Women's Health and Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
Int J Mol Sci. 2023 Jan 5;24(2):1042. doi: 10.3390/ijms24021042.
Idiopathic granulomatous mastitis (IGM) is a rare and benign inflammatory breast disease with ambiguous aetiology. Contrastingly, lactational mastitis (LM) is commonly diagnosed in breastfeeding women. To investigate IGM aetiology, we profiled the microbial flora of pus and skin in patients with IGM and LM. A total of 26 patients with IGM and 6 patients with LM were included in the study. The 16S rRNA sequencing libraries were constructed from 16S rRNA gene amplified from total DNA extracted from pus and skin swabs in patients with IGM and LM controls. Constructed libraries were multiplexed and paired-end sequenced on HiSeq4000. Metagenomic analysis was conducted using modified microbiome abundance analysis suite customised R-resource for paired pus and skin samples. Microbiome multivariable association analyses were performed using linear models. A total of 21 IGM and 3 LM paired pus and skin samples underwent metagenomic analysis. Bray−Curtis ecological dissimilarity distance showed dissimilarity across four sample types (IGM pus, IGM skin, LM pus, and LM skin; PERMANOVA, p < 0.001). No characteristic dominant genus was observed across the IGM samples. The IGM pus samples were more diverse than corresponding IGM skin samples (Shannon and Simpson index; Wilcoxon paired signed-rank tests, p = 0.022 and p = 0.07). Corynebacterium kroppenstedtii, reportedly associated with IGM in the literature, was higher in IGM pus samples than paired skin samples (Wilcoxon, p = 0.022). Three other species and nineteen genera were statistically significant in paired IGM pus−skin comparison after antibiotic treatment adjustment and multiple comparisons correction. Microbial profiles are unique between patients with IGM and LM. Inter-patient variability and polymicrobial IGM pus samples cannot implicate specific genus or species as an infectious cause for IGM.
特发性肉芽肿性乳腺炎(IGM)是一种罕见的良性炎症性乳腺疾病,病因不明。相比之下,哺乳期乳腺炎(LM)通常发生在哺乳期妇女中。为了研究 IGM 的病因,我们对 IGM 和 LM 患者的脓液和皮肤中的微生物菌群进行了分析。本研究共纳入 26 例 IGM 患者和 6 例 LM 患者。从 IGM 和 LM 对照组患者的脓液和皮肤拭子中提取总 DNA,扩增 16S rRNA 基因,构建 16S rRNA 测序文库。构建的文库进行多重化处理,然后在 HiSeq4000 上进行 PE 测序。使用针对配对脓液和皮肤样本定制的微生物组丰度分析套件 modified microbiome abundance analysis suite 进行宏基因组分析。使用线性模型进行微生物组多变量关联分析。共对 21 例 IGM 和 3 例 LM 配对的脓液和皮肤样本进行了宏基因组分析。Bray-Curtis 生态距离显示四种样本类型(IGM 脓液、IGM 皮肤、LM 脓液和 LM 皮肤)之间存在差异(PERMANOVA,p < 0.001)。在 IGM 样本中未观察到特征性优势属。IGM 脓液样本比相应的 IGM 皮肤样本具有更高的多样性(Shannon 和 Simpson 指数;Wilcoxon 配对符号秩检验,p = 0.022 和 p = 0.07)。Corynebacterium kroppenstedtii 据报道与文献中的 IGM 有关,在 IGM 脓液样本中高于配对的皮肤样本(Wilcoxon,p = 0.022)。在抗生素治疗调整和多次比较校正后,在配对的 IGM 脓液-皮肤比较中有三个其他物种和十九个属具有统计学意义。IGM 和 LM 患者的微生物谱是独特的。个体间的变异性和多微生物 IGM 脓液样本不能暗示特定的属或种是 IGM 的感染原因。