Washed Microbiota Transplantation Improves Chronic-Phase Febrile Infection-Related Epilepsy Syndrome: The First Case Report With Long-Term Follow-Up and Integrated Multi-Omics Analysis

Abstract

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.

Graphical abstract

Keywords

epilepsy / febrile infection-related epilepsy syndrome / fecal microbiota transplantation / gut-brain axis / metagenomic sequencing / urinary metabolomics

1 Introduction

Febrile infection-related epilepsy syndrome (FIRES) is a rare and devastating epileptic encephalopathy within the new-onset refractory status epilepticus (NORSE) spectrum. It is defined by a preceding febrile infection occurring between 24 h and 2 weeks before refractory status epilepticus in individuals without prior active epilepsy or an identifiable acute structural, toxic, or metabolic cause [1]. FIRES typically affects previously healthy children and adolescents. It can evolve from an acute catastrophic seizure disorder into a chronic condition marked by drug-resistant epilepsy, cognitive impairment, behavioral and psychiatric symptoms, and long-term functional disability [2–5]. International consensus recommendations have improved diagnosis and acute management, including antiseizure medications (ASMs), anesthetic therapy, immunotherapy, and ketogenic diet (KD). However, effective strategies for chronic-phase FIRES and its nonseizure comorbidities remain limited [6, 7]. Recent expert commentary further emphasizes that NORSE/FIRES care requires coordinated multidisciplinary management across the acute and chronic phases, with attention to survivorship, functional recovery, family support, and long-term research collaboration [8].

KD is an established nonpharmacological therapy for FIRES and drug-resistant epilepsy, but its clinical implementation can be limited by delayed onset, dietary burden, and variable tolerability [6, 9]. Clinical and mechanistic evidence indicates that KD may exert antiseizure effects through metabolic reprogramming, mitochondrial support, neuroinflammation modulation, neurotransmitter regulation, and changes in gut microbial composition and function [9]. Experimental and translational studies further support a causal role of gut microbiota in mediating KD-related seizure protection [10, 11]. Beyond dietary modulation, direct microbiota-based interventions have shown preliminary value in gut-brain axis-related conditions, including fecal microbiota transplantation (FMT), as suggested by open-label studies in patients with epilepsy and children with autism spectrum disorder [12–15]. These findings suggest that gut microbiota may influence seizure susceptibility and neurological comorbidities through a network of immune, metabolic, endocrine, neural, and barrier-related pathways [16, 17].

Washed microbiota transplantation (WMT) is an optimized form of FMT that incorporates automated microbiota purification, repeated centrifugation, and washing procedures. These steps are intended to reduce fecal impurities, improve preparation consistency, enable quantitative quality control, and enhance clinical safety [18–21]. Given the persistent unmet need in chronic-phase FIRES, microbiota-targeted intervention may be particularly relevant when seizures are accompanied by a burden of cognitive, sleep, gastrointestinal, and neuropsychiatric morbidities. Here, we describe a 17-year-old adolescent female patient with chronic-phase FIRES who received two courses of WMT. By integrating 36-month clinical follow-up with metagenomic sequencing, urinary metabolomics, and 16S rRNA sequencing, this brief report examines the temporal association between WMT, multidimensional clinical improvement, and taxonomic, functional, and metabolic features of gut microbiota remodeling.

2 Patients and Methods

2.1 Clinical Characteristics of the Patient

A 17-year-old adolescent female patient with chronic-phase FIRES was admitted to the Second Affiliated Hospital of Nanjing Medical University in July 2019 for WMT. She had been previously healthy until April 2016, when unexplained high fever was followed by generalized tonic-clonic seizures and refractory status epilepticus. Extensive evaluation did not identify a definite infectious, autoimmune, metabolic, structural, or genetic cause. After the acute phase, she had chronic drug-resistant epilepsy, cognitive and memory impairment, behavioral abnormalities, sleep disturbance, and constipation. Acute-phase details are summarized in Figure 1.

