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Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation

Published:September 29, 2022DOI:https://doi.org/10.1016/j.pmn.2022.08.013

      Abstract

      Background

      Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation.

      Aims

      Characterize associations between gut microbiome features and pain interference before and after kidney transplantation.

      Design

      Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant.

      Setting

      Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System.

      Participants/subjects

      19 living donor kidney transplant recipients.

      Methods

      We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57.

      Results

      We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene.

      Conclusions

      Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.
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      References

        • Ahmad S.
        • Bromberg J.S.
        Current status of the microbiome in renal transplantation.
        Curr Opin Nephrol Hypertens. 2016; 25: 570-576
        • Amro A.
        • Waldum B.
        • Dammen T.
        • Miaskowski C.
        • Os I.
        Symptom clusters in patients on dialysis and their association with quality-of-life outcomes.
        J Ren Care. 2014; 40: 23-33
        • Amro A.
        • Waldum-Grevbo B.
        • von der Lippe N.
        • Brekke F.B.
        • Miaskowski C.
        • Os I.
        Symptom clusters from dialysis to renal transplantation: A five-year longitudinal study.
        Journal of Pain and Symptom Management. 2016; 51: 512-519
        • Anders H.J.
        • Andersen K.
        • Stecher B.
        The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease.
        Kidney Int. 2013; 83: 1010-1016
        • Ardalan M.
        • Vahed S.Z.
        Gut microbiota and renal transplant outcome.
        Biomed Pharmacother. 2017; 90: 229-236
        • Arries C.
        • Ferrieri P.
        Mobiluncus  curtisii Bacteremia: Case study and literature review.
        Infect Dis Rep. 2022; 14: 82-87
        • Bartman C.
        • Chong A.S.
        • Alegre M.L.
        The influence of the microbiota on the immune response to transplantation.
        Curr Opin Organ Transplant. 2015; 20: 1-7
        • Benjamini Y.
        • Hochberg Y.
        Controlling the false discovery rate: A practical and powerful approach to multiple testing.
        Journal of the Royal Statistical Society. Series B (Methodological). 1995; 57: 289-300
        • Boer C.G.
        • Radjabzadeh D.
        • Medina-Gomez C.
        • Garmaeva S.
        • Schiphof D.
        • Arp P.
        • Koet T.
        • Kurilshikov A.
        • Fu J.
        • Ikram M.A.
        • Bierma-Zeinstra S.
        • Uitterlinden A.G.
        • Kraaij R.
        • Zhernakova A.
        • van Meurs J.B.J.
        Intestinal microbiome composition and its relation to joint pain and inflammation.
        Nat Commun. 2019; 10: 4881
        • Buchfink B.
        • Xie C.
        • Huson D.H
        Fast and sensitive protein alignment using DIAMOND.
        Nature Methods. 2014; (Advance online publication)
        • Chelakkot C.
        • Ghim J.
        • Ryu S.H.
        Mechanisms regulating intestinal barrier integrity and its pathological implications.
        Experimental & Molecular Medicine. 2018; 50: 1-9
        • Chen C.X.
        • Kroenke K.
        • Stump T.E.
        • Kean J.
        • Carpenter J.S.
        • Krebs E.E.
        • Bair M.J.
        • Damush T.M.
        • Monahan P.O.
        Estimating minimally important differences for the PROMIS pain interference scales: results from 3 randomized clinical trials.
        Pain. 2018; 159: 775-782
        • Cruz-Aguliar R.M.
        • Wantia N.
        • Clavel T.
        • Vehreschild M.
        • Buch T.
        • Bajbouj M.
        • Haller D.
        • Busch D.
        • Schmid R.M.
        • Stein-Thoeringer C.K.
        An open-labeled study on fecal microbiota transfer in irritable bowel syndrome patients reveals improvement in abdominal pain associated with the relative abundance of akkermansia muciniphila.
        Digestion. 2019; 100: 127-138
        • de Groot I.B.
        • Veen J.I.
        • van der Boog P.J.
        • van Dijk S.
        • Stiggelbout A.M.
        • Marang-van de Mheen P.J.
        Difference in quality of life, fatigue and societal participation between living and deceased donor kidney transplant recipients.
        Clin Transplant. 2013; 27: E415-E423
        • Ferrer M.
        • Ruiz A.
        • Lanza F.
        • Haange S.B.
        • Oberbach A.
        • Till H.
        • Bargiela R.
        • Campoy C.
        • Segura M.T.
        • Richter M.
        • von Bergen M.
        Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure.
        Environmental Microbiology. 2013; 15: 211-226
        • Fricke W.F.
        • Maddox C.
        • Song Y.
        • Bromberg J.S.
        Human microbiota characterization in the course of renal transplantation.
        Am J Transplant. 2014; 14: 416-427
        • Guo R.
        • Chen L.H.
        • Xing C.
        • Liu T.
        Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential.
        Br J Anaesth. 2019; 123: 637-654
        • Hays R.D.
        • Kallich J.D.
        • Mapes D.L.
        • Coons S.J.
        • Carter W.B.
        Development of the kidney disease quality of life (KDQOL) instrument.
        Qual Life Res. 1994; 3: 329-338
      1. HealthMeasures. (2022a). PROMIS® score cut points. Retrieved June 12, 2022, from https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis/promis-score-cut-points

