The role of small intestinal bacterial overgrowth in Parkinson's disease
Corresponding Author
Alfonso Fasano MD, PhD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Department of Neuroscience, AFaR-Fatebenefratelli Hospital, Rome, Italy
Correspondence to: Dr. Alfonso Fasano, Movement Disorders Centre – Toronto Western Hospital, 399 Bathurst St, 7 Mc412, Toronto, ON Canada M5T 2S8; [email protected]Search for more papers by this authorFrancesco Bove MD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorMaurizio Gabrielli MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorMartina Petracca MD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorMaria Assunta Zocco MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorEnzo Ragazzoni CBC, PhD
Department of Pharmacology, Catholic University of Sacred Heart, Rome, Italy
Search for more papers by this authorFederico Barbaro MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorCarla Piano MD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorSerena Fortuna CBC
Department of Pharmacology, Catholic University of Sacred Heart, Rome, Italy
Search for more papers by this authorAnnalisa Tortora MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorRaffaella Di Giacopo MD, PhD
Center for Neurocognitive Rehabilitation (CeRiN), Mind/Brain Sciences (CIMeC), Trento University, Rovereto, Italy
Search for more papers by this authorMariachiara Campanale MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorGiovanni Gigante MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorErnesto Cristiano Lauritano MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorPierluigi Navarra MD
Department of Pharmacology, Catholic University of Sacred Heart, Rome, Italy
Search for more papers by this authorStefano Marconi MD
Medical Direction, Chiesi Farmaceutici, Parma, Italy
Search for more papers by this authorAntonio Gasbarrini MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorAnna Rita Bentivoglio MD, PhD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorCorresponding Author
Alfonso Fasano MD, PhD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Department of Neuroscience, AFaR-Fatebenefratelli Hospital, Rome, Italy
Correspondence to: Dr. Alfonso Fasano, Movement Disorders Centre – Toronto Western Hospital, 399 Bathurst St, 7 Mc412, Toronto, ON Canada M5T 2S8; [email protected]Search for more papers by this authorFrancesco Bove MD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorMaurizio Gabrielli MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorMartina Petracca MD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorMaria Assunta Zocco MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorEnzo Ragazzoni CBC, PhD
Department of Pharmacology, Catholic University of Sacred Heart, Rome, Italy
Search for more papers by this authorFederico Barbaro MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorCarla Piano MD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorSerena Fortuna CBC
Department of Pharmacology, Catholic University of Sacred Heart, Rome, Italy
Search for more papers by this authorAnnalisa Tortora MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorRaffaella Di Giacopo MD, PhD
Center for Neurocognitive Rehabilitation (CeRiN), Mind/Brain Sciences (CIMeC), Trento University, Rovereto, Italy
Search for more papers by this authorMariachiara Campanale MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorGiovanni Gigante MD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorErnesto Cristiano Lauritano MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorPierluigi Navarra MD
Department of Pharmacology, Catholic University of Sacred Heart, Rome, Italy
Search for more papers by this authorStefano Marconi MD
Medical Direction, Chiesi Farmaceutici, Parma, Italy
Search for more papers by this authorAntonio Gasbarrini MD, PhD
Internal Medicine Department, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorAnna Rita Bentivoglio MD, PhD
Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy
Search for more papers by this authorRelevant conflicts of interest/financial disclosures: Nothing to report.
ABSTRACT
Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale–IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society
References
- 1Gasbarrini A, Lauritano EC, Gabrielli M, et al. Small intestinal bacterial overgrowth: diagnosis and treatment. Dig Dis. 2007; 25: 237–240.
- 2Zietz B, Lock G, Straub RH, Braun B, Scholmerich J, Palitzsch KD. Small-bowel bacterial overgrowth in diabetic subjects is associated with cardiovascular autonomic neuropathy. Diabetes Care. 2000; 23: 1200–1201.