Before WMT, seizure types included asymmetric tonic seizures, unilateral facial or limb clonic seizures with secondary bilateral tonic-clonic seizures, and episodes of behavioral arrest with oro-facial automatisms. The baseline seizure burden was 32 seizures/month, calculated from the 3 months before WMT. Baseline ASMs were topiramate 50 mg twice daily, oxcarbazepine 600 mg twice daily, lacosamide 150 mg twice daily, and lamotrigine 25 mg twice daily.

2.2 WMT Procedure

Healthy donors were obtained from the China Microbiota Transplantation System and screened according to standardized donor-screening criteria [20]. Fresh stool from qualified donors was processed in a standardized laboratory using microfiltration and repeated centrifugation-based enrichment with GenFMTer (FMT Medical, Nanjing, China) within 1 h. One unit (U) of the final precipitated microbiota, the basic therapeutic unit for clinical use, is defined as 10 mL containing no less than 1.0 × 10¹⁰ colony-forming units (CFU) of viable anaerobic bacteria [22, 23].The patient received two courses of WMT via the colonic transendoscopic enteral tube in 2019. Each course consisted of three infusions of freshly prepared washed microbiota suspension derived from screened healthy donors. The patient continued the same ASM regimen as before WMT, unless medication changes were clinically required.

2.3 Clinical Outcome Assessment

Monthly seizure frequency was recorded for 36 months after the first WMT course. Seizure severity, psychiatric symptoms, sleep quality, gastrointestinal symptoms, quality of life, cognition, and global neurological function were assessed using the Liverpool Seizure Severity Scale (LSSS), Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index (PSQI), Gastrointestinal Symptom Rating Scale (GSRS), Quality of Life in Epilepsy Inventory-10 (QOLIE-10), Mini-Mental State Examination (MMSE), and Pediatric Cerebral Performance Category (PCPC), respectively. Caregiver anxiety, depressive symptoms, and care burden were evaluated using the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Zarit Burden Interview (ZBI), respectively. Assessments were performed before WMT and at 1, 3, 6, 12, and 36 months after the first WMT course.

The WMT period and the first 3 months after WMT were considered the primary medication-stable observation window because the ASM regimen remained unchanged from baseline during this period. Long-term clinical trajectories over 36 months were described separately and interpreted in the context of subsequent treatment modifications. An additional clinical status update was obtained at the most recent clinical contact in May 2026, without repeat scale-based assessment.

2.4 Metagenomic Sequencing

Fecal samples were collected from the patient before WMT and at 1 week, 1 month, and 3 months after the first WMT course. These samples were labeled pre-WMT, 1 week, 1 month, and 3 months, respectively. The corresponding donor for course 1 was labeled Donor 1. Fecal samples were transported to the laboratory within 2 h of collection, immediately aliquoted, and stored at −80°C for long-term preservation.

DNA libraries were prepared using the Illumina NEBNext Ultra DNA Library Prep Kit and sequenced on an Illumina PE150 platform (Beijing Microread Genetics Co. Ltd, Beijing, China). Raw reads were filtered using Fastp v0.23.2, and host-derived reads were removed using BWA v0.7.17 and Samtools v1.9. Taxonomic profiling was performed using MetaPhlAn v3.0.14, and functional profiling was performed using HUMAnN3 with MetaCyc pathway annotation [24]. Shannon diversity, Bray-Curtis dissimilarity, donor-distance analysis, and principal coordinates analysis (PCoA) were used descriptively to summarize taxonomic and functional profiles. Top changed species and pathways were visualized as row z-score heatmaps.

2.5 Urinary Metabolomics

Urine samples collected before and after WMT were subjected to untargeted metabolomic profiling using the NGM2pro platform (Shanghai Biotree Biomedical Technology Co. Ltd., Shanghai, China). Liquid chromatography-mass spectrometry was performed on an Orbitrap Exploris 120 mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA) according to the service provider's standard operating procedures. Log₂ fold changes were calculated for post-WMT versus pre-WMT urinary metabolites. Mappings were labeled as direct/close when the metabolite was the named product or a closely related derivative, or as network-context when the link was broader or involved host metabolism. No statistical testing was performed because this was a descriptive single-patient analysis.