      2. HealthMeasures. (2022b). Scoring instructions Retrieved June 12, 2022, from https://www.healthmeasures.net/index.php?option=com_content&view=category&layout=blog&id=190&Itemid=1214

        • Horton L.E.
        • Mehta S.R.
        • Aganovic L.
        • Fierer J.
        Actinotignum schaalii Infection: A Clandestine Cause of Sterile Pyuria?.
        Open Forum Infectious Diseases. 2018; 5 (ofy015)
        • Kanehisa M.
        • Furumichi M.
        • Tanabe M.
        • Sato Y.
        • Morishima K.
        KEGG: New perspectives on genomes, pathways, diseases and drugs.
        Nucleic Acids Res. 2017; 45: D353-D361
        • Karu N.
        • McKercher C.
        • Nichols D.S.
        • Davies N.
        • Shellie R.A.
        • Hilder E.F.
        • Jose M.D.
        Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study.
        BMC Nephrol. 2016; 17: 171
        • Kau A.L.
        • Ahern P.P.
        • Griffin N.W.
        • Goodman A.L.
        • Gordon J.I.
        Human nutrition, the gut microbiome and the immune system.
        Nature. 2011; 474: 327-336
        • Kimmel P.L.
        • Cohen S.D.
        • Weisbord S.D.
        Quality of life in patients with end-stage renal disease treated with hemodialysis: survival is not enough!.
        J Nephrol. 2008; 21: S54-S58
        • Lambourg E.
        • Colvin L.
        • Guthrie G.
        • Murugan K.
        • Lim M.
        • Walker H.
        • Boon G.
        • Bell S.
        The prevalence of pain among patients with chronic kidney disease using systematic review and meta-analysis.
        Kidney Int. 2021; 100: 636-649
        • Lee J.R.
        • Muthukumar T.
        • Dadhania D.
        • Taur Y.
        • Jenq R.R.
        • Toussaint N.C.
        • Ling L.
        • Pamer E.
        • Suthanthiran M.
        Gut microbiota and tacrolimus dosing in kidney transplantation.
        PLoS One. 2015; 10e0122399
        • Lee J.R.
        • Muthukumar T.
        • Dadhania D.
        • Toussaint N.C.
        • Ling L.
        • Pamer E.
        • Suthanthiran M.
        Gut microbial community structure and complications after kidney transplantation: a pilot study.
        Transplantation. 2014; 98: 697-705
        • Lockwood M.B.
        • Chung S.
        • Puzantian H.
        • Bronas U.G.
        • Ryan C.J.
        • Park C.
        • DeVon H.A.
        Symptom cluster science in chronic kidney disease: A literature review.
        West J Nurs Res. 2019; 41: 1056-1091
        • Martin C.R.
        • Osadchiy V.
        • Kalani A.
        • Mayer E.A.
        The Brain-Gut-Microbiome Axis.
        Cell Mol Gastroenterol Hepatol. 2018; 6: 133-148
        • McCarthy D.J.
        • Chen Y.
        • Smyth G.K.
        Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation.
        Nucleic Acids Res. 2012; 40: 4288-4297
        • Meier-Kriesche H.U.
        • Schold J.D.
        • Srinivas T.R.
        • Kaplan B.
        Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era.
        Am J Transplant. 2004; 4: 378-383
        • Minerbi A.
        • Gonzalez E.
        • Brereton N.J.B.
        • Anjarkouchian A.
        • Dewar K.
        • Fitzcharles M.A.
        • Chevalier S.
        • Shir Y.
        Altered microbiome composition in individuals with fibromyalgia.
        Pain. 2019; 160: 2589-2602
        • Murphy E.C.
        • Frick I.-M.
        Gram-positive anaerobic cocci – commensals and opportunistic pathogens.
        FEMS Microbiology Reviews. 2013; 37: 520-553
        • Nourbala M.H.
        • Hollisaaz M.T.
        • Nasiri M.
        • Bahaeloo-Horeh S.
        • Najafi M.
        • Araghizadeh H.
        • Rezaie Y.
        • Lak M.
        Pain affects health-related quality of life in kidney transplant recipients.
        Transplant Proc. 2007; 39: 1126-1129
      3. Oksanen, J., Blanchet, F. G., Friendly, M., Kindt, R., Legendre, P., McGlinn, D., Minchin, P. R., O'Hara, R. B., Simpson, G. L., Solymos, P., Stevens, M. H. H., Szoecs, E., & Wagner, H. (2018). vegan: Community Ecology Package. 2.4.0 [Computer software].

