{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T19:36:11Z","timestamp":1783798571266,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: In many neurodegenerative diseases, the pathological changes occurring in the central nervous system may be reflected in the periphery. The aim of this study was to examine the possible relationship between the retina, choroid, and nerve fibre layer thicknesses measured on optic coherence tomography (OCT) and the serum microbiota metabolite levels of trimethyl amine-N-oxide (TMAO), S-equol, Indoxyl sulphate (IS), and Maresin 1 (MaR1). Materials and Methods: This study included a total of 60 subjects, comprising 30 patients diagnosed with schizophrenia and a control group of 30 healthy individuals. A sociodemographic form was given to all the subjects and the Positive and Negative Syndrome Scale (PANSS) to the schizophrenia patients. The eye fundus was evaluated with OCT. A 5 mL blood sample was taken from the arm of each subject, and the microbiota metabolite levels of TMAO, S-equol, IS, and MaR1 were examined. Results: The retina nerve fibre layer (RNFL) analysis results showed that the RNFL superior (p = 0.016), inferior (p = 0.002), central choroid (p = 0.033), nasal choroid (p = 0.004), temporal choroid (p = 0.038), and TMAO (p = 0.001) values were significantly lower in the schizophrenia patients than in the control group. In the patient group, a significant negative correlation was determined between the RNFL temporal measurements and IS, as well as a significant positive correlation between the central choroid measurement and the nasal choroid and temporal choroid measurements and between the nasal choroid and temporal choroid measurements. A statistically significant positive correlation was seen between S-equol and TMAO. A significant negative correlation was seen between the MaR1 level and age and disease duration. Conclusions: The study results showed that fundus changes are associated with serum microbiota metabolite levels in schizophrenia patients. Therefore, these parameters may be considered potential exploratory biomarkers; however, their clinical applicability requires validation in larger longitudinal studies.<\/jats:p>","DOI":"10.3390\/medicina62030528","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:12:24Z","timestamp":1773321144000},"page":"528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Can the Posterior Segment Findings of the Eye and Serum Microbiota Metabolites Be a Biomarker in Schizophrenia?"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-6691","authenticated-orcid":false,"given":"Sinem","family":"Keser","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Elaz\u0131\u011f Fethi Sekin City Hospital, 23280 Elaz\u0131\u011f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9951-9093","authenticated-orcid":false,"given":"Sevler","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Elaz\u0131\u011f Fethi Sekin City Hospital, 23280 Elaz\u0131\u011f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-3250","authenticated-orcid":false,"given":"S\u00fcleyman","family":"Ayd\u0131n","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, F\u0131rat University, 23119 Elaz\u0131\u011f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fclide","family":"Kele\u015f","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Elaz\u0131\u011f Fethi Sekin City Hospital, 23280 Elaz\u0131\u011f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Aksoy","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Faculty of Engineering and Natural Sciences, Malatya Turgut \u00d6zal University, 44000 Malatya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Emre","sequence":"additional","affiliation":[{"name":"Department of Anatomy, F\u0131rat University, 23119 Elaz\u0131\u011f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Publishing.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.schres.2022.03.004","article-title":"Neurodegenerative model of schizophrenia: Growing evidence to support a revisit","volume":"243","author":"Stone","year":"2022","journal-title":"Schizophr. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/S0140-6736(96)07495-8","article-title":"Global mortality, disability, and the contribution of risk factors: Global burden of disease study","volume":"349","author":"Murray","year":"1997","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2147\/NDT.S225643","article-title":"Negative symptoms in schizophrenia: A review and clinical guide for recognition, assessment, and treatment","volume":"16","author":"Correll","year":"2020","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bpsgos.2023.08.013","article-title":"Optical coherence tomography in schizophrenia spectrum disorders: A systematic review and meta-analysis","volume":"4","author":"Shew","year":"2023","journal-title":"Biol. Psychiatry Glob. Open Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.schres.2017.07.018","article-title":"Multiple retinal anomalies in schizophrenia","volume":"195","author":"Adams","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrneurol.2012.227","article-title":"The retina as a window to the brain\u2014From eye research to CNS disorders","volume":"9","author":"London","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/schbul\/sbac085","article-title":"Mapping retinal abnormalities in psychosis: Meta-analytical evidence for focal peripapillary and macular reductions","volume":"48","author":"Radua","year":"2022","journal-title":"Schizophr. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/schbul\/sbz029","article-title":"A meta-analysis of retinal cytoarchitectural abnormalities in schizophrenia and bipolar disorder","volume":"46","author":"Lizano","year":"2020","journal-title":"Schizophr. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41380-023-02340-4","article-title":"Retina as a potential biomarker in schizophrenia spectrum disorders: A systematic review and meta-analysis of optical coherence tomography and electroretinography","volume":"29","author":"Komatsu","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00406-022-01455-z","article-title":"Optical coherence tomography reveals retinal thinning in schizophrenia spectrum disorders","volume":"273","author":"Boudriot","year":"2023","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/jamapsychiatry.2023.0171","article-title":"Association between retinal features from multimodal imaging and schizophrenia","volume":"80","author":"Wagner","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1017\/S0033291717003555","article-title":"Optical coherence tomography indices of structural retinal pathology in schizophrenia","volume":"48","author":"Silverstein","year":"2018","journal-title":"Psychol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114985","DOI":"10.1016\/j.biopha.2023.114985","article-title":"Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review","volume":"164","author":"Chu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s10482-020-01474-7","article-title":"Human gut microbiota\/microbiome in health and diseases: A review","volume":"113","author":"Gomaa","year":"2020","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mousa, W.K., Chehadeh, F., and Husband, S. (2022). Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.906258"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kandpal, M., Indari, O., Baral, B., Jakhmola, S., Tiwari, D., Bhandari, V., Pandey, R.K., Bala, K., Sonawane, A., and Jha, H.C. (2022). Dysbiosis of gut microbiota from the perspective of the gut\u2013brain axis: Role in the provocation of neurological disorders. Metabolites, 12.","DOI":"10.3390\/metabo12111064"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105840","DOI":"10.1016\/j.phrs.2021.105840","article-title":"The role of microbiota\u2013gut\u2013brain axis in neuropsychiatric and neurological disorders","volume":"172","author":"Doboszewska","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41564-018-0307-3","article-title":"GABA-modulating bacteria of the human gut microbiota","volume":"4","author":"Strandwitz","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Munawar, N., Ahsan, K., Muhammad, K., Ahmad, A., Anwar, M.A., Shah, I., Al Ameri, A.K., and Al Mughairbi, F. (2021). Hidden role of gut microbiome dysbiosis in schizophrenia: Antipsychotics or psychobiotics as therapeutics?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147671"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shi, L., Ju, P., Meng, X., Wang, Z., Yao, L., Zheng, M., Cheng, X., Li, J., Yu, T., and Xia, Q. (2023). Intricate role of intestinal microbe and metabolite in schizophrenia. BMC Psychiatry, 23.","DOI":"10.1186\/s12888-023-05329-z"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.14336\/AD.2022.0104","article-title":"Functions of gut microbiota metabolites: Current status and future perspectives","volume":"13","author":"Liu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhen, J., Zhou, Z., He, M., Han, H.X., Lv, E.H., Wen, P.B., Liu, X., Wang, Y.T., Cai, X.C., and Tian, J.Q. (2023). The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1085041"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13781","DOI":"10.1038\/s41598-017-13739-9","article-title":"TMAO is associated with mortality: Impact of modestly impaired renal function","volume":"7","author":"Gruppen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"936","DOI":"10.17305\/bb.2023.8893","article-title":"The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review","volume":"23","author":"Oktaviono","year":"2023","journal-title":"Biomol. Biomed."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sekikawa, A., Wharton, W., Butts, B., Veliky, C.V., Garfein, J., Li, J., Goon, S., Fort, A., Li, M., and Hughes, T.M. (2022). Potential protective mechanisms of S-equol, a metabolite of soy isoflavone by the gut microbiome, on cognitive decline and dementia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911921"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1002\/jat.4366","article-title":"Effects of the uremic toxin indoxyl sulphate on human microvascular endothelial cells","volume":"42","author":"Colombo","year":"2022","journal-title":"J. Appl. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1093\/ajh\/hpaa053","article-title":"Role of S-equol, indoxyl sulfate, and trimethylamine N-oxide on vascular function","volume":"33","author":"Matsumoto","year":"2020","journal-title":"Am. J. Hypertens."