2.6 16S rRNA Sequencing

The 16S rRNA sequencing was performed by TinyGene Bio-Tech (Shanghai) Co. Ltd. (Shanghai, China) as a supplementary analysis to characterize longitudinal gut microbiota compositional remodeling across two WMT courses and up to 6 months. The V3–V4 region of the bacterial 16S rRNA gene was amplified and sequenced. Samples included Donor 1, Donor 2, pre-WMT, 1 week_1st, 1 month, 3 months, 1 week_2nd, and 6 months. Paired-end reads were demultiplexed by barcode, quality-filtered using Trimmomatic v0.38, primer-trimmed using cutadapt v1.16, merged using FLASH v1.2.11, and optimized using mothur v1.39.5. Operational taxonomic units (OTUs) were clustered at 97% sequence similarity using USEARCH v8.1.1861/UPARSE, and chimeric sequences were removed using UCHIME. Taxonomic annotation was performed using mothur against the SILVA database with a confidence threshold of 0.6. For visualization, genus-level Bray-Curtis dissimilarity was used for PCoA, and phylum-level relative abundances were summarized with the Firmicutes/Bacteroidetes ratio.

3 Results

3.1 WMT Is Associated With Early Multidimensional Clinical Improvement and Sustained Long-Term Trajectories

Before WMT, the patient had chronic-phase FIRES with frequent drug-resistant seizures despite multiple ASMs. Baseline seizure burden was 32 seizures/month, calculated from the 3 months preceding WMT. During WMT course 1 and the first 3 months after WMT, the ASM regimen remained unchanged, providing a medication-stable observation window for early clinical evaluation (Figure 2A,B). Within this period, seizure burden decreased to 16, 23, and 20 seizures/month at 1, 2, and 3 months, respectively (Figure 2A). Monthly seizure response analysis showed heterogeneous but overall favorable response patterns, with 11 months (30.6%) achieving ≥ 50% reduction, 15 months (41.7%) achieving 25% to < 50% reduction, 8 months (22.2%) showing > 0% to < 25% reduction, and 2 months (5.6%) showing no change (Figure 3C).

Clinical changes extended beyond seizure reduction. At 1 month and 3 months, MMSE increased from 9 to 15 and 21, respectively; PSQI decreased from 15 to 3 and 1, respectively; GSRS decreased from 9 to 1 and 0, respectively; and PCPC improved from severe disability to moderate disability (Figure 3A). In parallel, LSSS, PANSS, and QOLIE-10 also showed favorable longitudinal trajectories, while caregiver burden (ZBI), anxiety (HAMA), and depression (HAMD) also decreased during follow-up (Figure 3A, B). At 36 months, most clinical improvements were maintained, although interpretation was limited by subsequent lamotrigine up-titration at month 5, ASM regimen modification at month 10, and deep brain stimulation (DBS) at month 23 (Figure 2B). No WMT-related adverse events were observed.

At the most recent clinical contact in May 2026, nearly 7 years after the first WMT course, the patient remained in a favorable overall clinical condition, with sustained improvements in cognition, sleep, gastrointestinal symptoms, psychiatric symptoms, neurological function, and quality of life, except for persistent seizures.

3.2 WMT Is Accompanied by Increased Gut Microbiota Diversity and Ecosystem Remodeling

Metagenomic sequencing showed post-WMT remodeling of the gut microbiota at both taxonomic and functional levels (Figure 4). Taxonomic Shannon diversity increased from 3.32 before WMT to 3.87 at 1 week after WMT, and then remained above baseline at 1 month and 3 months (Figure 4A). Functional Shannon diversity also increased from 4.85 before WMT to 5.10 at 1 week, remained elevated at 1 month, and was still above baseline at 3 months (Figure 4A). Bray-Curtis distance analysis further showed dynamic shifts from the pre-WMT profile and variable proximity to the Donor 1 mean profile (Figure 4B). Donor 1 was represented by a constructed mean profile generated from three samples from the same donor. At 1 week, 1 month, and 3 months, taxonomic distances to the Donor 1 mean profile were 0.47, 0.53, and 0.46, respectively, whereas functional distances were lower at 0.08, 0.10, and 0.09, respectively. PCoA showed longitudinal restructuring of recipient profiles at both the taxonomic and functional levels (Figure 4C,D). Together, these descriptive findings indicate post-WMT recipient microbiota restructuring, with smaller donor distances in functional feature space than in taxonomic composition.

