{
  "abstract": "Background Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract with an unclear etiology. Its pathogenesis involves genetic susceptibility, impaired intestinal barrier function, dysregulated immune responses, and gut microbiota dysbiosis. In our previous cohort study of Crohn’s disease (CD) patients receiving ustekinumab (UST), our team observed that responders exhibited a significantly higher abundance of the genus Megamonas, particularly Megamonas funiformis. Although M. funiformis has been reported as a characteristic taxon in Asian populations, its functional role in the gut microbiome and its association with IBD remain unclear. This study aimed to investigate the potential role and underlying mechanisms of M. funiformis in IBD.Methods Intestinal mucosal samples, including inflamed and non-inflamed regions, were collected from three CD patients. Fluorescence in situ hybridization (FISH) was performed to determine the spatial distribution of M. funiformis. In addition, two M. funiformis strains (MF4605 and MF4606) were isolated from fecal samples of healthy volunteers. A dextran sulfate sodium (DSS)-induced acute colitis mouse model was established to evaluate their effects on intestinal inflammation and gut microbiota composition. Whole-genome sequencing and comparative genomic analyses were conducted to identify genetic differences between the strains, followed by targeted Q300 metabolomics to characterize their metabolic profiles.Results FISH analysis revealed that M. funiformis was significantly enriched in the inflamed mucosa of CD patients (IDDF2026-ABS-0531 Figure 1(A) M funiformis alleviates DSS-induced colitis and modulates gut microbiota composition). In the DSS-induced colitis model, MF4606, but not MF4605, markedly alleviated colitis severity (IDDF2026-ABS-0531 Figure 1(B-G) M funiformis alleviates DSS-induced colitis and modulates gut microbiota composition) and reshaped gut microbiota composition, characterized by enrichment of Akkermansia and increased abundance of beneficial bacteria (IDDF2026-ABS-0531 Figure 1(H-J) M funiformis alleviates DSS-induced colitis and modulates gut microbiota composition). Comparative genomic analysis showed that MF4606 lacked key sialic acid metabolism genes (nanA and nanE). Consistently, targeted metabolomic analysis demonstrated a significant accumulation of N-acetylneuraminic acid (sialic acid) in the culture supernatant of MF4606 (IDDF2026-ABS-0531 Figure 2(A-C) Genomic features and metabolite comparison of MF4605 and MF4606).Conclusions These findings demonstrate that M. funiformis is enriched in the inflamed mucosa of CD patients and exhibits strain-specific functional heterogeneity. MF4606 exerts anti-inflammatory effects and modulates gut microbiota, potentially through altered sialic acid metabolism. This study provides new insights into the role of Megamonas in IBD and highlights its potential as a microbiota-based therapeutic target.Abstract IDDF2026-ABS-0531 Figure 1Abstract IDDF2026-ABS-0531 Figure 2",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, China"
      ],
      "name": "Minna Zhang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, China"
      ],
      "name": "Honggang Wang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, China"
      ],
      "name": "Xiaozhong Yang"
    },
    {
      "affiliations": [
        "Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, China"
      ],
      "name": "Pan Li"
    }
  ],
  "title": "IDDF2026-ABS-0531 N-acetylneuraminic acid metabolism-driven functional heterogeneity of megamonas funiformis in colitis",
  "uid": "f29a8534-8bb2-5932-ad46-6932548ddc0c"
}