        • Ramakrishna C.
        • Corleto J.
        • Ruegger P.M.
        • Logan G.D.
        • Peacock B.B.
        • Mendonca S.
        • Yamaki S.
        • Adamson T.
        • Ermel R.
        • McKemy D.
        • Borneman J.
        • Cantin E.M.
        Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain.
        Sci Rep. 2019; 9: 20324
        • Rea K.
        • O'Mahony S.M.
        • Dinan T.G.
        • Cryan J.F.
        The role of the gastrointestinal microbiota in visceral pain.
        Handb Exp Pharmacol. 2017; 239: 269-287
        • Roy P.J.
        • Weltman M.
        • Dember L.M.
        • Liebschutz J.
        • Jhamb M.
        Pain management in patients with chronic kidney disease and end-stage kidney disease.
        Curr Opin Nephrol Hypertens. 2020; 29: 671-680
        • Schwebke J.R.
        • Morgan S.C.
        • Hillier S.L.
        Humoral antibody to Mobiluncus curtisii, a potential serological marker for bacterial vaginosis.
        Clin Diagn Lab Immunol. 1996; 3: 567-569
        • Sherwin E.
        • Rea K.
        • Dinan T.G.
        • Cryan J.F.
        A gut (microbiome) feeling about the brain.
        Curr Opin Gastroenterol. 2016; 32: 96-102
        • Song B.C.
        • Bai J.
        Microbiome-gut-brain axis in cancer treatment-related psychoneurological toxicities and symptoms: a systematic review.
        Support Care Cancer. 2021; 29: 605-617
        • Tang E.
        • Ekundayo O.
        • Peipert J.D.
        • Edwards N.
        • Bansal A.
        • Richardson C.
        • Bartlett S.J.
        • Howell D.
        • Li M.
        • Cella D.
        • Novak M.
        • Mucsi I.
        Validation of the Patient-Reported Outcomes Measurement Information System (PROMIS)-57 and -29 item short forms among kidney transplant recipients.
        Qual Life Res. 2019; 28: 815-827
        • Tarlov A.R.
        • Ware Jr., J.E.
        • Greenfield S.
        • Nelson E.C.
        • Perrin E.
        • Zubkoff M
        The Medical Outcomes Study. An application of methods for monitoring the results of medical care.
        JAMA. 1989; 262: 925-930
        • Taylor K.
        • Chu N.M.
        • Chen X.
        • Shi Z.
        • Rosello E.
        • Kunwar S.
        • Butz P.
        • Norman S.P.
        • Crews D.C.
        • Greenberg K.I.
        • Mathur A.
        • Segev D.L.
        • Shafi T.
        • McAdams-DeMarco M.A.
        Kidney disease symptoms before and after kidney transplantation.
        Clin J Am Soc Nephrol. 2021; 16: 1083-1093
        • The UniProt Consortium
        UniProt: The universal protein knowledgebase.
        Nucleic Acids Res. 2017; 45: D158-D169
        • Tonelli M.
        • Wiebe N.
        • Knoll G.
        • Bello A.
        • Browne S.
        • Jadhav D.
        • Klarenbach S.
        • Gill J.
        Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes.
        Am J Transplant. 2011; 11: 2093-2109
        • Ursell L.K.
        • Metcalf J.L.
        • Parfrey L.W.
        • Knight R.
        Defining the human microbiome.
        Nutr Rev. 2012; 70: S38-S44
        • Victoria M.
        • Elena V.-D.B.
        • Amparo G.-G.N.
        • María J.-R.A.
        • Adriana G.-V.
        • Irene A.-C.
        • Alejandra Y.-M.M.
        • Janeth B.-B.
        • María A.-O.G.
        Gut microbiota alterations in critically ill older patients: a multicenter study.
        BMC Geriatrics. 2022; 22: 373
        • Vindigni S.M.
        • Surawicz C.M.
        The gut microbiome: A clinically significant player in transplantation?.
        Expert Rev Clin Immunol. 2015; 11: 781-783
        • Wang Q.
        • Huang S.-Q.
        • Li C.-Q.
        • Xu Q.
        • Zeng Q.-P.
        Akkermansia muciniphila may determine chondroitin sulfate ameliorating or aggravating osteoarthritis.
        Front Microbiol. 2017; 8
        • Weisbord S.D.
        Patient-centered dialysis care: depression, pain, and quality of life.
        Semin Dial. 2016; 29: 158-164
        • Wickham H.
        ggplot2: Elegant graphics for data analysis.
        Springer, New York2009
        • Yang J.
        • Reilly B.G.
        • Davis T.P.
        • Ronaldson P.T.
        Modulation of opioid transport at the blood-brain barrier by altered atp-binding cassette (ABC) transporter expression and activity.
        Pharmaceutics. 2018; 10: 192
        • Yin J.
        • Song Y.
        • Hu Y.
        • Wang Y.
        • Zhang B.
        • Wang J.
        • Ji X.
        • Wang S.
        Dose-dependent beneficial effects of tryptophan and its derived metabolites on Akkermansia in vitro: A preliminary prospective study.
        Microorganisms. 2021; 9: 1511
        • Zaza G.
        • Dalla Gassa A.
        • Felis G.
        • Granata S.
        • Torriani S.
        • Lupo A.
        Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.
        PLoS One. 2017; 12e0178228