Journal of Microbiology and Biotechnology

  • 제34권3호
  • /
  • Pages.547-561
  • /
  • 2024
  • /
  • 1017-7825(pISSN)
  • /
  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지
DOI QR코드

DOI QR Code

Specific Alternation of Gut Microbiota and the Role of Ruminococcus gnavus in the Development of Diabetic Nephropathy

  • Jinni Hong (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Tingting Fu (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Weizhen Liu (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Yu Du (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Junmin Bu (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Guojian Wei (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Miao Yu (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Yanshan Lin (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Cunyun Min (Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University) ;
  • Datao Lin (Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University)
  • 투고 : 2023.10.20
  • 심사 : 2023.12.15
  • 발행 : 2024.03.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact of Ruminococcus gnavus (R. gnavus) on DN. Eight-week-old male KK-Ay mice were administered antibiotic cocktails for a duration of two weeks, followed by oral administration of R. gnavus for an additional eight weeks. Our study revealed significant changes in the gut microbiota during both the initiation and progression of DN. Specifically, we observed a notable increase in the abundance of Clostridia at the class level, higher levels of Lachnospirales and Oscillospirales at the order level, and a marked decrease in Clostridia_UCG-014 in DN group. Additionally, there was a significant increase in the abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Moreover, oral administration of R. gnavus effectively aggravated kidney pathology in DN mice, accompanied by elevated levels of urea nitrogen (UN), creatinine (Cr), and urine protein. Furthermore, R. gnavus administration resulted in down-regulation of tight junction proteins such as Claudin-1, Occludin, and ZO-1, as well as increased levels of uremic toxins in urine and serum samples. Additionally, our study demonstrated that orally administered R. gnavus up-regulated the expression of inflammatory factors, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) and Interleukin (IL)-6. These changes indicated the involvement of the gut-kidney axis in DN, and R. gnavus may worsen diabetic nephropathy by affecting uremic toxin levels and promoting inflammation in DN.

키워드

과제정보

The authors acknowledged Guangdong Provincial People's Hospital and Sun Yat-sen University for the academic supports.