3.3 Microbial Species and Functional Pathway Remodeling After WMT

Species-level profiles changed dynamically after WMT (Figure 5A). The relative abundance of Faecalibacterium prausnitzii increased from 0.09 at pre-WMT to 10.75, 7.39, and 13.63 at 1 week, 1 month, and 3 months, respectively. Functional pathway profiles also changed after WMT (Figure 5B), including pathways related to branched-chain amino acid biosynthesis, carbohydrate utilization, one-carbon metabolism, vitamin B₆ metabolism, and nucleotide biosynthesis. The heatmaps show temporal and donor-referenced variation, without implying uniform enrichment across all displayed features. In the 3-month versus pre-WMT comparison, L-isoleucine biosynthesis III increased and pyridoxal 5′-phosphate biosynthesis I decreased, with log₂ fold changes of +1.99 and −1.56, respectively.

3.4 Exploratory Mapping Identifies Directionally Associated Pathway-Metabolite Candidates

A post-hoc biochemical direction comparison identified several pathway-metabolite candidates (Figure 5C). The clearest direct or closely related pairs were increased L-isoleucine biosynthesis III (+1.99) with the leucine/isoleucine feature (+0.66), decreased pyridoxal 5′-phosphate biosynthesis I (−1.56) with pyridoxal (−2.92), and increased D-galactose degradation V (+1.77) with galactitol (+1.07). Broader network-context pairs included branched-chain amino acid biosynthesis with isovalerylcarnitine, N¹⁰-formyl-tetrahydrofolate biosynthesis with choline, and L-ornithine biosynthesis with glutamate or proline.

3.5 16S rRNA Sequencing Supports Longitudinal Compositional Remodeling

16S rRNA sequencing across two WMT courses supported longitudinal compositional restructuring of the gut microbiota (Figure 6A). Genus-level PCoA showed that post-WMT samples shifted away from the baseline sample with temporal variation. At the phylum level, dominant taxa fluctuated over time, accompanied by an overall increase in the Firmicutes/Bacteroidetes ratio during follow-up compared with baseline (Figure 6B). These results were used as supplementary evidence of compositional remodeling and were not interpreted as functional changes.

4 Discussion

This brief report describes a 17-year-old adolescent female patient with chronic-phase FIRES who showed multidimensional clinical improvement after two courses of WMT, accompanied by gut ecosystem remodeling and exploratory pathway-metabolite direction comparison. The clinical value of this case lies in the disease context and the breadth of the observed improvement. Chronic-phase FIRES is difficult to manage, and long-term outcomes extend beyond seizures to cognition, behavior, psychiatric symptoms, function, quality of life, and family burden [2–4, 25]. In this case, improvement was observed in seizure burden, seizure severity, cognition, sleep, psychiatric symptoms, gastrointestinal symptoms, neurological function, and caregiver burden. The broad outcome panel remains relevant because chronic FIRES affects both patients and families.

The strongest clinical signal occurred during the first WMT course and the subsequent 3-month period, when the ASM regimen remained unchanged from baseline. Stable ASM exposure reduced confounding from concurrent medication changes but did not exclude spontaneous fluctuation, regression to the mean, measurement effects, or other aspects of care. The 36-month follow-up showed favorable trajectories across several domains. However, later lamotrigine up-titration, ASM changes, and DBS limit causal interpretation of the long-term course. Thus, this case supports a temporal association between WMT and early multidimensional change, rather than proof of a treatment effect.

Recent NORSE/FIRES studies emphasize that survivors and families face persistent challenges related to seizures, neuropsychological impairment, behavioral changes, loss of independence, care coordination, and quality of life [8, 26, 27]. In this case, caregiver anxiety, depressive symptoms, and ZBI scores improved after WMT. Although these changes cannot be attributed solely to WMT, they suggest that future studies should include caregiver-centered endpoints such as anxiety, depressive symptoms, care burden, and family functioning, rather than relying only on seizure counts.

