{
  "abstract": "Background Cognitive impairment is a common accompanying symptom in pediatric neuropsychiatric disorders and can seriously affect learning ability and quality of life. Increasing evidence has linked the gut microbiota to cognition. We aimed to evaluate whether washed microbiota transplantation (WMT) could improve cognitive function in children with neuropsychiatric disorders and to explore the potential mechanisms underlying this effect.Methods Children with neuropsychiatric disorders undergoing WMT, including those with epilepsy, attention-deficit/hyperactivity disorder, and autism spectrum disorder, were evaluated for cognitive changes before and after treatment using the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales. Exploratory mechanistic analyses were further performed in children with epilepsy using metagenomic sequencing of paired fecal samples, metabolomic profiling of paired serum and urine samples, and intestinal mucosal transcriptomic analysis. In addition, fecal microbiota from epilepsy patients with marked cognitive impairment was transplanted into mice.Results Overall, cognitive function improved after WMT in the pediatric neuropsychiatric cohort (N = 74) ( IDDF2026-ABS-0421 Figure 1(A-E) Cognitive and seizure outcomes after washed microbiota transplantation in children with epilepsy). In the epilepsy subgroup, 15 of 17 children (88.2%) had baseline cognitive decline, and the 3-month cognitive response rate was 47.1%, with response defined as a CGI-I score ≤2 (IDDF2026-ABS-0421 Figure 1(F,G) Cognitive and seizure outcomes after washed microbiota transplantation in children with epilepsy). Seizure frequency was also reduced, with response rates of 35.3% at 1 month and 64.7% at 3 months (IDDF2026-ABS-0421 Figure 1(H-J) Cognitive and seizure outcomes after washed microbiota transplantation in children with epilepsy). Metagenomic analysis showed increased abundance of Roseburia intestinalis after WMT, which was significantly associated with cognitive improvement (IDDF2026-ABS-0421 Figure 2(A,B) Multi-omics analysis identifies Roseburia intestinalis, ceramide remodeling, and GRM2-related). Metabolomic analysis showed reduced ceramide levels together with increased sphingomyelin and SHexCer levels (IDDF2026-ABS-0421 Figure 2(C-E) Multi-omics analysis identifies Roseburia intestinalis, ceramide remodeling, and GRM2-related). Transcriptomic analysis indicated upregulation of GRM2 after treatment (IDDF2026-ABS-0421 Figure 2(F,G) Multi-omics analysis identifies Roseburia intestinalis, ceramide remodeling, and GRM2-related). In recipient mice, microbiota from cognitively impaired epilepsy patients induced microglial activation, neuroinflammation, and cognitive decline (IDDF2026-ABS-0421 Figure 3. Microbiota from cognitively impaired epilepsy patients induces cognitive decline, microglial, IDDF2026-ABS-0421 Figure 4. Gut microbiota dysbiosis and intestinal GRM2 downregulation in patients with epilepsy).Conclusions WMT may improve cognitive function in children with neuropsychiatric disorders. Ceramide-related lipid remodeling and GRM2-related neural signaling may represent two potential mechanistic clues.Abstract IDDF2026-ABS-0421 Figure 1Abstract IDDF2026-ABS-0421 Figure 2Abstract IDDF2026-ABS-0421 Figure 3Abstract IDDF2026-ABS-0421 Figure 4",
  "authors": [
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Qianqian Li"
    },
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Faming Zhang"
    },
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Xiao Ding"
    },
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Zulun Zhang"
    },
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Siyu Chen"
    },
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Xianglu Wang"
    },
    {
      "affiliations": [
        "The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Jianyu Wu"
    }
  ],
  "title": "IDDF2026-ABS-0421 Washed microbiota transplantation improves cognitive function in children with neuropsychiatric disorders",
  "uid": "1aa3ee5a-6dfc-5d29-bdcd-ee144934f47d"
}