Abstract
Rationale
Although a growing body of evidence indicates that the scores of cognitive function in hemodialysis patients are significantly lower than those of healthy individuals, underlying mechanisms have not been fully elucidated.
Objectives
To investigate the roles of gut microbiota and serum metabolites in hemodialysis patients with mild cognitive decline (MCD).
Methods
A total of 30 healthy individuals and 77 hemodialysis patients were enrolled and were classified into healthy control (HC), normal cognitive function (NCF), and MCD groups by evaluation of Montreal Cognitive Assessment. Fecal samples were analyzed by 16S rRNA and serum samples were analyzed by gas chromatography-mass spectrometry from all subjects.
Results
The 16S rRNA study demonstrated that the gut microbiota profiles, including α- and β-diversity, and a number of 16 gut bacteria were significantly altered in the MCD group compared with those in HC or those with NCF. A metabonomics study showed that a total of 29 serum metabolites were altered in the MCD group. Receiver operating characteristic curves showed that Genus Bilophila and serum putrescine might be sensitive biomarkers to indicate MCD in patients with hemodialysis.
Conclusions
These findings demonstrate gut microbiota and serum metabolites were probably involved in the pathogenesis of hemodialysis-related MCD. Therapeutic strategies targeting abnormalities in gut microbiota and serum metabolites may facilitate the beneficial effects for hemodialysis patients with MCD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akerfeldt S (1957) Oxidation of N, N-dimethyl-p-phenylenediamine by serum from patients with mental disease. Science 125:117–119. https://doi.org/10.1126/science.125.3238.117
Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, Monteith P, Noble NA, Sikaroodi M, Gillevet PM (2012) Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol 303:G675–G685. https://doi.org/10.1152/ajpgi.00152.2012
Berger ML, Pohler T, Schadt O, Stanger M, Rebernik P, Scholze P, Noe CR (2013) Exploring the polyamine regulatory site of the NMDA receptor: a parallel synthesis approach. ChemMedChem 8:82–94. https://doi.org/10.1002/cmdc.201200470
Caplin B, Nitsch D (2017) Urinary biomarkers of tubular injury in chronic kidney disease. Kidney Int 91:21–23. https://doi.org/10.1016/j.kint.2016.10.003
Chen HJ, Qi R, Kong X, Wen J, Liang X, Zhang Z, Li X, Lu GM, Zhang LJ (2015) The impact of hemodialysis on cognitive dysfunction in patients with end-stage renal disease: a resting-state functional MRI study. Metab Brain Dis 30:1247–1256. https://doi.org/10.1007/s11011-015-9702-0
Chhabra YK, Sood S, Rathi O, Mahajan S (2017) Effect of renal transplantation on cognitive function in hemodialysis patients: a longitudinal study. Int Urol Nephrol 49:2071–2078. https://doi.org/10.1007/s11255-017-1700-1
Ciesielska N, Sokolowski R, Mazur E, Podhorecka M, Polak-Szabela A, Kedziora-Kornatowska K (2016) Is the Montreal Cognitive Assessment (MoCA) test better suited than the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) detection among people aged over 60? Meta-analysis. Psychiatr Pol 50:1039–1052. https://doi.org/10.12740/PP/45368
Collingridge GL, Volianskis A, Bannister N, France G, Hanna L, Mercier M, Tidball P, Fang G, Irvine MW, Costa BM, Monaghan DT, Bortolotto ZA, Molnar E, Lodge D, Jane DE (2013) The NMDA receptor as a target for cognitive enhancement. Neuropharmacology 64:13–26. https://doi.org/10.1016/j.neuropharm.2012.06.051
Dinan TG, Cryan JF (2017) The microbiome-gut-brain axis in health and disease. Gastroenterol Clin N Am 46:77–89. https://doi.org/10.1016/j.gtc.2016.09.007
