Lou Jiaqi, Xiang Ziyi, Zhu Xiaoyu, Li Jiliang, Jin Guoying, Cui Shengyong, Huang Neng, Xu Pei, Xu Sida, Fan Youfen, Le Xin
Burn Department, Ningbo No. 2 Hospital, No. 41 Northwest Street, Haishu District, Ningbo, 315010, Zhejiang, China.
Institute of Pathology, Faculty of Medicine, University of Bonn, 53127, Bonn, Germany.
Sci Rep. 2025 Jul 1;15(1):20656. doi: 10.1038/s41598-025-07455-y.
Hypertrophic scars (HS), classified as abnormal scarring, result from an overactive tissue response during wound healing following dermal trauma. Nonetheless, the precise mechanistic pathway underlying its occurrence remains elusive. The principal aim of this study is to elucidate the causal relationship among gut microbiota (GM), immune cell function, and hypertrophic scarring in a European demographic. Leveraging the genome-wide association analysis (GWAS) database, we conducted a two-sample Mendelian randomization (MR) study on gut microbiota (GM), immune cells, and HS. To ascertain the causality between GM, immune cells, and HS, we utilized the inverse variance weighted (IVW) method while employing multiple approaches to negate the effects of pleiotropy and heterogeneity. Furthermore, we quantitatively evaluated the influences of immune cells-mediated GM on hypertrophic scar through a two-step MR analysis. The two-sample MR analysis demonstrated a potential causality between 5 genera of gut microbiotas and 23 immune cell traits with respect to hypertrophic scarring. Further, our results showed that the causal pathway from the genus Subdoligranulum to hypertrophic scar (HS) was mediated by B cell-activating factor receptor (BAFF-R) on CD20- CD38- B cell, with a beta value of 0.034 (95% CI [0.002, 0.066]; P = 0.004), contributing to 7.60% of the total effect of Subdoligranulum on HS. Similarly, CD24 on IgD + CD38 + B cell exhibited a causal impact in the pathway from genus Coprococcus 1 to HS, with a beta value of -0.015 (95% CI [-0.029, -0.001]; P = 0.023), constituting 6.70% of the total effect of Coprococcus 1 on HS. Additionally, the CD8 + T cell %T cell mediated the causal pathway from the genus Adlercreutzia to HS with a beta value of 0.075 (95% CI [0.017, 0.133]; P = 0.024), contributing to 10.10% of the total effect of Adlercreutzia on HS. Our study indicates that the development of hypertrophic scars might be influenced by specific gut microbiota and immune cells. We highlight the possible role of two distinct immune cell genotypes as mediators in this relationship. However, most statistical significance of these findings was not maintained after FDR correction, suggesting our results should be viewed as preliminary and interpreted with caution. Further research is needed to confirm these associations.
肥厚性瘢痕（HS）被归类为异常瘢痕形成，是由真皮创伤后伤口愈合过程中过度活跃的组织反应引起的。然而，其发生背后的确切机制途径仍然难以捉摸。本研究的主要目的是阐明欧洲人群中肠道微生物群（GM）、免疫细胞功能和肥厚性瘢痕形成之间的因果关系。利用全基因组关联分析（GWAS）数据库，我们对肠道微生物群（GM）、免疫细胞和HS进行了两样本孟德尔随机化（MR）研究。为了确定GM、免疫细胞和HS之间的因果关系，我们采用逆方差加权（IVW）方法，同时采用多种方法来消除多效性和异质性的影响。此外，我们通过两步MR分析定量评估了免疫细胞介导的GM对肥厚性瘢痕的影响。两样本MR分析表明，5种肠道微生物属和23种免疫细胞特征与肥厚性瘢痕形成之间存在潜在因果关系。此外，我们的结果表明，从Subdoligranulum属到肥厚性瘢痕（HS）的因果途径是由CD20 - CD38 - B细胞上的B细胞活化因子受体（BAFF - R）介导的，β值为0.034（95%CI[0.002, 0.066]；P = 0.004），占Subdoligranulum对HS总效应的7.60%。同样，IgD + CD38 + B细胞上的CD24在从Coprococcus 1属到HS的途径中表现出因果影响，β值为 - 0.015（95%CI[-0.029, -0.001]；P = 0.023），占Coprococcus 1对HS总效应的6.70%。此外，CD8 + T细胞%T细胞介导了从Adlercreutzia属到HS的因果途径，β值为0.075（95%CI[0.017, 0.133]；P = 0.024），占Adlercreutzia对HS总效应的10.10%。我们的研究表明，肥厚性瘢痕的发展可能受到特定肠道微生物群和免疫细胞的影响。我们强调了两种不同免疫细胞基因型作为这种关系中介的可能作用。然而，在进行FDR校正后，这些发现的大多数统计学显著性并未得到维持，这表明我们的结果应被视为初步结果，并谨慎解释。需要进一步的研究来证实这些关联。