- 3Lauritano EC, Bilotta AL, Gabrielli M, et al. Association between hypothyroidism and small intestinal bacterial overgrowth. J Clin Endocrinol Metab. 2007; 92: 4180–4184.
- 4Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol. 2003; 2: 107–116.
- 5Lewitan A, Nathanson L, Slade WR. Megacolon and dilatation of the small bowel in parkinsonism. Gastroenterology. 1952; 17: 367–374.
- 6Eaker EY, Bixler GB, Dunn AJ, Moreshead WV, Mathias JR. Chronic alterations in jejunal myoelectric activity in rats due to MPTP. Am J Physiol. 1987; 253: G809–G815.
- 7Gabrielli M, Bonazzi P, Scarpellini E, et al. Prevalence of small intestinal bacterial overgrowth in Parkinson's disease. Mov Disord. 2011; 26: 889–892.
- 8Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study. Brain. 2000; 123: 2297–2305.
- 9Colosimo C, De Michele M. Motor fluctuations in Parkinson's disease: pathophysiology and treatment. Eur J Neurol. 1999; 6: 1–21.
- 10Widnell K. Pathophysiology of motor fluctuations in Parkinson's disease. Mov Disord. 2005; 20(Suppl 11): S17–S22.
- 11Djaldetti R, Baron J, Ziv I, Melamed E. Gastric emptying in Parkinson's disease: patients with and without response fluctuations. Neurology. 1996; 46: 1051–1054.
- 12Pierantozzi M, Pietroiusti A, Brusa L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology. 2006; 66: 1824–1829.
- 13Lee WY, Yoon WT, Shin HY, Jeon SH, Rhee PL. Helicobacter pylori infection and motor fluctuations in patients with Parkinson's disease. Mov Disord. 2008; 23: 1696–1700.
- 14Lauritano EC, Gabrielli M, Scarpellini E, et al. Small intestinal bacterial overgrowth recurrence after antibiotic therapy. Am J Gastroenterol. 2008; 103: 2031–2035.
- 15Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999; 56: 33–39.
- 16Fahn S, Elton R, Committee. MotUD. Recent Developments in Parkinson's Disease. Folorham Park, NJ: Macmillan Health Care Information;1987.
- 17Hauser RA, Friedlander J, Zesiewicz TA, et al. A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia. Clin Neuropharmacol. 2000; 23: 75–81.
- 18Gasbarrini A, Corazza GR, Gasbarrini G, et al. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther. 2009; 29(Suppl 1): 1–49.
- 19Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008; 53: 1443–1454.
- 20Gisbert JP, Pajares JM. Review article: 13C-urea breath test in the diagnosis of Helicobacter pylori infection—a critical review. Aliment Pharmacol Ther. 2004; 20: 1001–1017.
- 21Defer GL, Widner H, Marie RM, Remy P, Levivier M. Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord. 1999; 14: 572–584.
- 22Lane RD, Glazer WM, Hansen TE, Berman WH, Kramer SI. Assessment of tardive dyskinesia using the Abnormal Involuntary Movement Scale. J Nerv Ment Dis. 1985; 173: 353–357.
- 23Bolondi L, Bortolotti M, Santi V, Calletti T, Gaiani S, Labo G. Measurement of gastric emptying time by real-time ultrasonography. Gastroenterology. 1985; 89: 752–759.
- 24Benini L, Sembenini C, Heading RC, et al. Simultaneous measurement of gastric emptying of a solid meal by ultrasound and by scintigraphy. Am J Gastroenterol. 1999; 94: 2861–2865.
- 25Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection—the Maastricht 2–2000 Consensus Report. Aliment Pharmacol Ther. 2002; 16: 167–180.
- 26Lang AE. A critical appraisal of the premotor symptoms of Parkinson's disease: potential usefulness in early diagnosis and design of neuroprotective trials. Mov Disord. 2011; 26: 775–783.
- 27Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett. 2006; 396: 67–72.
