbiome symbiosis","volume":"272","author":"Bessman","year":"2016","journal-title":"Immunol Rev"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-024-02121-y","article-title":"Mouse IgA modulates human gut microbiota with inflammatory bowel disease patients","volume":"59","author":"Takahashi","year":"2024","journal-title":"J\u00a0Gastroenterol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.006","article-title":"Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease","volume":"158","author":"Palm","year":"2014","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.960208","article-title":"Human umbilical cord mesenchymal stem cells regulate immunoglobulin a secretion and remodel the diversification of intestinal microbiota to improve colitis","volume":"12","author":"Liu","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-022-01429-2","article-title":"Dynamics of the gut microbiome, IgA response, and plasma metabolome in the development of pediatric celiac disease","volume":"11","author":"Girdhar","year":"2023","journal-title":"Microbiome"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo03579g","article-title":"Long-term exclusive enteral nutrition remodels the gut microbiota and alleviates TNBS-induced colitis in mice","volume":"13","author":"Li","year":"2022","journal-title":"Food Funct"},{"key":"B26","doi-asserted-by":"publisher","first-page":"eade2335","DOI":"10.1126\/sciimmunol.ade2335","article-title":"IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation","volume":"8","author":"Conrey","year":"2023","journal-title":"Sci Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.immuni.2017.06.013","article-title":"Human secretory IgM emerges from plasma cells clonally related to gut memory B cells and targets highly diverse commensals","volume":"47","author":"Magri","year":"2017","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-025-02013-8","article-title":"Secretory IgM regulates gut microbiota homeostasis and metabolism","volume":"10","author":"Ding","year":"2025","journal-title":"Nat Microbiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"eado5294","DOI":"10.1126\/science.ado5294","article-title":"Breast milk IgG engages the mouse neonatal immune system to instruct responses to gut antigens","volume":"389","author":"Shenoy","year":"2025","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"16672","DOI":"10.1038\/s41598-021-96289-5","article-title":"Immunoglobulin subtype-coated bacteria are correlated with the disease activity of inflammatory bowel disease","volume":"11","author":"Masu","year":"2021","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/imm.13518","article-title":"Luminal bacteria coated with IgA and IgG during intestinal inflammation as a new and abundant stimulus for colonic macrophages","volume":"167","author":"Maccio-Maretto","year":"2022","journal-title":"Immunology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1102938108","article-title":"Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice","volume":"108","author":"Goodman","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.002","article-title":"Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis","volume":"118","author":"Rakoff-Nahoum","year":"2004","journal-title":"Cell"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.842911","article-title":"Patients with inflammatory bowel disease show IgG immune responses towards specific intestinal bacterial genera","volume":"13","author":"Bourgonje","year":"2022","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.3390\/ph17081020","article-title":"Is there an interplay between environmental factors, microbiota imbalance, and cancer chemotherapy-associated intestinal mucositis","volume":"17","author":"Fernandes","year":"2024","journal-title":"Pharm (Basel)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2025.102854","article-title":"Serological insights into MERS-CoV dynamics of antibody responses during acute and convalescent phases and their clinical relevance for diagnostics and immunity","volume":"18","author":"Shrwani","year":"2025","journal-title":"J Infect Public Health"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000203","article-title":"IgM, Fc mu Rs, and malarial immune evasion","volume":"184","author":"Czajkowsky","year":"2010","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.chom.2020.09.012","article-title":"Distinct polysaccharide utilization determines interspecies competition between intestinal prevotella spp","volume":"28","author":"G\u00e1lvez","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12328-017-0813-5","article-title":"Gut microbiota in the pathogenesis of inflammatory bowel disease","volume":"11","author":"Nishida","year":"2018","journal-title":"Clin J Gastroenterol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13391","article-title":"Neutrophil-T cell crosstalk in inflammatory bowel disease","volume":"164","author":"Kvedaraite","year":"2021","journal-title":"Immunology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.immuni.2024.11.008","article-title":"Elevated IL-22 as a result of stress-induced gut leakage suppresses septal neuron activation to ameliorate anxiety-like behavior","volume":"58","author":"Xia","year":"2025","journal-title":"Immunity"},{"key":"B42","doi-asserted-by":"publisher","first-page":"6422","DOI":"10.1038\/s41467-025-61544-0","article-title":"Gut microbiota and brain-resident CD4(+) T cells shape behavioral outcomes in autism spectrum disorder","volume":"16","author":"Park","year":"2025","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.62641\/aep.v52i4.1672","article-title":"Correlations between immunoinflammatory factor levels and cognitive functions and brain structural magnetic resonance imaging features among patients with primary schizophrenia","volume":"52","author":"Pan","year":"2024","journal-title":"Actas Esp Psiquiatr"},{"key":"B44","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13099-018-0276-3","article-title":"Microbiota profile in new-onset pediatric Crohn\u2019s disease: data from a non-Western population","volume":"10","author":"El Mouzan","year":"2018","journal-title":"Gut Pathog"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3233\/jad-240597","article-title":"Characterizing gut microbiota in older chinese adults with cognitive impairment: A cross-sectional study","volume":"101","author":"Wang","year":"2024","journal-title":"J Alzheimers Dis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105722","article-title":"Cognition and gut microbiota in schizophrenia spectrum and mood disorders: A systematic review","volume":"162","author":"Frileux","year":"2024","journal-title":"Neurosci Biobehav Rev"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2024.03.088","article-title":"Fecal microbiota transplant on Escherichia-Shigella gut composition and its potential role in the treatment of generalized anxiety disorder: A systematic review","volume":"354","author":"Baske","year":"2024","journal-title":"J Affect Disord"},{"key":"B48","doi-asserted-by":"publisher","first-page":"sbaf110","DOI":"10.1093\/schbul\/sbaf110","article-title":"Distinct gut microbial signatures and diminished anti-inflammatory effect of short-chain fatty acids in schizophrenia with immune activation","volume":"21","author":"He","year":"2025","journal-title":"Schizophr Bull"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2023-330677","article-title":"Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn\u2019s disease","volume":"73","author":"Eriksen","year":"2024","journal-title":"Gut"},{"key":"B50","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41590-020-00828-7","article-title":"Proinflammatory IgG Fc structures in patients with severe COVID-19","volume":"22","author":"Chakraborty","year":"2021","journal-title":"Nat\u00a0Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c200020","article-title":"Innate immune cells and hypertension: neutrophils and neutrophil extracellular traps (NETs)","volume":"11","author":"McCarthy","year":"2021","journal-title":"Compr Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-025-01522-0","article-title":"The dual roles of peptidoglycans: NOD1 and NOD2 inversely regulate bone metabolism","volume":"57","author":"Park","year":"2025","journal-title":"Exp Mol Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.5c01864","article-title":"Surfactant-mediated droplet spreading analysis on liquid crystal-infused porous surfaces: A label-free biosensor for sensitive lipopolysaccharide detection","volume":"10","author":"Zhao","year":"2025","journal-title":"ACS sensors"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700261","article-title":"Bacterial siderophores hijack neutrophil functions","volume":"198","author":"Saha","year":"2017","journal-title":"J Immunol"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2025.1689069\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:34:32Z","timestamp":1768286072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2025.1689069\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":54,"alternative-id":["10.3389\/fpsyt.2025.1689069"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2025.1689069","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"article-number":"1689069"}}