Sphingomonas and Phenylobacterium as Major Microbiota in Thymic Epithelial Tumors.

Rumi Higuchi,Kenji Amemiya,Hiroshi Ohyama,Masao Omata,Yosuke Hirotsu,Sotaro Otake,Toshio Oyama,Hitoshi Mochizuki,Taichiro Goto

doi:10.3390/jpm11111092

Abstract

Simple SummaryIn this study, we evaluated the microbiota in resected thymoma samples and identified Sphingomonas and Phenylobacterium as the dominant genera in thymomas. This is the first study that evaluated the microbiota in thymoma and that identified bacterial genera specific to thymoma. Furthermore, our study indicates a potential approach for preventing the development of thymoma as a new “precision medicine”.The microbiota has been reported to be closely associated with carcinogenesis and cancer progression. However, its involvement in the pathology of thymoma remains unknown. In this study, we aimed to identify thymoma-specific microbiota using resected thymoma samples. Nineteen thymoma tissue samples were analyzed through polymerase chain reaction amplification and 16S rRNA gene sequencing. The subjects were grouped according to histology, driver mutation status in the GTF2I gene, PD-L1 status, and smoking habits. To identify the taxa composition of each sample, the operational taxonomic units (OTUs) were classified on the effective tags with 97% identity. The Shannon Index of the 97% identity OTUs was calculated to evaluate the alpha diversity. The linear discriminant analysis effect size (LEfSe) method was used to compare the relative abundances of all the bacterial taxa. We identified 107 OTUs in the tumor tissues, which were classified into 26 genera. Sphingomonas and Phenylobacterium were identified as abundant genera in almost all the samples. No significant difference was determined in the alpha diversity within these groups; however, type A thymoma tended to exhibit a higher bacterial diversity than type B thymoma. Through the LEfSe analysis, we identified the following differentially abundant taxa: Bacilli, Firmicutes, and Lactobacillales in type A thymoma; Proteobacteria in type B thymoma; Gammaproteobacteria in tumors harboring the GTF2I mutation; and Alphaproteobacteria in tumors without the GTF2I mutation. In conclusion, Sphingomonas and Phenylobacterium were identified as dominant genera in thymic epithelial tumors. These genera appear to comprise the thymoma-specific microbiota.

Highlights

Microbiome research focused primarily on gastrointestinal diseases, such as pseudomembranous enterocolitis, inflammatory bowel disease, and irritable colitis [1]
On the basis of the results from these analyses, we presented a predictive model of pathogenesis and evaluated its potential for the prevention and control of the development of thymoma
Nineteen consecutive patients with thymomas who underwent surgery at our hospital between January 2014 and August 2020 were enrolled without bias

Summary

Introduction

Microbiome research focused primarily on gastrointestinal diseases, such as pseudomembranous enterocolitis, inflammatory bowel disease, and irritable colitis [1]. The human intestinal microbiota has been reported to be involved in carcinogenesis and cancer progression, and this phenomenon has been attracting attention [2,3]. Thymoma is a relatively rare mediastinal tumor with malignant potential that is difficult to treat [9,10]. According to the histological classification by the World Health Organization, thymomas can be categorized into types A, AB, B1, B2, and B3, depending on the tumor cell morphology and proportion of coexisting lymphocytes [11]. Thymoma has been reported to commonly occur in people aged 40–60 years [14]. Thymoma coexists in approximately 20% of patients with myasthenia gravis [16,17]. Owing to the absence of an effective treatment other than surgical resection, there is an urgent need to elucidate the pathology and establish preventive measures and new treatment strategies for thymoma [18,19,20,21]

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