Evenepoel P, Poesen R, Meijers B (2017) The gut-kidney axis. Pediatr Nephrol 32:2005–2014. https://doi.org/10.1007/s00467-016-3527-x
Fadili W, Al Adlouni A, Louhab N, Habib Allah M, Kissani N, Laouad I (2014) Prevalence and risk factors of cognitive dysfunction in chronic hemodialysis patients. Aging Ment Health 18:207–211. https://doi.org/10.1080/13607863.2013.823375
Forsgren L, Almay BG, Haggendal J, Oreland L (1987) Monoamine oxidase (MAO), 5-hydroxyindole acetic acid (5 HIAA) and homovanillic acid (HVA) in motor neuron disease. Acta Neurol Scand 75:22–27. https://doi.org/10.1111/j.1600-0404.1987.tb07884.x
Gareau MG (2014) Microbiota-gut-brain axis and cognitive function. Adv Exp Med Biol 817:357–371. https://doi.org/10.1007/978-1-4939-0897-4_16
Guivier E, Martin JF, Pech N, Ungaro A, Chappaz R, Gilles A (2018) Microbiota diversity within and between the tissues of two wild interbreeding species. Microb Ecol 75:799–810. https://doi.org/10.1007/s00248-017-1077-9
Gupta RS, Chen WJ, Adeolu M, Chai Y (2013) Molecular signatures for the class Coriobacteriia and its different clades; proposal for division of the class Coriobacteriia into the emended order Coriobacteriales, containing the emended family Coriobacteriaceae and Atopobiaceae fam. nov., and Eggerthellales ord. nov., containing the family Eggerthellaceae fam. nov. Int J Syst Evol Microbiol 63:3379–3397. https://doi.org/10.1099/ijs.0.048371-0
Halket JM, Przyborowska A, Stein SE, Mallard WG, Down S, Chalmers RA (1999) Deconvolution gas chromatography/mass spectrometry of urinary organic acids--potential for pattern recognition and automated identification of metabolic disorders. Rapid Commun Mass Spectrom 13:279–284. https://doi.org/10.1002/(SICI)1097-0231(19990228)13:4 < 279::AID-RCM478 > 3.0.CO;2-I
Hicks KA, Yuen ME, Zhen WF, Gerwig TJ, Story RW, Kopp MC, Snider MJ (2016) Structural and biochemical characterization of 6-hydroxynicotinic acid 3-monooxygenase, a novel decarboxylative hydroxylase involved in aerobic nicotinate degradation. Biochemistry 55:3432–3446. https://doi.org/10.1021/acs.biochem.6b00105
Himmelfarb J, Ikizler TA (2010) Hemodialysis. N Engl J Med 363:1833–1845. https://doi.org/10.1056/NEJMra0902710
Huang N, Hua D, Zhan G, Li S, Zhu B, Jiang R, Yang L, Bi J, Xu H, Hashimoto K, Luo A, Yang C (2019) Role of Actinobacteria and Coriobacteriia in the antidepressant effects of ketamine in an inflammation model of depression. Pharmacol Biochem Behav 176:93–100. https://doi.org/10.1016/j.pbb.2018.12.001
Jiang C, Li G, Huang P, Liu Z, Zhao B (2017) The gut microbiota and Alzheimer’s disease. J Alzheimers Dis 58:1–15. https://doi.org/10.3233/JAD-161141
Kind T, Wohlgemuth G, Lee DY, Lu Y, Palazoglu M, Shahbaz S, Fiehn O (2009) FiehnLib: mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Anal Chem 81:10038–10048. https://doi.org/10.1021/ac9019522
Kurella Tamura M, Yaffe K, Hsu CY, Yang J, Sozio S, Fischer M, Chen J, Ojo A, De Luca J, Xie D, Vittinghoff E, Go AS, Chronic Renal Insufficiency Cohort Study I (2016) Cognitive impairment and progression of CKD. Am J Kidney Dis 68:77–83. https://doi.org/10.1053/j.ajkd.2016.01.026
Li H, Cai J, Chen R, Zhao Z, Ying Z, Wang L, Chen J, Hao K, Kinney PL, Chen H, Kan H (2017) Particulate matter exposure and stress hormone levels: a randomized, double-blind, crossover trial of air purification. Circulation 136:618–627. https://doi.org/10.1161/CIRCULATIONAHA.116.026796
Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x
Neumann D, Mau W, Wienke A, Girndt M (2018) Peritoneal dialysis is associated with better cognitive function than hemodialysis over a one-year course. Kidney Int 93:430–438. https://doi.org/10.1016/j.kint.2017.07.022
