Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study

Carley Rusch, Matthew Beke, Lily Tucciarone, Carmelo Nieves Jr, Maria Ukhanova, Massimiliano S Tagliamonte, Volker Mai, Joon Hyuk Suh, Yu Wang, Shannon Chiu, Bhavana Patel, Adolfo Ramirez-Zamora, Bobbi Langkamp-Henken, Carley Rusch, Matthew Beke, Lily Tucciarone, Carmelo Nieves Jr, Maria Ukhanova, Massimiliano S Tagliamonte, Volker Mai, Joon Hyuk Suh, Yu Wang, Shannon Chiu, Bhavana Patel, Adolfo Ramirez-Zamora, Bobbi Langkamp-Henken

Abstract

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities. Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples. Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention. Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03851861.

Keywords: Mediterranean diet; Parkinson's disease; constipation; intestinal permeability; microbiota.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Rusch, Beke, Tucciarone, Nieves, Ukhanova, Tagliamonte, Mai, Suh, Wang, Chiu, Patel, Ramirez-Zamora and Langkamp-Henken.

Figures

Figure 1
Figure 1
Heat-map of prevalent bacterial OTUs (determined by z-score) with 95% similarity at baseline between control (n = 8) and PD groups (n = 8) and changes after a 5-week Mediterranean diet intervention (PD group; n = 8). (A) OTUs that were more prevalent in the control group compared to PD group at baseline. (B) OTUs that were more prevalent in the PD group compared to control group at baseline. (C) OTUs that decreased after the Mediterranean diet intervention in the PD group.

