Influence of gastrectomy for gastric cancer treatment on faecal microbiome and metabolome profiles

Erawijantari, Pande Putu
Mizutani, Sayaka
Shiroma, Hirotsugu
Shiba, Satoshi
Nakajima, Takeshi
Sakamoto, Taku
Saito, Yutaka
Fukuda, Shinji
Yachida, Shinichi
Yamada, Takuji

¹School of Life Science and Technology, Tokyo Institute of Technology, Meguro-ku, Tokyo, Japan
²Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
³Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
⁴Endoscopy Division, National Cancer Center Hospital, Tokyo, Tokyo, Japan
⁵Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
⁶Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Ebina, Kanagawa, Japan
⁷Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan
⁸Department of Cancer Genome Informatics, Graduate School of Medicine/Faculty of Medicine, Osaka University, Suita, Osaka, Japan

Correspondence to Dr Takuji Yamada, School of Life Science and Technology, Tokyo Institute of Technology, Tokyo 152-8550, Japan; [email protected]; Professor Shinichi Yachida, Department of Cancer Genome Informatics, Graduate School of Medicine/Faculty of Medicine, Osaka University, Suita, Osaka, Japan 565-0871; [email protected]

Received May 29, 2019; Revised November 26, 2019; Accepted December 02, 2019; Published Online First January 16, 2020

Twitter @erawijantaript

Contributors PPE, SM, SY and TY contributed to study concept and design. SY, SS, TN, TS and YS collected clinical samples and information. SF performed metabolome quantification. PPE, SM, HS and TY performed bioinformatics analyses on metagenomic and metabolomic data. PPE, SM, SY and TY wrote the manuscript. SY, SS and TY gave critical revision of the manuscript for important intellectual content. SY and TY supervised the study. All authors read and approved the final manuscript.

Funding This work was supported by grants from the Japan Agency for Medical Research and Development (AMED) (JP18ek0109187 to SF, SY and TY; JP19gm1010009 to SF and JP19cm0106464 to SY and TY); the National Cancer Center Research and Development Fund (25-A-4, 28-A-4, 29-A-13 and 29-A-6 to YS, SF, SY and TY); JST (Japan Science and Technology Agency)-PRESTO (JPMJPR1537 to SF and JPMJPRI507 to TY); JST-ERATO (JPMJER1902 to SF); JST-AIP Acceleration Research (JPMJCR19U3 to SY and TY); JSPS (Japan Society for the Promotion of Science) KAKENHI (142558 and 221S0002 to TY; 16H04901, 17H05654 and 18H04805 to SF); the Food Science Institute Foundation (to SF); the Program for the Advancement of Research in Core Projects under Keio University's Longevity Initiative (to SF); Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University (SY); Joint Research Project of the Institute of Medical Science, the University of Tokyo (to SY); the Takeda Science Foundation (to SY and SF); the Suzuken Memorial Foundation (to SY); the Yasuda Memorial Medical Foundation (to SY) and Yakult Bio-Science Foundation (to SY).

Competing interests SF and TY are founders of Metabologenomics. The company is focused on the design and control of the gut environment for human health. The company had no control over the interpretation, writing or publication of this work. The terms of these arrangements are being managed by Keio University and Tokyo Institute of Technology in accordance with its conflict of interest policies.

Patient consent for publication Not required.

Ethics approval The samples and clinical information used in this study were obtained under conditions of informed consent and with approval by the institutional review boards of each participating institute (National Cancer Center, 2013-244; Tokyo Institute of Technology, 2014018 and Keio University, Shonan Fujisawa Campus, 78).

Provenance and peer review Not commissioned; externally peer reviewed.

Data availability statement The raw sequencing data reported in this paper have been deposited at the DNA Data Bank of Japan (DDBJ) Sequence Read Archive (DRA), Tokyo, Japan under accession numbers DRA007281, DRA008243, DRA006684 and DRA008156. The source codes describing all of the analysis performed for this paper are available online (https://github.com/yamada-lab/GastrectomyGC_Microbiome).

Gut 69(8):p 1404-1415, August 2020. | DOI: 10.1136/gutjnl-2019-319188

ABSTRACT

Objective

Recent evidence points to the gut microbiome's involvement in postoperative outcomes, including after gastrectomy. Here, we investigated the influence of gastrectomy for gastric cancer on the gut microbiome and metabolome, and how it related to postgastrectomy conditions.

Design

We performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses on faecal samples collected from participants with a history of gastrectomy for gastric cancer (n=50) and compared them with control participants (n=56).

Results

The gut microbiota in the gastrectomy group showed higher species diversity and richness (p<0.05), together with greater abundance of aerobes, facultative anaerobes and oral microbes. Moreover, bile acids such as genotoxic deoxycholic acid and branched-chain amino acids were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p<0.05, q<0.1, LDA>2.0), as were also Kyoto Encyclopedia of Genes and Genomes modules involved in nutrient transport and organic compounds biosynthesis (LEfSe: p<0.05, q<0.1, LDA>2.0).

Conclusion

Our results reveal alterations of gut microbiota after gastrectomy, suggesting its association with postoperative comorbidities. The multi-omic approach applied in this study could complement the follow-up of patients after gastrectomy.