{
  "abstract": "Background Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by persistent mucosal inflammation. The gut microbiota has emerged as a central regulator of intestinal homeostasis. Modulation of the microbiome through Fecal Microbiota Transplantation (FMT) shows clinical potential. Unfortunately, donor variability often leads to inconsistent treatment outcomes. Faecalibacterium prausnitzii is a keystone species in the healthy human gut. Its depletion strongly correlates with IBD severity and recurrence. This protective effect primarily depends on the Microbial Anti-Inflammatory Molecule (MAM). MAM inhibits the NF-κB pathway and suppresses proinflammatory cytokines such as TNF-α. However, genetic diversity among F. prausnitzii strains causes significant variations in anti-inflammatory activity. We systematically screened MAM variants to identify high-potency strains for standardized clinical use.Methods Genomic sequences of 71 Faecalibacterium strains were retrieved from the NCBI database. We identified the genes encoding the MAM protein and translated them into amino acid sequences. Maximum Likelihood evolutionary analysis was then performed using MEGA-X software. This analysis defined distinct phylogenetic lineages. We cloned codon-optimized MAM sequences into pcDNA3.1 expression vectors. These constructs were subsequently co-transfected with NF-κB or TNF-α luciferase reporter plasmids into HCT116 cells to quantify their inhibitory effects.Results Phylogenetic analysis of MAM sequences revealed at least seven distinct lineages (Lineages A–G) ( IDDF2026-ABS-0372 Figure 1. Phylogenetic tree of MAM from Faecalibacterium strains. Maximum Likelihood phylogenetic tree of MAM amino acid sequences). Initial screening showed that MAM from Lineage A (strain M21/2) exhibited the strongest anti-inflammatory effect (IDDF2026-ABS-0372 Figure 2. Anti-inflammatory activity of MAM derived from representative strains of each lineage). Further screening within Lineage A identified the MAM from strain CNCM I 4644 as the most potent variant (IDDF2026-ABS-0372 Figure 3. Anti-inflammatory activity of MAM derived from strains within lineage A). CNCM I 4644 MAM maintained robust activity even at very low doses. It achieved over 90% inhibition of NF-κB and TNF-α signaling (IDDF2026-ABS-0372 Figure 4. Dose-response analysis of MAM derived from strain CNCM I 4644). In contrast, the reference strain A2-165 yielded only 50% to 56% inhibition at equivalent doses. These results demonstrate the superior efficacy of the CNCM I 4644 strain.Conclusions Phylogenetic screening of MAM sequences effectively identifies therapeutically superior F. prausnitzii strains. The MAM from strain CNCM I 4644 is a high-efficacy, low-dose biotherapeutic candidate. This molecule offers a standardized approach to treating IBD. It may overcome the limitations and variability associated with traditional FMT.Abstract IDDF2026-ABS-0372 Figure 1Abstract IDDF2026-ABS-0372 Figure 2Abstract IDDF2026-ABS-0372 Figure 3Abstract IDDF2026-ABS-0372 Figure 4",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Yuchen Zhao"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Leiting Zhang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Xue Guo"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Youlian Zhou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Yongjian Zhou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Chen Huang"
    }
  ],
  "title": "IDDF2026-ABS-0372 Identification of a highly potent microbial anti-inflammatory molecule (MAM) from faecalibacterium prausnitzii strains",
  "uid": "7d943128-3f4a-528b-bd15-f671568a6e5e"
}