References

    1. Hess CW, Okun MS. Diagnosing Parkinson's disease. Continuum (Minneap Minn). (2016) 22:1047–63. 10.1212/CON.0000000000000345
    1. Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson's disease. Nat Rev Neurosci. (2017) 18:509. 10.1038/nrn.2017.62
    1. Knudsen K, Fedorova TD, Bekker AC, Iversen P, Østergaard K, Krogh K, et al. . Objective colonic dysfunction is far more prevalent than subjective constipation in parkinson's disease: a colon transit and volume study. J Parkinsons Dis. (2017) 7:359–67. 10.3233/JPD-161050
    1. Kaye J, Gage H, Kimber A, Storey L, Trend P. Excess burden of constipation in Parkinson's disease: a pilot study. Mov Disord. (2006) 21:1270–3. 10.1002/mds.20942
    1. Rahman S, Griffin HJ, Quinn NP, Jahanshahi M. Quality of life in Parkinson's disease: the relative importance of the symptoms. Mov Disord. (2008) 23:1428–34. 10.1002/mds.21667
    1. Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, et al. . Intestinal permeability—a new target for disease prevention and therapy. BMC Gastroenterol. (2014) 14:189. 10.1186/s12876-014-0189-7
    1. Davies KN, King D, Billington D, Barrett JA. Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease. Postgrad Med J. (1996) 72:164–7. 10.1136/pgmj.72.845.164
    1. Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, et al. . Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS ONE. (2011) 6:e28032. 10.1371/journal.pone.0028032
    1. Clairembault T, Leclair-Visonneau L, Coron E, Bourreille A, Le Dily S, Vavasseur F, et al. . Structural alterations of the intestinal epithelial barrier in Parkinson's disease. Acta Neuropathol Commun. (2015) 3:12. 10.1186/s40478-015-0196-0
    1. Mulak A, Koszewicz M, Panek-Jeziorna M, Koziorowska-Gawron E, Budrewicz S. Fecal calprotectin as a marker of the gut immune system activation is elevated in Parkinson's disease. Front Neurosci. (2019) 13:992. 10.3389/fnins.2019.00992
    1. Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Bürmann J, Faßbender K, et al. . Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. (2018) 50:104–7. 10.1016/j.parkreldis.2018.02.022
    1. Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, et al. . Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. (1995) 61(6 Suppl.):1402s−6. 10.1093/ajcn/61.6.1402S
    1. Peng L, Li ZR, Green RS, Holzman IR, Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr. (2009) 139:1619–25. 10.3945/jn.109.104638
    1. Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. (2011) 3:858–76. 10.3390/nu3100858
    1. Garcia-Mantrana I, Selma-Royo M, Alcantara C, Collado MC. Shifts on gut microbiota associated to mediterranean diet adherence and specific dietary intakes on general adult population. Front Microbiol. (2018) 9:890. 10.3389/fmicb.2018.00890
    1. De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, et al. . High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. (2016) 65:1812–21. 10.1136/gutjnl-2015-309957
    1. Gutiérrez-Díaz I, Fernández-Navarro T, Sánchez B, Margolles A, González S. Mediterranean diet and faecal microbiota: a transversal study. Food Funct. (2016) 7:2347–56. 10.1039/C6FO00105J
    1. Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, et al. . Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. (2020) 69:1218–28. 10.1136/gutjnl-2019-319654
    1. Shen T, Yue Y, He T, Huang C, Qu B, Lv W, et al. . The Association between the gut microbiota and Parkinson's disease, a meta-analysis. Front Aging Neurosci. (2021) 13:636545. 10.3389/fnagi.2021.636545
    1. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, et al. . Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord. (2016) 32:66–72. 10.1016/j.parkreldis.2016.08.019
    1. Heaton KW, Radvan J, Cripps H, Mountford RA, Braddon FE, Hughes AO. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut. (1992) 33:818–24. 10.1136/gut.33.6.818
    1. Svedlund J, Sjödin I, Dotevall G. GSRS–a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. (1988) 33:129–34. 10.1007/BF01535722
    1. Subar AF, Kirkpatrick SI, Mittl B, Zimmerman TP, Thompson FE, Bingley C, et al. . The Automated Self-Administered 24-hour dietary recall (ASA24): a resource for researchers, clinicians, and educators from the National Cancer Institute. J Acad Nutr Diet. (2012) 112:1134–7. 10.1016/j.jand.2012.04.016
    1. Papadaki A, Johnson L, Toumpakari Z, England C, Rai M, Toms S, et al. . Validation of the english version of the 14-item mediterranean diet adherence screener of the predimed study, in people at high cardiovascular risk in the UK. Nutrients. (2018) 10:138. 10.3390/nu10020138
    1. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. . Movement disorder society-sponsored revision of the unified Parkinson's disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. (2008) 23:2129–70. 10.1002/mds.22340
    1. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. . The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. (2005) 53:695–9. 10.1111/j.1532-5415.2005.53221.x
    1. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. . Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. (2018) 378:e34. 10.1056/NEJMoa1800389
    1. van Wijck K, van Eijk HM, Buurman WA, Dejong CH, Lenaerts K. Novel analytical approach to a multi-sugar whole gut permeability assay. J Chromatogr B Analyt Technol Biomed Life Sci. (2011) 879:2794–801. 10.1016/j.jchromb.2011.08.002
    1. 172.829 Neotame: Code of Fedral Regulations. (2002). Available online at: (accessed Jul 9, 2021).
    1. van Wijck K, Verlinden TJM, van Eijk HMH, Dekker J, Buurman WA, Dejong CHC, et al. . Novel multi-sugar assay for site-specific gastrointestinal permeability analysis: a randomized controlled crossover trial. Clin Nutr. (2013) 32:245–51. 10.1016/j.clnu.2012.06.014