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bulu, A., Onalan, E., Yakar, B., Bulu, G., Y\u0131ld\u0131r\u0131m, S.O., G\u00fcrsu, M.F., Kaplankaya, U., D\u00f6nder, E., and Kaymaz, T. (2025). Maresin 1 and CHI3L1 levels exhibit opposing trends and correlations with renal dysfunction in diabetic nephropathy. Medicina, 61.","DOI":"10.3390\/medicina61071247"},{"key":"ref_30","first-page":"eaaf7483","article-title":"Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses","volume":"8","author":"Leuti","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hanson, D.R., and Gottesman, I.I. (2005). Theories of schizophrenia: A genetic\u2013inflammatory\u2013vascular synthesis. BMC Med. Genet., 6.","DOI":"10.1186\/1471-2350-6-7"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Qi, D., Liu, P., Wang, Y., Tai, X., and Ma, S. (2024). Unveiling the gut microbiota blueprint of schizophrenia: A multilevel omics approach. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1452604"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/schbul\/13.2.261","article-title":"The positive and negative syndrome scale (PANSS) for schizophrenia","volume":"13","author":"Kay","year":"1987","journal-title":"Schizophr. Bull."},{"key":"ref_34","first-page":"23","article-title":"Validity and reliability of the Turkish version of the Positive and Negative Syndrome Scale (PANSS)","volume":"14","author":"Batur","year":"1999","journal-title":"Turk. Psikol. Derg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.psychres.2018.10.075","article-title":"Retinal nerve fiber layer thickness changes in schizophrenia: A meta-analysis of case-control studies","volume":"270","author":"Pan","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1007\/s11682-020-00281-y","article-title":"Aberrant inverted U-shaped brain pattern and trait-related retinal impairment in schizophrenia patients with combined auditory and visual hallucinations","volume":"15","author":"Zhuo","year":"2021","journal-title":"Brain Imaging Behav."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pscychresns.2011.08.011","article-title":"A window into the brain: An in vivo study of the retina in schizophrenia using optical coherence tomography","volume":"203","author":"Chu","year":"2012","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.2147\/NDT.S225982","article-title":"Alterations of glycerophospholipid and fatty acyl metabolism in multiple brain regions of schizophrenia microbiota recipient mice","volume":"15","author":"Liang","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/ajmg.b.32662","article-title":"Association between retinal features from multimodal imaging and schizophrenia","volume":"177","author":"Li","year":"2018","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kalagi, N.A., Thota, R.N., Stojanovski, E., Alburikan, K.A., and Garg, M.L. (2022). Association between plasma trimethylamine N-oxide levels and type 2 diabetes: A case-control study. Nutrients, 14.","DOI":"10.3390\/nu14102093"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1016\/j.jacc.2016.03.546","article-title":"Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with atherosclerotic burden","volume":"67","author":"Senthong","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shanmugham, M., Bellanger, S., and Leo, C.H. (2023). Gut-derived metabolite, trimethylamine-N-oxide (TMAO) in cardio-metabolic diseases: Detection, mechanism, and potential therapeutics. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040504"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1001\/jamapsychiatry.2021.0015","article-title":"Association between cardiovascular risk factors and cognitive impairment in people with schizophrenia: A systematic review and meta-analysis","volume":"78","author":"Hagi","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S0017","DOI":"10.5702\/massspectrometry.S0017","article-title":"Correlation between serum levels of protein-bound uremic toxins in hemodialysis patients measured by LC\/MS\/MS","volume":"2","author":"Itoh","year":"2013","journal-title":"Mass Spectrom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.21608\/ejhm.2023.306891","article-title":"Role of Maresin-1 in inflammatory resolution of psoriasis (Maresin-1, novel therapeutic alternative in psoriasis patients)","volume":"92","author":"Shaalan","year":"2023","journal-title":"Egypt. J. Hosp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40942-025-00646-9","article-title":"Effects of cigarette smoking on retinal thickness and choroidal vascularity index: A systematic review and meta-analysis","volume":"11","year":"2025","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.engmed.2024.100036","article-title":"Smoking associated metabolites from gut microbiota on health: Nicotine degradation brings hopes","volume":"1","author":"Zeng","year":"2024","journal-title":"EngMedicine"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/3\/528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:44:36Z","timestamp":1773326676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/3\/528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["medicina62030528"],"URL":"https:\/\/doi.org\/10.3390\/medicina62030528","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}