肠道微生物网络在高草酸诱导大鼠肾损伤中的保护作用

doi:10.3969/j.issn.1006-5725.2024.13.002

Abstract

Abstract:

Objective To explore the effects of fecal microbiota transplantation （FMT） on oxalate metabolism and renal protection in rats fed a high oxalate diet. Methods Twenty-four male SD rats were randomly divided into four groups： SC， SC + FMT， OD + PBS and OD + FMT. The SC group was set as the control group and was fed standard rat chow. The OD + PBS group and OD + FMT group were fed a diet containing 5% oxalate. Starting from day 14， the OD + PBS group， OD + FMT group and SC + FMT group received intragastric administration of PBS solution or filtered faecal microbiota solution from guinea pigs for 7 consecutive days. The 24-hour urine， feces， and venous serum of the rats were collected from the rats of all groups to determine the gut microbiota and biochemical markers. Real-time quantitative PCR and immunohistochemistry were conducted on the rat kidneys to detect the expression of renin， ACE， and OPN. Results The fecal microbiota transplantation altered the gut microbiota of rats. The gut microbiota of the SC + FMT group deviated from that of the SC group and showed increased similarity to that of the guinea pigs. Compared to the OD + PBS group， the OD + FMT group exhibited significant reductions in the urinary oxalate， urinary urea， uric acid， urinary creatinine， serum urea nitrogen/creatinine， and serum uric acid. Furthermore， after FMT treatment， the OD + FMT group exhibited reduced upregulation of renin mRNA expression and restored downregulation of OPN mRNA expression compared to the OD + PBS group； similar results were obtained from immunohistochemistry. Conclusion Fecal microbiome trans-plantation activated the microbial network in the rat gut， particularly the oxalate-degrading bacteria represented by Muribaculaceae. The kidney injury induced by high oxalate was partially restored by the microbiota network's degradation of oxalate， indicating the protective effect of fecal microbiota transplantation on the rat kidneys.

Key words: fecal microbiota transplantation, microbial network, calcium oxalate stone, renal protection

CLC Number:

R446.139

Yan WANG,Tiejun PAN,Zhenyu LIU,Jinbo SUN,Yu ZHOU,Chaosheng LI,Lei. GAO. Protective role of intestinal microbial network in hyperoxaluria⁃induced kidney impairment in rats[J]. The Journal of Practical Medicine, 2024, 40(13): 1771-1777.

