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非哺乳期乳腺炎中乳腺组织微生物群与宿主基因调控的相互作用。

Interactions between the breast tissue microbiota and host gene regulation in nonpuerperal mastitis.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330000, Jiangxi, China.

The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, Jiangxi, China.

出版信息

Microbes Infect. 2022 Apr-May;24(3):104904. doi: 10.1016/j.micinf.2021.104904. Epub 2022 Mar 21.

DOI:10.1016/j.micinf.2021.104904
PMID:35331909
Abstract

BACKGROUND

Nonpuerperal mastitis (NPM) causes considerable psychological distress in females, since it is difficult to diagnose and treat. A spectrum of etiological factors can lead to NPM. However, the pathogenesis of NPM remains unclear. Here, we aimed to dissect the role of host gene-microbe interactions in NPM.

METHODS

We compared the breast tissue microbiome between NPM patients and controls using 16S rRNA sequencing. We also compared the gut microbiome between NPM patients and healthy controls. Moreover, we investigated whether the breast tissue microbiome was associated with an altered gut microbiome in patients with NPM. We analyzed differentially expressed genes in inflammatory tissues of mammary gland from patients with NPM and normal mammary gland tissues from patients with benign and non-infectious breast disease by RNA-sequencing (RNA-seq). Lastly, we explored the association of specific bacterial taxa with differential expression of immune-related genes and differences in infiltrating immune cells.

RESULTS

The breast tissue microbiome from NPM and controls showed significant differences in community composition. The breast tissue shared a relatively small proportion of bacterial communities with the gut in patients with NPM. Ruminococcus (family Ruminococcaceae) of breast tissue was positively correlated with the differentially expression of immune-related genes between NPM patients and controls, including antigen processing and presentation genes (ICAM1, LGMN, THBS1, TAP1, HSPA1B and HSPA1A), cytokine receptor gene IL15RA, and chemokine gene CCN1. Rhizobium of breast tissue was negatively correlated with the differentially expression of the antigen processing and presentation gene HSPA6 between NPM patients and controls. We also found that Ruminococcus (family Ruminococcaceae), Coprococcus, and Clostridium of breast tissue positively correlated with the difference of CD8 T cells between NPM patients and controls.

CONCLUSIONS

We preliminarily explored the potential role of host-microbe interactions in NPM. We demonstrate cross-talk between the breast tissue microbiome and the gut microbiome in patients with NPM. We suggest that NPM microbiome composition influences the immune microenvironment of the disease by affecting the transcriptome. This is an exploratory study and further investigation of host-microbe interactions and its potential mechanism in NPM development are warranted.

摘要

背景

非产褥期乳腺炎(NPM)会给女性带来相当大的心理困扰,因为它很难诊断和治疗。一系列病因因素可导致 NPM。然而,NPM 的发病机制尚不清楚。在这里,我们旨在剖析宿主基因-微生物相互作用在 NPM 中的作用。

方法

我们通过 16S rRNA 测序比较了 NPM 患者和对照组的乳腺组织微生物组。我们还比较了 NPM 患者和健康对照组的肠道微生物组。此外,我们研究了 NPM 患者的乳腺组织微生物组是否与肠道微生物组的改变有关。我们通过 RNA 测序(RNA-seq)分析了 NPM 患者的炎症性乳腺组织和良性及非传染性乳腺疾病患者的正常乳腺组织中差异表达的基因。最后,我们探讨了特定细菌类群与免疫相关基因差异表达和浸润免疫细胞差异的关联。

结果

NPM 患者和对照组的乳腺组织微生物组在群落组成上有显著差异。NPM 患者的乳腺组织与肠道的共享细菌群落比例相对较小。乳腺组织中的 Ruminococcus(Ruminococcaceae 科)与 NPM 患者和对照组之间免疫相关基因的差异表达呈正相关,包括抗原加工和呈递基因(ICAM1、LGMN、THBS1、TAP1、HSPA1B 和 HSPA1A)、细胞因子受体基因 IL15RA 和趋化因子基因 CCN1。乳腺组织中的 Rhizobium 与 NPM 患者和对照组之间抗原加工和呈递基因 HSPA6 的差异表达呈负相关。我们还发现,乳腺组织中的 Ruminococcus(Ruminococcaceae 科)、Coprococcus 和 Clostridium 与 NPM 患者和对照组之间 CD8 T 细胞的差异呈正相关。

结论

我们初步探讨了宿主-微生物相互作用在 NPM 中的潜在作用。我们证明了 NPM 患者的乳腺组织微生物组和肠道微生物组之间的相互作用。我们认为,NPM 微生物组组成通过影响转录组影响疾病的免疫微环境。这是一项探索性研究,需要进一步研究宿主-微生物相互作用及其在 NPM 发展中的潜在机制。

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