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Duodenal microbiome in chronic kidney disease

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Abstract

Background

The intestinal microbiome is involved in the pathogenesis of chronic kidney disease (CKD). Despite its importance, the microbiome of the small intestinal mucosa has been little studied due to sampling difficulties, and previous studies have mainly focused on fecal sources for microbiome studies. We aimed to characterize the small intestinal microbiome of CKD patients by studying the microbiome collected from duodenal and fecal samples of CKD patients and healthy controls.

Methods

Overall, 28 stage 5 CKD patients and 21 healthy participants were enrolled. Mucosal samples were collected from the deep duodenum during esophagogastroduodenoscopy and fecal samples were also collected. The 16S ribosomal RNA gene sequencing using Qiime2 was used to investigate and compare the microbial structure and metagenomic function of the duodenal and fecal microbiomes.

Results

The duodenal flora of CKD patients had decreased alpha diversity compared with the control group. On the basis of taxonomic composition, Veillonella and Prevotella were significantly reduced in the duodenal flora of CKD patients. The tyrosine and tryptophan metabolic pathways were enhanced in the urea toxin-related metabolic pathways based on the Kyoto Encyclopedia of Genes and Genomes database.

Conclusion

The small intestinal microbiome in CKD patients is significantly altered, indicating that increased intestinal permeability and production of uremic toxin may occur in the upper small intestine of CKD patients.

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References

  1. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–72.

    Article  PubMed  Google Scholar 

  2. Agus A, Planchais J, Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018;23:716–24.

    Article  CAS  PubMed  Google Scholar 

  3. Mishima E, Fukuda S, Mukawa C, et al. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach. Kidney Int. 2017;92:634–45.

    Article  CAS  PubMed  Google Scholar 

  4. Koeth RA, WangLevison ZB, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Vaziri ND, Yuan J, Rahimi A, Ni Z, Said H, Subramanian VS. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012;27:2686–93.

    Article  CAS  PubMed  Google Scholar 

  6. Sun CY, Chang SC, Wu MS. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS ONE. 2012;7:e34026.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vanholder R, Schepers E, Pletinck A, Nagler EV, Glorieux G. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J Am Soc Nephrol. 2014;25:1897–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sabatino A, Regolisti G, Brusasco I, Cabassi A, Morabito S, Fiaccadori E. Alterations of intestinal barrier and microbiota in chronic kidney disease. Nephrol Dial Transplant. 2015;30:924–33.

    Article  CAS  PubMed  Google Scholar 

  9. Darisipudi MN, Knauf F. An update on the role of the inflammasomes in the pathogenesis of kidney diseases. Pediatr Nephrol. 2016;31:535–44.

    Article  PubMed  Google Scholar 

  10. Meijers BK. Evenepoel P The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant. 2011;26:759–61.

    Article  CAS  PubMed  Google Scholar 

  11. Nagasue T, Hirano A, Torisu T, et al. The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted. Enteroscopy Digest. 2022;103:308–18.

    Article  CAS  Google Scholar 

  12. Leite GGS, Weitsman S, Parodi G, et al. Mapping the Segmental Microbiomes in the Human Small Bowel in Comparison with Stool: A REIMAGINE Study. Dig Dis Sci. 2020;65:2595–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Stremmel W, Schmidt KV, Schuhmann V, et al. Blood Trimethylamine-N-Oxide Originates from Microbiota Mediated Breakdown of Phosphatidylcholine and Absorption from Small Intestine. PLoS ONE. 2017;12: e0170742.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Meier KHU, Trouillon J, Li Het al. . Metabolic landscape of the male mouse gut identifies different niches determined by microbial activities Nat Metab. 2023.

  15. Hirano A, Umeno J, Okamoto Yet al. Comparison of the microbial community structure between inflamed and non-inflamed sites in patients with ulcerative colitis J Gastroenterol Hepatol. 2018.

  16. Bolyen E, Rideout JR, Dillon MRet al. . Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2 Nat Biotechnol. 2019;37:852–857.

  17. Quast C, Pruesse E, Yilmaz P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41:D590-596.

    Article  CAS  PubMed  Google Scholar 

  18. Douglas GM, Maffei VJ, Zaneveld JR, et al. PICRUSt2 for prediction of metagenome functions. Nat Biotechnol. 2020;38:685–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Caspi R, Billington R, Keseler IMet al. The MetaCyc database of metabolic pathways and enzymes - a 2019 update Nucleic Acids Res. 2020;48:D445-d453.