Figures/Tables 6

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References 27

1	吴志良. 不同手术方式治疗男性复杂性肾结石的疗效和对患者性功能影响的比较［J］. 实用医学杂志， 2018，34（20）：3449-3453. doi:10.3969/j.issn.1006-5725.2018.20.030 doi: 10.3969/j.issn.1006-5725.2018.20.030
2	XU L， ADAMS-HUET B， POINDEXTER J R， et al. Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation［J］. J Urol， 2017，197（6）：1465-1471. doi:10.1016/j.juro.2017.01.057 doi: 10.1016/j.juro.2017.01.057
3	LIESKE J C， PEÑA DE LA VEGA L S， SLEZAK J M， et al. Renal stone epidemiology in Rochester， Minnesota： An update［J］. Kidney Int， 2006，69（4）：760-764. doi:10.1038/sj.ki.5000150 doi: 10.1038/sj.ki.5000150
4	CIL O， CHU T， LEE S， et al. Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis［J］. JCI Insight， 2022，7（13）：e153359. doi:10.1172/jci.insight.153359 doi: 10.1172/jci.insight.153359
5	CANALES B K， HATCH M. Kidney stone incidence and metabolic urinary changes after modern bariatric surgery： review of clinical studies， experimental models， and prevention strategies［J］. Surg Obes Relat Dis， 2014，10（4）：734-742. doi:10.1016/j.soard.2014.03.026 doi: 10.1016/j.soard.2014.03.026
6	HOLMES R P， KNIGHT J， ASSIMOS D G. Lowering urinary oxalate excretion to decrease calcium oxalate stone disease［J］. Urolithiasis， 2016，44（1）：27-32. doi:10.1007/s00240-015-0839-4 doi: 10.1007/s00240-015-0839-4
7	MITCHELL T， KUMAR P， REDDY T， et al. Dietary oxalate and kidney stone formation［J］. Am J Physiol Renal Physiol， 2019，316（3）： F409-F413. doi:10.1152/ajprenal.00373.2018 doi: 10.1152/ajprenal.00373.2018
8	TURRONI S， BENDAZZOLI C， DIPALO S C F， et al. Oxalate-Degrading Activity inBifidobacterium animalis subsp.lactis： Impact of Acidic Conditions on the Transcriptional Levels of the Oxalyl Coenzyme A （CoA） Decarboxylase and Formyl-CoA Transferase Genes［J］. Appl Environ Microbiol， 2010，76（16）：5609-5620. doi:10.1128/aem.00844-10 doi: 10.1128/aem.00844-10
9	MOGNA L， PANE M， NICOLA S， et al. Screening of Different Probiotic Strains for Their In Vitro Ability to Metabolise Oxalates： Any Prospective Use in Humans？［J］. J Clin Gastroenterol， 2014，48（Supp1）：S91-S95. doi:10.1097/mcg.0000000000000228 doi: 10.1097/mcg.0000000000000228
10	KAUFMAN D W， KELLY J P， CURHAN G C， et al. Oxalobacter formigenes May Reduce the Risk of Calcium Oxalate Kidney Stones［J］. J Am Soc Nephrol， 2008，19（6）：1197-1203. doi:10.1681/asn.2007101058 doi: 10.1681/asn.2007101058
11	STERN J M， MOAZAMI S， QIU Y， et al. Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers［J］. Urolithiasis， 2016，44（5）：399-407. doi:10.1007/s00240-016-0882-9 doi: 10.1007/s00240-016-0882-9
12	TICINESI A， MILANI C， GUERRA A， et al. Understanding the gut–kidney axis in nephrolithiasis： an analysis of the gut microbiota composition and functionality of stone formers［J］. Gut， 2018，67（12）：2097-2106. doi:10.1136/gutjnl-2017-315734 doi: 10.1136/gutjnl-2017-315734
13	TAVASOLI S， ALEBOUYEH M， NAJI M， et al. Association of intestinal oxalate‐degrading bacteria with recurrent calcium kidney stone formation and hyperoxaluria： a case–control study［J］. BJU Int， 2020，125（1）：133-143. doi:10.1111/bju.14840 doi: 10.1111/bju.14840
14	CHEN F， BAO X， LIU S， et al. Gut microbiota affect the formation of calcium oxalate renal calculi caused by high daily tea consumption［J］. Appl Microbiol Biotechnol， 2021，105（2）：789-802. doi:10.1007/s00253-020-11086-w doi: 10.1007/s00253-020-11086-w
15	GOLDFARB D S， MODERSITZKI F， ASPLIN J R. A Randomized， Controlled Trial of Lactic Acid Bacteria for Idiopathic Hyperoxaluria［J］. Clin J Am Soc Nephrol， 2007，2（4）：745-749. doi:10.2215/cjn.00600207 doi: 10.2215/cjn.00600207
16	HOPPE B， GROOTHOFF J W， HULTON S， et al. Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria［J］. Nephrol Dial Transplant， 2011，26（11）：3609-3615. doi:10.1093/ndt/gfr107 doi: 10.1093/ndt/gfr107
17	SIENER R， BADE D J， HESSE A， et al. Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria［J］. J Transl Med， 2013，11：306. doi:10.1186/1479-5876-11-306 doi: 10.1186/1479-5876-11-306
18	HOPPE B， NIAUDET P， SALOMON R， et al. A randomised Phase I/II trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria［J］. Pediatr Nephrol， 2017，32（5）：781-790. doi:10.1007/s00467-016-3553-8 doi: 10.1007/s00467-016-3553-8
19	MILLINER D， HOPPE B， GROOTHOFF J. A randomised Phase II/III study to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria［J］.Urolithiasis， 2018，46（4）：313-323. doi:10.1007/s00240-017-0998-6 doi: 10.1007/s00240-017-0998-6
20	MILLER A W， OAKESON K F， DALE C， et al. Microbial Community Transplant Results in Increased and Long-Term Oxalate Degradation［J］. Microb Ecol， 2016，72（2）：470-478. doi:10.1007/s00248-016-0800-2 doi: 10.1007/s00248-016-0800-2
21	MILLER A W， DALE C， DEARING M D. The Induction of Oxalate Metabolism In Vivo Is More Effective with Functional Microbial Communities than with Functional Microbial Species［J］. mSystems， 2017，2（5）：e00088-17. doi:10.1128/msystems.00088-17 doi: 10.1128/msystems.00088-17
22	SIDHU H， ALLISON M J， CHOW J O M， et al. Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes［J］. J Urol， 2001，166（4）：1487-1491. doi:10.1016/s0022-5347(05)65817-x doi: 10.1016/s0022-5347(05)65817-x
23	SALAZAR N， DE LOS REYES-GAVILÁN C G. Editorial： Insights into Microbe-Microbe Interactions in Human Microbial Ecosystems： Strategies to Be Competitive［J］. Front Microbiol， 2016，7：1508. doi:10.3389/fmicb.2016.01508 doi: 10.3389/fmicb.2016.01508
24	GREEN J E， DAVIS J A， BERK M， et al. Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection： a systematic review and meta-analysis［J］. Gut Microbes， 2020，12（1）：1-25. doi:10.1080/19490976.2020.1854640 doi: 10.1080/19490976.2020.1854640
25	STERN J M， URBAN-MALDONADO M， USYK M， et al. Fecal transplant modifies urine chemistry risk factors for urinary stone disease［J］. Physiol Rep， 2019，7（4）：e14012. doi:10.14814/phy2.14012 doi: 10.14814/phy2.14012
26	MILLER A W， CHOY D， PENNISTON K L， et al. Inhibition of urinary stone disease by a multi-species bacterial network ensures healthy oxalate homeostasis［J］. Kidney Int， 2019，96（1）：180-188. doi:10.1016/j.kint.2019.02.012 doi: 10.1016/j.kint.2019.02.012
27	张建清，王庆，江克华，等. microRNA在肾结石疾病中的作用机制和研究进展［J］. 实用医学杂志， 2023，39（6）：773-777. doi:10.3969/j.issn.1006-5725.2023.06.021 doi: 10.3969/j.issn.1006-5725.2023.06.021

