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

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.

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.

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.

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.