The biological plausibility of WMT is supported by growing evidence that gut microbiota can influence neurological function through immune, metabolic, barrier-related, neural, and endocrine pathways [16, 17]. This is particularly relevant to epilepsy because KD, an accepted therapy for FIRES and drug-resistant epilepsy, can reshape gut microbiota and its antiseizure effects can be microbiota-dependent in experimental and translational studies [9–11]. Direct microbiota-based interventions have also shown preliminary signals in gut-brain axis-related disorders, including epilepsy, autism spectrum disorder, Parkinson's disease, Alzheimer's disease models, and amyotrophic lateral sclerosis (ALS), although the evidence remains early and heterogeneous [12–14, 28–31]. These studies do not prove efficacy of WMT in FIRES. Rather, they support further testing of microbiota-targeted interventions in carefully designed studies of refractory neurological conditions.

After WMT, taxonomic diversity increased early and remained above baseline at 1 month and 3 months, whereas functional diversity also remained above baseline. F. prausnitzii was consistently more abundant after WMT, which is a recognized butyrate-producing species with anti-inflammatory properties [32–34]. A notable finding was that microbial functional profiles showed smaller Bray-Curtis distances to the Donor 1 mean profile than taxonomic composition. This observation is consistent with our recent WMT cohort study in patients with epilepsy, which similarly found that post-WMT microbial functional profiles became more donor-like than taxonomic composition [15]. Replication of the present donor-distance pattern requires comparable donor-recipient sampling in larger cohorts.

The post-hoc pathway-metabolite direction comparison generated several biologically plausible candidates but did not independently confirm microbial functional changes. The most direct or closely related aligned pairs involved L-isoleucine biosynthesis III with an unresolved urinary leucine/isoleucine feature, pyridoxal 5′-phosphate biosynthesis I with pyridoxal, and D-galactose degradation V with galactitol. Additional associations, including branched-chain amino acid biosynthesis with isovalerylcarnitine, one-carbon metabolism with choline, and ornithine biosynthesis with glutamate or proline, represented broader network-context relationships that may involve host as well as microbial metabolism. These candidate networks are relevant to amino acid, cofactor, and one-carbon metabolism in the nervous system [35–38]. Because the mapping was selected post-hoc and was based on only one pre-WMT and one post-WMT urine sample, these observations should be considered hypothesis-generating rather than evidence of correlation, microbial origin, pathway flux, or brain-level metabolic change.

This brief report has several limitations. It describes a single-patient observation without a control group. Larger medication-controlled FIRES cohorts with repeated donor-recipient metagenomic sequencing, metabolomics, inflammatory markers, electroencephalography, neuropsychological assessment, and caregiver-centered outcomes are needed.

In conclusion, WMT is associated with temporally aligned multidimensional improvement in chronic-phase FIRES during a medication-stable window. These findings support further investigation of microbiota-targeted strategies as adjunctive approaches for chronic-phase FIRES and other refractory epilepsy-related conditions.

References

[1] L. J. Hirsch, N. Gaspard, A. van Baalen, et al., “Proposed Consensus Definitions for New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and Related Conditions,” Epilepsia 59, no. 4 (2018): 739–744.

[2] U. Kramer, C. S. Chi, K. L. Lin, et al., “Febrile Infection-Related Epilepsy Syndrome (FIRES): Pathogenesis, Treatment, and Outcome: A Multicenter Study on 77 Children,” Epilepsia 52, no. 11 (2011): 1956–1965.

[3] K. B. Howell, K. Katanyuwong, M. T. Mackay, et al., “Long-Term Follow-Up of Febrile Infection-Related Epilepsy Syndrome,” Epilepsia 53, no. 1 (2012): 101–110.

[4] A. Shrestha, E. L. Wood, G. Berrios-Siervo, et al., “Long-Term Neuropsychological Outcomes in Children With Febrile Infection-Related Epilepsy Syndrome (FIRES) Treated With Anakinra,” Frontiers in Neurology 14 (2023): 1100551.

