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Theranostics 2020; 10(12):5398-5411. doi:10.7150/thno.41725 This issue Cite

Research Paper

Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease

I-Wen Wu1,2, Sheng-Siang Gao3, Hsin-Cheng Chou3, Huang-Yu Yang2,4,5, Lun-Ching Chang6, Yu-Lun Kuo7, Michael Cong Vinh Dinh8, Wen-Hung Chung9, Chi-Wei Yang2,4, Hsin-Chih Lai10,11,12, Wen-Ping Hsieh3, Shih-Chi Su9✉

1. Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan
2. College of Medicine, Chang Gung University, Taoyuan, Taiwan
3. Institute of Statistics, National Tsing-Hua University, Hsinchu, Taiwan
4. Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkuo, Taiwan
5. Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, US
6. Department of Mathematical Sciences, Florida Atlantic University, Florida, US
7. Biotools, Co., Ltd, New Taipei City, Taiwan
8. Department of Computer Science, Florida Atlantic University, Florida, US
9. Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan
10. Department of Medical Biotechnology and Laboratory Science, and Microbiota Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
11. Central Research Laboratory, XiaMen Chang Gung Hospital, XiaMen, China
12. Department of Laboratory Medicine, Chang Gung Memorial hospital, Linkuo, Taiwan

✉ Corresponding author: Shih-Chi Su, PhD. Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan. 222, Mai-Chin Road, Keelung 20401, Taiwan; Phone: 886-2-24329292-3388; Fax: +886-2-27191623; Email: ssu1org.tw More

Citation:
Wu IW, Gao SS, Chou HC, Yang HY, Chang LC, Kuo YL, Dinh MCV, Chung WH, Yang CW, Lai HC, Hsieh WP, Su SC. Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease. Theranostics 2020; 10(12):5398-5411. doi:10.7150/thno.41725. https://www.thno.org/v10p5398.htm
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Abstract

Graphic abstract

Chronic kidney disease (CKD) is a serious healthcare dilemma, associated with specific changes in gut microbiota and circulating metabolome. Yet, the functional capacity of CKD microbiome and its intricate relationship with the host metabolism at different stages of disease are less understood. Methods: Here, shotgun sequencing of fecal samples and targeted metabolomics profiling of serum bile acids, short- and medium-chain fatty acids, and uremic solutes were performed in a cohort of CKD patients with different severities and non-CKD controls. Results: We identified that levels of 13 microbial species and 6 circulating metabolites were significantly altered across early to advanced stages or only in particular stage(s). Among these, Prevotella sp. 885 (decreased) was associated with urea excretion, while caproic acid (decreased) and p-cresyl sulfate (elevated) were positively and negatively correlated with the glomerular filtration rate, respectively. In addition, we identified gut microbial species linked to changes in circulating metabolites. Microbial genes related to secondary bile acid biosynthesis were differentially abundant at the early stage, while pathway modules related to lipid metabolism and lipopolysaccharide biosynthesis were enriched in the CKD microbiome at the advanced stage, suggesting that changes in microbial metabolism and host inflammation may contribute to renal health. Further, we identified metagenomic and metabolomic markers to discriminate cases of different severities from the controls, among which Bacteroides eggerthii individually was of particular value in early diagnosis. Conclusions: Our dual-omics data reveal the connections between intestinal microbes and circulating metabolites perturbed in CKD, which may be of etiological and diagnostic importance.

Keywords: Chronic kidney disease, Gut microbiome, Serum metabolites, Short-chain fatty acid, Uremic solute

Citation styles

APA
Wu, I.W., Gao, S.S., Chou, H.C., Yang, H.Y., Chang, L.C., Kuo, Y.L., Dinh, M.C.V., Chung, W.H., Yang, C.W., Lai, H.C., Hsieh, W.P., Su, S.C. (2020). Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease. Theranostics, 10(12), 5398-5411. https://doi.org/10.7150/thno.41725.

ACS
Wu, I.W.; Gao, S.S.; Chou, H.C.; Yang, H.Y.; Chang, L.C.; Kuo, Y.L.; Dinh, M.C.V.; Chung, W.H.; Yang, C.W.; Lai, H.C.; Hsieh, W.P.; Su, S.C. Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease. Theranostics 2020, 10 (12), 5398-5411. DOI: 10.7150/thno.41725.

NLM
Wu IW, Gao SS, Chou HC, Yang HY, Chang LC, Kuo YL, Dinh MCV, Chung WH, Yang CW, Lai HC, Hsieh WP, Su SC. Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease. Theranostics 2020; 10(12):5398-5411. doi:10.7150/thno.41725. https://www.thno.org/v10p5398.htm

CSE
Wu IW, Gao SS, Chou HC, Yang HY, Chang LC, Kuo YL, Dinh MCV, Chung WH, Yang CW, Lai HC, Hsieh WP, Su SC. 2020. Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease. Theranostics. 10(12):5398-5411.

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