O'Toole PW, Jeffery IB (2015) Gut microbiota and aging. Science 350:1214–1215. https://doi.org/10.1126/science.aac8469
Pan W, Kang Y (2018) Gut microbiota and chronic kidney disease: implications for novel mechanistic insights and therapeutic strategies. Int Urol Nephrol 50:289–299. https://doi.org/10.1007/s11255-017-1689-5
Parvez S, Abdel-Kader K, Song MK, Unruh M (2015) Conveying uncertainty in prognosis to patients with ESRD. Blood Purif 39:58–64. https://doi.org/10.1159/000368954
Romagnani P, Remuzzi G, Glassock R, Levin A, Jager KJ, Tonelli M, Massy Z, Wanner C, Anders HJ (2017) Chronic kidney disease. Nat Rev Dis Primers 3:17088. https://doi.org/10.1038/nrdp.2017.88
Seliger SL (2015) Frailty and cognitive impairment in ESRD: brain-body connections. Clin J Am Soc Nephrol 10:2104–2106. https://doi.org/10.2215/CJN.11321015
Sher L, Oquendo MA, Li S, Burke AK, Grunebaum MF, Zalsman G, Huang YY, Mann JJ (2005) Higher cerebrospinal fluid homovanillic acid levels in depressed patients with comorbid posttraumatic stress disorder. Eur Neuropsychopharmacol 15:203–209. https://doi.org/10.1016/j.euroneuro.2004.09.009
Tasmoc A, Donciu MD, Veisa G, Nistor I, Covic A (2016) Increased arterial stiffness predicts cognitive impairment in hemodialysis patients. Hemodial Int 20:463–472. https://doi.org/10.1111/hdi.12406
Tkachenko AG, Kashevarova NM, Karavaeva EA, Shumkov MS (2014) Putrescine controls the formation of Escherichia coli persister cells tolerant to aminoglycoside netilmicin. FEMS Microbiol Lett 361:25–33. https://doi.org/10.1111/1574-6968.12613
Wang H, Zhang L, Lv J (2005) Prevention of the progression of chronic kidney disease: practice in China. Kidney Int Suppl 67:S63–S67. https://doi.org/10.1111/j.1523-1755.2005.09416.x
Yang C, Qu Y, Fujita Y, Ren Q, Ma M, Dong C, Hashimoto K (2017) Possible role of the gut microbiota-brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model. Transl Psychiatry 7:1294. https://doi.org/10.1038/s41398-017-0031-4
Zhan G, Yang N, Li S, Huang N, Fang X, Zhang J, Zhu B, Yang L, Yang C, Luo A (2018) Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging (Albany NY) 10:1257–1267. https://doi.org/10.18632/aging.101464
Zhang A, Sun H, Wang X (2012) Serum metabolomics as a novel diagnostic approach for disease: a systematic review. Anal Bioanal Chem 404:1239–1245. https://doi.org/10.1007/s00216-012-6117-1
Zhu B, Jin LN, Shen JQ, Liu JF, Jiang RY, Yang L, Zhang J, Luo AL5, Miao LY, Yang C (2018) Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: a prospective single-center cohort study. Sci Rep 8:12250. https://doi.org/10.1038/s41598-018-29760-5
Funding
This study was supported by grants from the National Natural Science Foundation of China (to C.Y., 81703482 and 81974171) and was partially supported by the Program of Bureau of Science and Technology Foundation of Changzhou (to B.Z., CJ20159022; to L.M., CJ20179028) and Major Science and Technology Projects of Changzhou Municipal Committee of Health and Family Planning (to B.Z., ZD201505; to L.M., ZD201601). And we thank Shanghai OE Biotechnology Company for providing assistance in data analysis of 16S rRNA sequencing.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 1867 kb)
Rights and permissions
About this article
Cite this article
Zhu, B., Shen, J., Jiang, R. et al. Abnormalities in gut microbiota and serum metabolites in hemodialysis patients with mild cognitive decline: a single-center observational study. Psychopharmacology 237, 2739–2752 (2020). https://doi.org/10.1007/s00213-020-05569-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-020-05569-x