[5] S. K. Lam, W. Y. Lu, W. C. Weng, P. C. Fan, and W. T. Lee, “The Short-Term and Long-Term Outcome of Febrile Infection-Related Epilepsy Syndrome in Children,” Epilepsy and Behavior 95 (2019): 117–123.

[6] R. Wickstrom, O. Taraschenko, R. Dilena, et al., “International Consensus Recommendations for Management of New Onset Refractory Status Epilepticus (NORSE) Including Febrile Infection-Related Epilepsy Syndrome (FIRES): Summary and Clinical Tools,” Epilepsia 63, no. 11 (2022): 2827–2839.

[7] X. Yan, J. He, M. Cheng, S. Hong, L. Jiang, and W. Han, “Efficacy Differences Between Tocilizumab and Ketogenic Diet During Acute Phase of Febrile Infection-Related Epilepsy Syndrome in Children: A Retrospective Cohort Study,” Epilepsy and Behavior 177 (2026): 110898.

[8] K. Eschbach, K. S. Fisher, H. A. Haider, et al., “New-Onset Refractory Status Epilepticus/Febrile Infection-Related Epilepsy Syndrome Centers of Excellence: A Framework for Coordinated Care, Research, and Improved Outcomes,” Epilepsia (2026), https://doi.org/10.1002/epi.70338.

[9] A. G. Figueroa, C. N. Joshi, and M. N. Patel, “From Clinical Practice to Mechanistic Insights in Ketogenic Diets for Epilepsy,” Lancet Neurology 25, no. 5 (2026): 519–532.

[10] C. A. Olson, H. E. Vuong, J. M. Yano, Q. Y. Liang, D. J. Nusbaum, and E. Y. Hsiao, “The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet,” Cell 173, no. 7 (2018): 1728–1741.

[11] G. R. Lum, S. M. Ha, C. A. Olson, et al., “Ketogenic Diet Therapy for Pediatric Epilepsy Is Associated With Alterations in the Human Gut Microbiome That Confer Seizure Resistance in Mice,” Cell Reports 42, no. 12 (2023): 113521.

[12] Z. He, B. T. Cui, T. Zhang, et al., “Fecal Microbiota Transplantation Cured Epilepsy in a Case With Crohn's Disease: The First Report,” World Journal of Gastroenterology 23, no. 19 (2017): 3565–3568.

[13] D. W. Kang, J. B. Adams, A. C. Gregory, et al., “Microbiota Transfer Therapy Alters Gut Ecosystem and Improves Gastrointestinal and Autism Symptoms: An Open-Label Study,” Microbiome 5, no. 1 (2017): 10.

[14] D. W. Kang, J. B. Adams, D. M. Coleman, et al., “Long-Term Benefit of Microbiota Transfer Therapy on Autism Symptoms and Gut Microbiota,” Scientific Reports 9, no. 1 (2019): 5821.

[15] Q. Li, R. He, X. Wang, et al., “Akkermansia muciniphila Enhances Washed Microbiota Transplantation in the Treatment of Epilepsy,” Chinese Medical Journal 139, no. 17 (2026): 2608–2620.

[16] J. F. Cryan, K. J. O'Riordan, C. S. M. Cowan, et al., “The Microbiota-Gut-Brain Axis,” Physiological Reviews 99, no. 4 (2019): 1877–2013.

[17] K. G. Margolis, J. F. Cryan, and E. A. Mayer, “The Microbiota-Gut-Brain Axis: From Motility to Mood,” Gastroenterology 160, no. 5 (2021): 1486–1501.

[18] W. Wang, Y. Yu, R. Wang, et al., “Holdemanella biformis Augments Washed Microbiota Transplantation for the Treatment of Radiation Enteritis,” Gut 75, no. 2 (2026): 289–301.

[19] T. Zhang, G. Lu, Z. Zhao, et al., “Washed Microbiota Transplantation vs. Manual Fecal Microbiota Transplantation: Clinical Findings, Animal Studies and in Vitro Screening,” Protein & Cell 11, no. 4 (2020): 251–266.