    1. Miller DN, Bryant JE, Madsen EL, Ghiorse WC. Evaluation and optimization of DNA extraction and purification procedures for soil and sediment samples. Appl Environ Microbiol. (1999) 65:4715–24. 10.1128/AEM.65.11.4715-4724.1999
    1. Burns AM, Zitt MA, Rowe CC, Langkamp-Henken B, Mai V, Nieves C, Jr., et al. . Diet quality improves for parents and children when almonds are incorporated into their daily diet: a randomized, crossover study. Nutr Res. (2016) 36:80–9. 10.1016/j.nutres.2015.11.004
    1. Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. . Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. (2019) 37:852–7. 10.1038/s41587-019-0209-9
    1. Amir A, McDonald D, Navas-Molina JA, Kopylova E, Morton JT, Xu ZZ, et al. . Deblur rapidly resolves single-nucleotide community sequence patterns. mSystems. (2017) 2:e00191–16. 10.1128/mSystems.00191-16
    1. Rognes T, Flouri T, Nichols B, Quince C, Mahé F, VSEARCH . a versatile open source tool for metagenomics. PeerJ. (2016) 4:e2584. 10.7717/peerj.2584
    1. Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, et al. . Scikit-learn: machine learning in python. J Mach Learn Res. (2011) 12:2825–30. 10.5555/1953048.2078195
    1. DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, et al. . Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. (2006) 72:5069–72. 10.1128/AEM.03006-05
    1. Price MN, Dehal PS, Arkin AP. FastTree 2–approximately maximum-likelihood trees for large alignments. PLoS ONE. (2010) 5:e9490. 10.1371/journal.pone.0009490
    1. Eakin EG, Lawler SP, Vandelanotte C, Owen N. Telephone interventions for physical activity and dietary behavior change: a systematic review. Am J Prev Med. (2007) 32:419–34. 10.1016/j.amepre.2007.01.004
    1. Jonnalagadda SS, Mitchell DC, Smiciklas-Wright H, Meaker KB, Van Heel N, Karmally W, et al. . Accuracy of energy intake data estimated by a multiple-pass, 24-hour dietary recall technique. J Am Diet Assoc. (2000) 100:303–8. 10.1016/S0002-8223(00)00095-X
    1. Mancini JG, Filion KB, Atallah R, Eisenberg MJ. Systematic review of the mediterranean diet for long-term weight loss. Am J Med. (2016) 129:407–15.e4. 10.1016/j.amjmed.2015.11.028
    1. Ma K, Xiong N, Shen Y, Han C, Liu L, Zhang G, et al. . Weight loss and malnutrition in patients with Parkinson's disease: current knowledge and future prospects. Front Aging Neurosci. (2018) 10:1. 10.3389/fnagi.2018.00001
    1. Wills AM, Pérez A, Wang J, Su X, Morgan J, Rajan SS, et al. . association between change in body mass index, unified Parkinson's disease rating scale scores, and survival among persons with Parkinson's disease: secondary analysis of longitudinal data from NINDS exploratory trials in Parkinson's disease long-term study 1. JAMA Neurol. (2016) 73:321–8. 10.1001/jamaneurol.2015.4265
    1. Vriesman MH, Koppen IJN, Camilleri M, Di Lorenzo C, Benninga MA. Management of functional constipation in children and adults. Nat Rev Gastroenterol Hepatol. (2020) 17:21–39. 10.1038/s41575-019-0222-y
    1. Barichella M, Pacchetti C, Bolliri C, Cassani E, Iorio L, Pusani C, et al. . Probiotics and prebiotic fiber for constipation associated with Parkinson's disease: an RCT. Neurology. (2016) 87:1274–80. 10.1212/WNL.0000000000003127
    1. Pedrosa Carrasco AJ, Timmermann L, Pedrosa DJ. Management of constipation in patients with Parkinson's disease. NPJ Parkinsons Dis. (2018) 4:6. 10.1038/s41531-018-0042-8
    1. Salat-Foix D, Tran K, Ranawaya R, Meddings J, Suchowersky O. Increased intestinal permeability and Parkinson's disease patients: chicken or egg? Can J Neurol Sci. (2012) 39:185–8. 10.1017/S0317167100013202
    1. Chassard C, Dapoigny M, Scott KP, Crouzet L, Del'homme C, Marquet P, et al. . Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther. (2012) 35:828–38. 10.1111/j.1365-2036.2012.05007.x
    1. Kumari R, Ahuja V, Paul J. Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India. World J Gastroenterol. (2013) 19:3404. 10.3748/wjg.v19.i22.3404
    1. Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A. Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis. (2021) 7:27. 10.1038/s41531-021-00156-z
    1. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. . Induction of colonic regulatory T cells by indigenous Clostridium species. Science. (2011) 331:337–41. 10.1126/science.1198469
    1. La Rosa SL, Leth ML, Michalak L, Hansen ME, Pudlo NA, Glowacki R, et al. . The human gut Firmicute Roseburia intestinalis is a primary degrader of dietary β-mannans. Nat Commun. (2019) 10:905. 10.1038/s41467-019-08812-y
    1. Carbonero F, Benefiel A, Alizadeh-Ghamsari A, Gaskins HR. Microbial pathways in colonic sulfur metabolism and links with health and disease. Front Physiol. (2012) 3:448. 10.3389/fphys.2012.00448
    1. Baldini F, Hertel J, Sandt E, Thinnes CC, Neuberger-Castillo L, Pavelka L, et al. . Parkinson's disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC Biol. (2020) 18:62. 10.1101/691030
    1. Hertel J, Harms AC, Heinken A, Baldini F, Thinnes CC, Glaab E, et al. . Integrated analyses of microbiome and longitudinal metabolome data reveal microbial-host interactions on sulfur metabolism in Parkinson's disease. Cell Rep. (2019) 29:1767–77.e8. 10.1016/j.celrep.2019.10.035
    1. Cirstea MS Yu AC, Golz E, Sundvick K, Kliger D, Radisavljevic N, et al. . Microbiota composition and metabolism are associated with gut function in Parkinson's disease. Mov Disord. (2020) 35:1208–17. 10.1002/mds.28052
    1. Arrigoni E, Brouns F, Amadò R. Human gut microbiota does not ferment erythritol. Br J Nutr. (2005) 94:643–6. 10.1079/BJN20051546

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