  20. Parks DH, Tyson GW, Hugenholtz P, Beiko RG. STAMP: statistical analysis of taxonomic and functional profiles Bioinformatics. 2014;30:3123–3124.

  21. Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM. Chronic kidney disease and the gut microbiome. Am J Physiol Renal Physiol. 2019;316:F1211-f1217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li F, Wang M, Wang J, Li R, Zhang Y. Alterations to the gut microbiota and their correlation with inflammatory factors in chronic kidney disease. Front Cell Infect Microbiol. 2019;9:206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wu IW, Gao SS, Chou HC, et al. Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease. Theranostics. 2020;10:5398–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015;33:496–503.

    Article  CAS  PubMed  Google Scholar 

  25. Hu J, Iragavarapu S, Nadkarni GN, et al. Location-Specific Oral Microbiome Possesses Features Associated With CKD Kidney. Int Rep. 2018;3:193–204.

    Google Scholar 

  26. Kim JE, Kim HE, Park JIet al. . The Association between Gut Microbiota and Uremia of Chronic Kidney Disease Microorganisms. 2020;8.

  27. Jiang S, Xie S, Lv D, et al. Alteration of the gut microbiota in Chinese population with chronic kidney disease. Sci Rep. 2017;7:2870.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  28. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–50.

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Devlin AS, Marcobal A, Dodd D, et al. Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota. Cell Host Microbe. 2016;20:709–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Di Iorio BR, Rocchetti MT, De Angelis Met al. . Nutritional Therapy Modulates Intestinal Microbiota and Reduces Serum Levels of Total and Free Indoxyl Sulfate and P-Cresyl Sulfate in Chronic Kidney Disease (Medika Study) J Clin Med. 2019;8.

  31. Wheeler R, Bastos PAD, Disson O, et al. Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination. Proc Natl Acad Sci USA. 2023;120: e2209936120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Asao T, Oki K, Yoneda M, Tanaka J, Kohno N. Hypothalamic-pituitary-adrenal axis activity is associated with the prevalence of chronic kidney disease in diabetic patients. Endocr J. 2016;63:119–26.

    Article  CAS  PubMed  Google Scholar 

  33. Banoglu E, Jha GG, King RS. Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur J Drug Metab Pharmacokinet. 2001;26:235–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang X, Yang S, Li S, et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. Gut. 2020;69:2131–42.

    Article  CAS  PubMed  Google Scholar 

  35. Thaiss CA, Zeevi D, Levy M, et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014;159:514–29.

    Article  CAS  PubMed  Google Scholar 

  36. Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota. Science. 2013;341:1237439.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Nagata N, Nishijima S, Miyoshi-Akiyama T, et al. Population-level metagenomics uncovers distinct effects of multiple medications on the human gut microbiome. Gastroenterology. 2022;163:1038–52.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Wendy Hempstock, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study was supported by JSPS KAKENHI Grant Number JP21K06783, Grant-in-Aid for Scientific Research C.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maida-Shi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan

    Masahiro Kondo, Takehiro Torisu, Tomohiro Nagasue, Junji Umeno, Keisuke Kawasaki, Shin Fujioka, Yuichi Matsuno, Tomohiko Moriyama & Takanari Kitazono

  2. Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Hiroki Shibata

  3. International Medical Department, Kyushu University Hospital, Fukuoka, Japan

    Tomohiko Moriyama

Authors
  1. Masahiro Kondo
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  2. Takehiro Torisu
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  3. Tomohiro Nagasue
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  4. Hiroki Shibata
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  5. Junji Umeno
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  6. Keisuke Kawasaki
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  7. Shin Fujioka
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  8. Yuichi Matsuno
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  10. Takanari Kitazono
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Contributions

Conceptualization: MK, TT, TN, JU, KK, SF, YM, and TM contributed to the conception and design of this study. MK, TN, TT, and TK proofread this manuscript. H.S. was central to the acquisition of the sequence data. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Takehiro Torisu.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of the Kyushu University Medical School District Office (Permit No. 2020-332).

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Kondo, M., Torisu, T., Nagasue, T. et al. Duodenal microbiome in chronic kidney disease. Clin Exp Nephrol 28, 263–272 (2024). https://doi.org/10.1007/s10157-023-02434-x

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