참고문헌

  1. 2018. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392: 1736-1788.
  2. Winther SA, Henriksen P, Vogt JK, Hansen TH, Ahonen L, Suvitaival T, et al. 2020. Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria. Diabetologia 63: 2713-2724.
  3. Jin Q, Ma R. 2021. Metabolomics in diabetes and diabetic complications: insights from epidemiological studies. Cells 10: 2832.
  4. Meijers B, Evenepoel P, Anders HJ. 2019. Intestinal microbiome and fitness in kidney disease. Nat. Rev. Nephrol. 15: 531-545.
  5. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482: 179-185.
  6. Adeshirlarijaney A, Zou J, Tran HQ, Chassaing B, Gewirtz AT. 2019. Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota. Am. J. Physiol. Endocrinol. Metab. 317: E1121-E1130.
  7. Meijnikman AS, Gerdes VE, Nieuwdorp M, Herrema H. 2018. Evaluating causality of gut microbiota in obesity and diabetes in humans. Endocr. Rev. 39: 133-153.
  8. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. 2012. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490: 55-60.
  9. Salguero MV, Al-Obaide MAI, Singh R, Siepmann T, Vasylyeva TL. 2019. Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp. Ther. Med. 18: 3461-3469.
  10. Anders HJ, Andersen K, Stecher B. 2013. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 83: 1010-1016.
  11. Yang G, Wei J, Liu P, Zhang Q, Tian Y, Hou G, et al. 2021. Role of the gut microbiota in type 2 diabetes and related diseases. Metabolism117: 154712.
  12. Cai TT, Ye XL, Li RR, Chen H, Wang YY, Yong HJ, et al. 2020. Resveratrol modulates the gut microbiota and inflammation to protect against diabetic nephropathy in mice. Front. Pharmacol.11: 1249.
  13. Ramezani A, Raj DS. 2014. The gut microbiome, kidney disease, and targeted interventions. J. Am. Soc. Nephrol. 25: 657-670.
  14. Tang WHW, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. 2015. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ. Res. 116: 448-455.
  15. Sivaprakasam S, Prasad PD, Singh N. 2016. Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis. Pharmacol. Ther. 164: 144-151.
  16. Hernandez MAG, Canfora EE, Jocken JWE, Blaak EE. 2019. The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients 11: 1943.
  17. Crost EH, Coletto E, Bell A, Juge N. 2023. Ruminococcus gnavus: friend or foe for human health. FEMS Microbiol. Rev. 47: fuad014.
  18. Grahnemo L, Nethander M, Coward E, Gabrielsen ME, Sree S, Billod JM, et al. 2022. Cross-sectional associations between the gut microbe Ruminococcus gnavus and features of the metabolic syndrome. Lancet Diabetes Endocrinol. 10: 481-483.
  19. Lee MJ, Kang MJ, Lee SY, Lee E, Kim K, Won S, et al. 2018. Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type. J Allergy Clin. Immunol. 141: 1310-1319.
  20. Sokol H, Jegou S, McQuitty C, Straub M, Leducq V, Landman C, et al. 2018. Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection. Gut Microbes 9: 55-60.
  21. Jung CY, Yoo TH. 2022. Pathophysiologic mechanisms and potential biomarkers in diabetic kidney disease. Diabetes Metab. J. 46: 181-197.
  22. Hotamisligil GS. 2006. Inflammation and metabolic disorders. Nature 444: 860-867.
  23. Nicholas SB. 2021. Novel anti-inflammatory and anti-fibrotic agents for diabetic kidney disease-from bench to bedside. Adv. Chronic Kidney Dis. 28: 378-390.
  24. Hong J, Li G, Zhang Q, Ritter J, Li W, Li PL. 2019. D-Ribose induces podocyte NLRP3 inflammasome activation and glomerular injury via AGEs/RAGE pathway. Front. Cell. Dev. Biol. 7: 259.
  25. Fan Q, Shike T, Shigihara T, Tanimoto M, Gohda T, Makita Y, et al. 2003. Gene expression profile in diabetic KK/Ta mice. Kidney Int. 64: 1978-1985.
  26. Okazaki M, Saito Y, Udaka Y, Maruyama M, Murakami H, Ota S, et al. 2002. Diabetic nephropathy in KK and KK-Ay mice. Exp. Anim. 51: 191-196.
  27. Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J. 2019. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc. Natl. Acad. Sci. USA 116: 12672-12677.
  28. Ahn JR, Lee SH, Kim B, Nam MH, Ahn YK, Park YM, et al. 2022. Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice. Pediatr. Allergy Immunol. 33: e13678.
  29. Liu C, Zhao D, Ma W, Guo Y, Wang A, Wang Q, et al. 2016. Denitrifying sulfide removal process on high-salinity wastewaters in the presence of Halomonas sp. Appl. Microbiol. Biotechnol. 100: 1421-1426.
  30. Chen S, Zhou Y, Chen Y, Gu J. 2018. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34: i884-i890.
  31. Magoc T, Salzberg SL. 2011. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27: 2957-2963.
  32. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. 2016. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13: 581-583.
  33. Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, Alexander H , et al. 2019. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37: 852-857.
  34. Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, et al. 2009. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75: 7537-7541.
  35. Randall DW, Kieswich J, Hoyles L, McCafferty K, Curtis M, Yaqoob MM. 2023. Gut dysbiosis in experimental kidney disease: a meta-analysis of rodent repository data. J. Am. Soc. Nephrol. 34: 533-553.
  36. Iddings AC, Shenoi AN, Pozzo AM, Kiessling SG. 2017. Hemolytic uremic syndrome complicated by Clostridium septicum bacteremia and new-onset type 1 diabetes mellitus. report of a case. Clin. Nephrol. 87: 207-211.
  37. Mirzai S, Rifai AO, Webb S, Rifai K, Reiner A. 2019. Probable Clostridium septicum pneumocephalus in a user of natural remedies with newly diagnosed diabetes mellitus type 1. IDCases 17: e581.
  38. Goldberg E, Krause I. 2009. Infection and type 1 diabetes mellitus - a two edged sword?. Autoimmun. Rev. 8: 682-686.
  39. de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, Harkonen T, Orivuori L, et al. 2013. Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes 62: 1238-1244.
  40. Jamshidi P, Hasanzadeh S, Tahvildari A, Farsi Y, Arbabi M, Mota JF, et al. 2019. Is there any association between gut microbiota and type 1 diabetes? A systematic review. Gut Pathog. 11: 49.
  41. Zhao M, Xu S, Cavagnaro MJ, Zhang W, Shi J. 2021. Quantitative analysis and visualization of the interaction between intestinal microbiota and type 1 diabetes in children based on multi-databases. Front. Pediatr. 9: 752250.
  42. Cinek O, Kramna L, Mazankova K, Odeh R, Alassaf A, Ibekwe MAU, et al. 2018. The bacteriome at the onset of type 1 diabetes: a study from four geographically distant African and Asian countries. Diabetes Res. Clin. Pract. 144: 51-62.
  43. Vatanen T, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, et al. 2018. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562: 589-594.
  44. Endesfelder D, Engel M, Davis-Richardson AG, Ardissone AN, Achenbach P, Hummel S, et al. 2016. Towards a functional hypothesis relating anti-islet cell autoimmunity to the dietary impact on microbial communities and butyrate production. Microbiome 4: 17.
  45. Wang X, Liu H, Li Y, Huang S, Zhang L, Cao C, et al. 2020. Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus. Gut Microbes 12: 1-13.
  46. Wang Y, Zhao J, Qin Y, Yu Z, Zhang Y, Ning X, et al. 2022. The specific alteration of gut microbiota in diabetic kidney diseases-A systematic review and meta-analysis. Front. Immunol. 13: 908219.
  47. Mokkala K, Houttu N, Vahlberg T, Munukka E, Ronnemaa T, Laitinen K. 2017. Gut microbiota aberrations precede diagnosis of gestational diabetes mellitus. Acta Diabetol. 54: 1147-1149.
  48. Zhao JD, Li Y, Sun M, Yu CJ, Li JY, Wang SH, et al. 2021. Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats. World J. Gastroenterol. 27: 708-724.
  49. Liu C, Finegold SM, Song Y, Lawson PA. 2008. Reclassification of Clostridium coccoides, Ruminococcus hansenii, Ruminococcus hydrogenotrophicus, Ruminococcus luti, Ruminococcus productus and Ruminococcus schinkii as Blautia coccoides gen. nov., comb. nov., Blautia hansenii comb. nov., Blautia hydrogenotrophica comb. nov., Blautia luti comb. nov., Blautia producta comb. nov., Blautia schinkii comb. nov. and description of Blautia wexlerae sp. nov., isolated from human faeces. Int. J. Syst. Evol. Microbiol. 58: 1896-1902.
  50. Evenepoel P, Poesen R, Meijers B. 2017. The gut-kidney axis. Pediatr. Nephrol. 32: 2005-2014.
  51. Su X, Yu W, Liu A, Wang C, Li X, Gao J, et al. 2021. San-Huang-Yi-Shen capsule ameliorates diabetic nephropathy in rats through modulating the gut microbiota and overall metabolism. Front. Pharmacol. 12: 808867.