ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1652633
This article is part of the Research TopicThe Gut-Brain Axis: Microbiota-Driven Immune Modulation and its Impact on Neurological HealthView all 4 articles
Gut Mycobiota Dysbiosis and Systemic Immune Dysfunction in Chinese Schizophrenia Patients with Metabolic Syndrome
Provisionally accepted
Zongxin Ling1*
Yiwen Cheng1Zhiyong Lan2
Xia Liu1Zhangcheng Zhu3Wenwen Ding4Xiaocui Xu4Pian Yu2Xiaoxun Xu2
Li Shao5Qinghai Song6Rongxian Liao2- 1Zhejiang University, Hangzhou, China
- 2Third Hospital of Quzhou, Quzhou, China
- 3Wenzhou Medical University, Wenzhou, China
- 4Nantong University, Nantong, China
- 5Hangzhou Normal University, Hangzhou, China
- 6The Second People's Hospital of Lishui, Lishui, China
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While bacterial dysbiosis has been extensively studied in schizophrenia with metabolic syndrome (SZ-MetS), the role of gut mycobiota in this comorbidity remains unclear. This study represents the first comprehensive investigation of fungal communities in SZ-MetS patients (n=109) versus healthy controls (HCs, n=101) using ITS1 sequencing and multi-parameter immune profiling. Although global mycobiota structure showed no significant differences, compositional analyses revealed profound taxonomic shifts: pathobionts (Trichosporon asahii, Candida albicans, Lodderomyces elongisporus) were enriched, while putative beneficial species (Saccharomyces cerevisiae, Pleurotus ostreatus) were reduced in patients. Enterotyping identified two mycobiota clusters (Candida-dominant vs Aspergillus-dominant), though their distribution was similar between groups. Notably, machine learning revealed a six-species fungal signature with strong diagnostic potential (AUC = 0.86). Species-specific immune correlations were also observed: inflammatory cytokines such as IL-6 and MIP-1α were positively associated with Ustilago esculenta and Trichosporon asahii, but negatively correlated with Saccharomyces cerevisiae. Furthermore, fungal abundances were differentially correlated with metabolic and psychiatric parameters, with Lodderomyces linked to elevated triglycerides and S. cerevisiae associated with reduced symptom severity. These findings reveal that while overall fungal community structure is preserved, SZ-MetS exhibits distinct mycobiota alterations that interact with host immunity and clinical manifestations, suggesting fungi may contribute to the SZ-MetS vicious cycle through taxon-specific mechanisms.
Keywords: Schizophrenia, metabolic syndrome, Mycobiota, gut-brain axis, Immunological dysfunction
Received: 27 Jun 2025; Accepted: 19 Aug 2025.
Copyright: © 2025 Ling, Cheng, Lan, Liu, Zhu, Ding, Xu, Yu, Xu, Shao, Song and Liao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zongxin Ling, Zhejiang University, Hangzhou, China
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