2026-09-30 2026, Volume 1 Issue 3

  • Select all
  • ORIGINAL ARTICLE
    Hongyan Qi, Ting Yu, Weichen Liu, Ya Jiang, Die Chen, Li Gao, Hui Li, Yurong Tang

    Background: Chronic constipation (CC) frequently co-occurs with psychiatric distress (PD), complicating management. The gut microbiota is implicated in CC and the gut–brain axis, but whether fecal signatures can identify CC and stratify patients by psychiatric status remains unclear. This study aimed to develop and internally/externally validate two separate microbiota-based models: one discriminating patients with CC from healthy controls (HCs) and another identifying CC patients with PD (CPD) versus those without (CNPD).

    Methods: We curated gut microbiota profiles (16S rRNA) from public datasets (discovery cohort, n = 478) and our institutional cohort (external validation, n = 45). After quality control, taxonomic profiles and functional metagenomes (PICRUSt2) were generated. Differentially abundant genera and pathways were identified, with functional enrichment analysis (taxon set enrichment analysis). A two-step machine learning approach was employed: (1) a support vector machine (SVM) classifier distinguishing CC from HCs and (2) an Elastic Net classifier differentiating CPD from CNPD within patients with CC. Model performance was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), decision curve analysis, and clinical impact curves.

    Results: Alterations in gut microbial composition were observed across the groups. Compared with HCs, patients with CC exhibited reduced alpha diversity and distinct beta-diversity clustering, characterized by depletion of short-chain fatty acid (SCFA)-producing genera (e.g., Faecalibacterium and Roseburia) and enrichment of potentially pathogenic genera (e.g., Methanomassiliicoccus). Importantly, within patients with CC, the CPD subgroup showed further deviation from CNPD, including a specific reduction in Lachnospiraceae_ND3007_group and an increased abundance of Methanosphaera. The SVM model achieved a modest AUC of 0.71 for discriminating CC from HC, indicating limited discriminative capacity. The Elastic Net model demonstrated a lower but important discriminatory ability (AUC = 0.67) for identifying PD within patients with CC.

    Conclusion: This study provides proof of concept that gut microbiota-based models can distinguish patients with CC from healthy individuals with modest accuracy. Identifying PD within patients with CC has proven more challenging, and current models do not meet the performance standards required for clinical decision-making (e.g., AUC ≥ 0.80 for screening tools). Nevertheless, the microbial signatures, particularly taxa linked to neurotransmitter regulation and inflammation, support gut–brain axis involvement. These findings may serve as a risk indicator, but future improvements integrating clinical and metabolomic data are needed before any clinical application can be considered.

  • BRIEF REPORT
    Qianqian Li, Xiao Ding, Sheng Zhang, Faming Zhang
    2026, 1(3): 107-115. https://doi.org/10.1002/mmr3.70013

    Background: Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy. Survivors often enter a chronic phase characterized by drug-resistant epilepsy, cognitive impairment, behavioral and psychiatric symptoms, and long-term functional disability. Effective strategies for chronic-phase FIRES remain limited.

    Methods: We report a 17-year-old adolescent female patient with chronic-phase FIRES who received two courses of washed microbiota transplantation (WMT) via colonic transendoscopic enteral tube. Clinical outcomes were followed for 36 months, whereas metagenomic sequencing, urinary metabolomics, and 16S rRNA sequencing analyses focused on early post-WMT changes. During the 3 months following the initiation of the first WMT course, antiseizure medications remained unchanged from baseline, providing a medication-stable observation window.

    Results: Within this window, monthly seizure burden decreased from 32 seizures/month at baseline to 16, 23, and 20 seizures/month at 1, 2, and 3 months, respectively. These changes were accompanied by improvements in cognition, sleep, gastrointestinal symptoms, global neurological function, psychiatric symptoms, quality of life, and caregiver burden.

    Conclusion: The single-patient observations suggest that WMT is temporally associated with early multidimensional clinical improvement and gut ecosystem remodeling in chronic-phase FIRES. The findings are exploratory and require validation in larger medication-controlled cohorts.

  • CASE SERIES
    Mengyu Huang, Yaping Liu, Hong Lu, Weihong Wang, Huiying Gao, Junlan Qiu, Yan Jin, Qian Ren
    2026, 1(3): 116-123. https://doi.org/10.1002/mmr3.70011

    Background: Immune-mediated colitis is an adverse effect of therapy with immune checkpoint inhibitors (ICIs). This study aims to evaluate the efficacy and safety of washed microbiota transplantation (WMT) in patients with ICI-associated colitis.

    Methods: This multi-center, retrospective case series included six patients with ICI-associated colitis who received WMT between September 2023 and December 2025. Cases were voluntarily contributed by each center where data were available and complete and thus do not represent a complete consecutive case series.

    Results: In total, 6 patients with ICI-associated colitis were included for analysis. Among all patients, 5 were male and 1 was female, with an age range of 46–71 years (mean 59.5 years). ICI-associated colitis occurred between cycle 1 and cycle 6 of ICI treatments. According to Common Terminology Criteria for Adverse Events (CTCAE) grading, 3 patients had grade 2, 2 had grade 3, and 1 had grade 4 colitis. Endoscopic findings included mucosal hyperemia, edema, erosion, or shallow ulcers; pathology predominantly showed chronic active inflammation. All 6 patients (100%) achieved clinical remission, with time to remission ranging from 3 to 7 days (4 patients within 5 days). At the last follow-up, all patients had recovered to 1–2 bowel movements per day with formed stools, and no clinical recurrence of colitis was observed during follow-up. No tumor progression occurred during or after WMT. Five patients subsequently resumed or continued anti-tumor therapy. No WMT-related adverse events were observed.

    Conclusion: WMT is associated with rapid clinical remission of ICI-associated colitis with a favorable safety profile, and may create conditions for the resumption of anti-tumor therapy. It also shows salvage therapy potential for severe, steroid-refractory cases, although further prospective studies are needed.

  • PERSPECTIVE
    Xiaoqian Zhang
    2026, 1(3): 124-126. https://doi.org/10.1002/mmr3.70012