- 28Phillips RJ, Walter GC, Wilder SL, Baronowsky EA, Powley TL. Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: autonomic pathway implicated in Parkinson's disease? Neuroscience. 2008; 153: 733–750.
- 29Quigley EM. Microflora modulation of motility. J Neurogastroenterol Motil. 2011; 17: 140–147.
- 30Wullner U, Schmitz-Hubsch T, Antony G, et al. Autonomic dysfunction in 3414 Parkinson's disease patients enrolled in the German Network on Parkinson's disease (KNP e.V.): the effect of ageing. Eur J Neurol. 2007; 14: 1405–1408.
- 31Korchounov A, Kessler KR, Yakhno NN, Damulin IV, Schipper HI. Determinants of autonomic dysfunction in idiopathic Parkinson's disease. J Neurol. 2005; 252: 1530–1536.
- 32Bonuccelli U, Del Dotto P, Lucetti C, et al. Diurnal motor variations to repeated doses of levodopa in Parkinson's disease. Clin Neuropharmacol. 2000; 23: 28–33.
- 33Stocchi F, Fabbri L, Vecsei L, Krygowska-Wajs A, Monici Preti PA, Ruggieri SA. Clinical efficacy of a single afternoon dose of effervescent levodopa-carbidopa preparation (CHF 1512) in fluctuating Parkinson disease. Clin Neuropharmacol. 2007; 30: 18–24.
- 34Wanitschke R, Ammon HV. Effects of dihydroxy bile acids and hydroxy fatty acids on the absorption of oleic acid in the human jejunum. J Clin Invest. 1978; 61: 178–186.
- 35Nucera G, Gabrielli M, Lupascu A, et al. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2005; 21: 1391–1395.
- 36Lomax AE, Linden DR, Mawe GM, Sharkey KA. Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits. Auton Neurosci. 2006; 126–127: 250–257.
- 37Spencer RP. Intestinal absorption of amino acids. Current concepts. Am J Clin Nutr. 1969; 22: 292–299.
- 38Varcoe R, Haliday D, Tavill AS. Utilization of urea nitrogen for albumin synthesis in the stagnant loop syndrome. Gut. 1974; 15: 898–902.
- 39Barker HA. Amino acid degradation by anaerobic bacteria. Annu Rev Biochem. 1981; 50: 23–40.
- 40Belay T, Sonnenfeld G. Differential effects of catecholamines on in vitro growth of pathogenic bacteria. Life Sci. 2002; 71: 447–456.
- 41Gatto M, Fernandez Pardal M, Melero M, Zurru C, Scorticati C, Micheli F. L-dopa malabsorption in a parkinsonian patient with Strongyloides stercoralis duodenitis. Clin Neuropharmacol. 1994; 17: 96–98.
- 42Dobbs RJ, Charlett A, Dobbs SM, Weller C, Peterson DW. Parkinsonism: differential age-trend in Helicobacter pylori antibody. Aliment Pharmacol Ther. 2000; 14: 1199–1205.
- 43Minocha A, Mokshagundam S, Gallo SH, Rahal PS. Alterations in upper gastrointestinal motility in Helicobacter pylori-positive nonulcer dyspepsia. Am J Gastroenterol. 1994; 89: 1797–1800.
- 44Calam J. Helicobacter pylori modulation of gastric acid. Yale J Biol Med. 1999; 72: 195–202.
- 45Gasbarrini A, Gasbarrini G, Pelosini I, Scarpignato C. Eradication of Helicobacter pylori: are rifaximin-based regimens effective? Digestion. 2006; 73(Suppl 1): 129–135.
- 46Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord. 2010; 25: 2649–2653.
- 47Thompson WG, Drossman DA, Talley NJ, et al. Rome III diagnostic questionnaire for the adult functional GI disorders (including alarm questions) and scoring algorithm. In: DA Drossman, E Corazziari, M Delvaux, et al, eds. ROME III, the Functional Gastrointestinal Disorders. 3rd ed. McLean, VA: Degnon Associates; 2006: 917–951.