[20] Fecal Microbiota Transplantation-standardization Study Group, “Nanjing Consensus on Methodology of Washed Microbiota Transplantation,” Chinese Medical Journal 133, no. 19 (2020): 2330–2332.

[21] Q. Li, Y. Liu, Z. Zhang, S. Zhang, X. Ding, and F. Zhang, “Washed Microbiota Transplantation Improves the Sleep Quality in Patients With Inflammatory Bowel Disease,” Nature and Science of Sleep 16 (2024): 1141–1152.

[22] F. Zhang, S. H. Wong, G. Lu, et al., “Nanjing Consensus II on Washed Microbiota Transplantation: Statements From the CHINAGUT Conference,” Microbiota Medicine Research 1, no. 2 (2026): 45–62.

[23] Q. Li, X. Ding, K. Liu, et al., “Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes,” Clinical and Translational Gastroenterology 11, no. 8 (2020): e00224.

[24] E. A. Franzosa, L. J. McIver, G. Rahnavard, et al., “Species-Level Functional Profiling of Metagenomes and Metatranscriptomes,” Nature Methods 15, no. 11 (2018): 962–968.

[25] P. H. Espino, K. Eschbach, L. J. Blank, et al., “New Onset Refractory Status Epilepticus: Long-Term Outcomes Beyond Seizures,” Epilepsia 66, no. 4 (2025): 988–1005.

[26] R. Farias-Moeller, A. Wood, R. Sawdy, J. Koop, K. Olson, and A. van Baalen, “Parental Perception of FIRES Outcomes, Emotional States, and Social Media Usage,” Epilepsia Open 6, no. 3 (2021): 539–547.

[27] K. Eschbach, J. Reedy, T. Gofton, et al., “Navigating Life After New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES): Insights From Caregiver and Patient Interviews,” Epilepsy and Behavior 163 (2025): 110236.

[28] F. Scheperjans, R. Levo, B. Bosch, et al., “Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial,” JAMA Neurology 81, no. 9 (2024): 925–938.

[29] J. Sun, J. Xu, Y. Ling, et al., “Fecal Microbiota Transplantation Alleviated Alzheimer's Disease-Like Pathogenesis in APP/PS1 Transgenic Mice,” Translational Psychiatry 9, no. 1 (2019): 189.

[30] J. Yan, H. Chen, Y. Zhang, et al., “Fecal Microbiota Transplantation Significantly Improved Respiratory Failure of Amyotrophic Lateral Sclerosis,” Gut Microbes 16, no. 1 (2024): 2353396.

[31] R. Feng, Q. Zhu, A. Wang, et al., “Effect of Fecal Microbiota Transplantation on Patients With Sporadic Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial,” BMC Medicine 22, no. 1 (2024): 566.

[32] M. Lenoir, R. Martín, E. Torres-Maravilla, et al., “Butyrate Mediates Anti-Inflammatory Effects of Faecalibacterium prausnitzii in Intestinal Epithelial Cells Through Dact3,” Gut Microbes 12, no. 1 (2020): 1–16.

[33] B. Dalile, L. Van Oudenhove, B. Vervliet, and K. Verbeke, “The Role of Short-Chain Fatty Acids in Microbiota-Gut-Brain Communication,” Nature Reviews Gastroenterology & Hepatology 16, no. 8 (2019): 461–478.

[34] Y. P. Silva, A. Bernardi, and R. L. Frozza, “The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication,” Frontiers in Endocrinology 11 (2020): 25.

[35] J. M. Rho and D. Boison, “The Metabolic Basis of Epilepsy,” Nature Reviews Neurology 18, no. 6 (2022): 333–347.

[36] S. Friso, S. Udali, D. De Santis, and S. W. Choi, “One-Carbon Metabolism and Epigenetics,” Molecular Aspects of Medicine 54 (2017): 28–36.

[37] D. Erny, A. L. Hrabě de Angelis, D. Jaitin, et al., “Host Microbiota Constantly Control Maturation and Function of Microglia in the CNS,” Nature Neuroscience 18, no. 7 (2015): 965–977.

[38] M. Yudkoff, “Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids and Ketoacids in the CNS,” Neurochemical Research 42, no. 1 (2017): 10–18.

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