引物名称	5′→3′
GAPDH	F：TGCCAAGTATGATGACATCAAGAA
GAPDH	R：AGCCCAGGATGCCCTTTAGT
OPN	F：TGAGACTGGCAGTGGTTTGC
OPN	R：CCACTTTCACCGGGAGACA
Renin	F：ACCAGGGCAACTTTCACTACGT
Renin	R：ACCCCCTTCATGGTGATCTG
ACE	F：TTGTCTGTCACTGGAGCCTGAT
ACE	R：CACACCCAAAGCAATTCTTCGT

指标	SC组	OD+PBS组	P值^a	OD + FMT组	P值^b
尿草酸	0.70 ± 0.05	0.96 ± 0.06	< 0.001	0.77 ± 0.04	< 0.001
尿素（μmol/L）	281.81 ± 31.66	420.33 ± 36.13	< 0.001	293.45 ± 26.46	< 0.001
尿酸（mmol/L）	0.18 ± 0.04	0.47 ± 0.07	< 0.001	0.33 ± 0.04	< 0.001
尿肌酐（mmol/L）	1.94 ± 0.54	4.10 ± 0.75	< 0.001	3.25 ± 0.50	0.03
血尿酸（μmol/L）	54.87 ± 14.44	79.04 ± 10.50	0.004	66.06 ± 12.00	0.09
血清尿素氮/肌酐	41.04 ± 4.14	53.83 ± 7.22	0.002	44.50 ± 6.22	0.02

Protective role of intestinal microbial network in hyperoxaluria⁃induced kidney impairment in rats

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