{
  "abstract": "Background Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation, mucosal barrier disruption, and dysregulated immune responses. Gut microbial extracellular vesicles (EVs) have emerged as important mediators of host–microbe communication and may provide a safer alternative to live bacterial therapy. Parabacteroides distasonis is a core commensal bacterium with potential anti-inflammatory activity, but whether its derived EVs ameliorate colitis and the underlying mechanisms remain unclear. This study aimed to investigate the protective effects of P. distasonis-derived EVs (P.d EVs) on experimental colitis, their role in regulating CD4+ T-cell-mediated immune responses, and the potential contribution of GroEL.Methods P.d EVs were isolated and characterized by transmission electron microscopy, NanoFCM, and zeta potential analysis. Acute colitis was induced in C57BL/6 mice using dextran sulfate sodium (DSS), followed by oral administration of P.d EVs. Disease severity was evaluated by body weight loss, disease activity index, colon length, and histopathological scoring. Mucosal barrier integrity was assessed by PAS and Alcian blue staining, immunohistochemical analysis of barrier-related proteins, and intestinal permeability assays. Flow cytometry was performed to analyze immune cell populations in the colonic lamina propria, with focus on CD4+ T-cell subsets. Anti-CD4 antibody treatment was used to assess changes in the protective effects of P.d EVs under CD4+ T-cell-depleted conditions. Purified GroEL protein was used for in vivo functional validation.Results P.d EVs alleviated DSS-induced colitis, as shown by reduced weight loss, lower disease activity scores, preserved colon length, and improved histological injury. P.d EVs also promoted mucosal barrier repair by restoring goblet cell-associated mucus production, increasing barrier-related protein expression, and reducing intestinal permeability (IDDF2026-ABS-0529 Figure 1). Immune profiling showed that P.d EVs reshaped the colonic immune microenvironment and were associated with altered CD4+ T-cell differentiation, particularly a rebalanced Th17/Treg response (IDDF2026-ABS-0529 Figure 2). Under anti-CD4 antibody treatment, the protective effects of P.d EVs were attenuated (IDDF2026-ABS-0529 Figure 3). Purified GroEL partially reproduced the protective effects of P.d EVs on colitis, mucosal barrier function, and colonic CD4+ T-cell responses (IDDF2026-ABS-0529 Figure 4).Conclusions P.d EVs ameliorate experimental colitis and promote mucosal barrier repair, at least in part through modulation of CD4+ T-cell-mediated immune responses. GroEL may represent a functional mediator contributing to the protective and immunoregulatory effects of P.d EVs.Abstract IDDF2026-ABS-0529 Figure 1Abstract IDDF2026-ABS-0529 Figure 2Abstract IDDF2026-ABS-0529 Figure 3Abstract IDDF2026-ABS-0529 Figure 4",
  "authors": [
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Ping Gao"
    },
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Zibo Zhang"
    },
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Bing Wang"
    },
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Zeyang Fu Junyan He"
    },
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Yanchen Li"
    },
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Yahui Guo"
    },
    {
      "affiliations": [
        "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Xiaolan Zhang"
    }
  ],
  "title": "IDDF2026-ABS-0529 Parabacteroides distasonis-derived extracellular vesicles alleviate colitis through modulation of CD4+ T-cell responses",
  "uid": "323b916b-82b6-56e5-9d3a-36fb0ff73f18"
}