In-Depth Metaproteomics Analysis of Oral Microbiome for Lung Cancer

Author:

Jiang Xiaoteng1,Zhang Yan2,Wang Huiyu1,Wang Zeyuan1,Hu Shen3ORCID,Cao Chengxi4ORCID,Xiao Hua1ORCID

Affiliation:

1. State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China

2. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

3. School of Dentistry and Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles 90095, USA

4. Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

Abstract

The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced Fusobacterium nucleatum and Prevotella histicola and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.

Funder

Key Scientific Project of Shanghai Jiao Tong University

National Natural Science Foundation of China

National Basic Research Program of China

Natural Science Foundation of Shanghai

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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