{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:52:19Z","timestamp":1791381139264,"version":"4.3.3"},"reference-count":44,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Schizophrenia (SCZ) has a complex etiology, and growing evidence implicates the microbiota-gut-brain axis. Because abundance-based profiling does not identify taxa closely engaged by mucosal immunity, we used immunoglobulin A (IgA)-based bacterial sorting to prioritize candidate SCZ-associated gut bacteria and evaluated cultured consortia in mouse models. Fecal samples were collected from participants with SCZ, other mental disorders, and healthy controls, which underwent 16S rRNA gene sequencing before and after magnetic separation of IgA-coated (IgA+) and non-IgA-coated (IgA\u2212) bacteria. Taxa prioritized by the IgA coating index were anaerobically cultured, pooled into defined IgA+ and IgA\u2212 consortia, and administered to germ-free (GF) C57BL\/6J, antibiotic-pretreated\n Rag1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n SPF, and conventional SPF C57BL\/6J mice. In the bacterial treatment groups, MK-801 was introduced only during the final 7 days of consortium gavage; the GF NaCl control received intraperitoneal saline during the corresponding final 7-day period. Behavioral, serological, colonic, and hippocampal outcomes were assessed according to the endpoints specified for each experiment. Candidate IgA+ taxa included\n Streptococcus<\/jats:italic>\n ,\n Pseudomonas<\/jats:italic>\n , and\n Parabacteroides<\/jats:italic>\n , whereas IgA\u2212 candidates included\n Collinsella<\/jats:italic>\n ,\n Eggerthella<\/jats:italic>\n ,\n Bifidobacterium<\/jats:italic>\n ,\n Bacteroides<\/jats:italic>\n ,\n Enterococcus<\/jats:italic>\n , and\n Clostridium<\/jats:italic>\n . In experiment 1, the GF IgA+ and GF IgA\u2212 groups differed in open-field center-zone time (\n P<\/jats:italic>\n = 0.032). Marble-burying behavior showed a significant overall difference among the five groups (\n P<\/jats:italic>\n = 0.040), with a significant pairwise difference between GF IgA+ and GF IgA\u2212 mice (\n P<\/jats:italic>\n = 0.022). Y-maze spontaneous alternation showed no overall group difference (\n P<\/jats:italic>\n = 0.81). Forced-swim immobility showed a significant overall group effect (\n P<\/jats:italic>\n = 0.020), with significant pairwise differences between GF IgA+ and GF IgA\u2212 mice (\n P<\/jats:italic>\n = 0.020) and between GF IgA\u2212 and\n Rag1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n IgA\u2212 mice (\n P<\/jats:italic>\n = 0.030). IL-6 was frequently undetectable and was not compared statistically; TNF-\u03b1 showed a significant overall analysis of variance group effect (\n P<\/jats:italic>\n = 0.040), but no Tukey-adjusted pairwise comparison was significant. Colon length also showed a significant overall group effect (\n P<\/jats:italic>\n = 0.010), with shorter colons in the GF IgA+ group than in the GF saline and GF IgA\u2212 groups (both pairwise\n P<\/jats:italic>\n = 0.016), although colonic histology was largely normal. Descriptive hippocampal alterations were observed in GF IgA+ consortium mice. In conventional specific pathogen-free mice, MK-801 was introduced after the first 7 days of consortium gavage and continued during the final 7 days; under this exposure schedule, the IgA+ consortium was associated with greater colonic mucosal injury than the IgA\u2212 consortium. IgA-based prioritization identified candidate SCZ-associated taxa, and the resulting consortia were associated with distinct, context-dependent host responses. Individual-taxon causality remains unproven and requires validation in larger cohorts and rigorously matched animal studies.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n Schizophrenia (SCZ) is a severe psychiatric disorder with incompletely understood biological mechanisms. Although gut microbial alterations have been reported in SCZ, abundance alone does not show which bacteria are most closely recognized by the intestinal immune system. Here, IgA-based sorting was used to prioritize immune-targeted bacterial taxa, and cultured IgA+ and IgA\u2212 consortia were evaluated in mouse experiments. The two consortia were associated with different behavioral and tissue outcomes under specific experimental conditions. In both animal experiments, bacterial gavage preceded MK-801, which was introduced during the final 7 days of gavage as a late pharmacological challenge. These findings provide a hypothesis-generating framework for studying mucosal immune-microbiota interactions in SCZ, but they do not support diagnostic, therapeutic, or strain-specific causal claims.<\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/msystems.00786-26","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:01:00Z","timestamp":1791378060000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Application of IgA-Seq in schizophrenia to identify key gut bacteria that promote abnormal behavior in mice"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5512-0207","authenticated-orcid":true,"given":"Caihong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]},{"id":[{"id":"https:\/\/ror.org\/00t33hh48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Engineering, School of Medicine, The Chinese University of Hong Kong (Shenzhen)","place":["Shenzhen, China"]},{"name":"Guangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering, The Chinese University of Hong Kong (Shenzhen)","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Longgang District Central Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinmei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Department of Psychiatry, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People\u2019s Hospital of Shenzhen","place":["Shenzhen, 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China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging, Key Laboratory of Bacterial Resistance and Prevention, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-4530","authenticated-orcid":false,"given":"Chen-zhong","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t33hh48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Engineering, School of Medicine, The Chinese University of Hong Kong (Shenzhen)","place":["Shenzhen, China"]},{"name":"Guangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering, The Chinese University of Hong Kong (Shenzhen)","place":["Shenzhen, 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