P2274 - Antibiotic Combination Therapy Improves Symptoms of Parkinson’s Disease in Individuals With Chronic Constipation

Award: Presidential Poster Award

Award: Presidential Poster Award

Rhys Collyer, BSc, Anoja W. Gunaratne, PhD, MSc, Annabel K. Clancy, PhD, Thomas J. Borody, MD, PhD, DSc, FRACP, FACG
Centre for Digestive Diseases, Five Dock, New South Wales, Australia

Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons with motor symptoms of tremor, rigidity, bradykinesia and postural instability alongside non-motor symptoms such as constipation. Here we explore the effects of a novel antibiotic combination therapy (ACT) comprising Metronidazole, Vancomycin and Rifaximin for the treatment of constipation, which improved symptoms of PD in two cases. Our findings were validated by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to rank the burden of disease ranging from normal=0 to most severe=272.

Case Description/Methods: Case 1 A 69 y/o male presented with PD and severe constipation including straining to initiate a bowel movement and inability to defecate for up to 1wk. Before commencing ACT, preliminary MDS-UPDRS was 38 and symptoms included asymmetric tremor, cogwheel rigidity, bradykinesia and shuffling gait despite treatment with Levodopa and Carbidopa. At 1yr review on ACT, constipation had abated with daily bowel motions not requiring Movicol. The MDS-UPDRS fell to 21 indicating a 45% reduction even with an unchanged PD medication regimen. Strikingly, there was a diminished tremor, milder cog-wheeling tone and minimal impairment of gait. After concluding ACT, the patient slowly regressed in line with the natural progression of disease.

Case 2 A 62 y/o female presented with PD and a 10yr history of constipation, passing a bowel motion once every 4d with bloating and flatulence. Before ACT with added Colchicine was commenced, baseline MDS-UPDRS was 37 and symptoms included asymmetric tremor, rigidity, postural instability and decreased arm swing despite treatment with Pramipexole and Rasagiline. At 1yr follow-up on ACT, constipation had resolved with complete emptying daily and no bloating or flatulence. The MDS-UPDRS fell to 26 denoting a 30% reduction whilst the dosage of PD medication remained constant. Noticeably, there was a decreased frequency of tremor, absence of rigidity, improved balance and greater arm swing. Upon cessation of ACT, the patient had a sustained response and gained further success with self-initiated thiamine injections.

Discussion: ACT successfully treated constipation and improved neurological symptoms of PD in two cases. Our findings suggest that treatments modulating the gut microbiota may play a role in reducing the severity and progression of PD as well as ameliorating non-motor symptoms such as constipation.

Demographics	Baseline			Treatment		Follow-up
Patient ID, Age, Gender, Diagnosis	PD Symptoms		MDS-UPDRS	PD Medication	Antibiotic Combination Therapy	PD Symptoms		MDS-UPDRS
	Motor	Non-motor				Motor	Non-motor
Pt. ID: #1 Age: 69 Gender: M Diagnosis: 2001	Tremor: Y Rigidity: Y Bradykinesia: Y Shuffling gait: Y Hypomimia: Y Hypophonia: Y Micrographia: Y	Constipation: Y (w Movicol, BNO 7/days) Dysfunctional sleep: Y Anosmia: Y	Part I = 5 Part II = 17 Part III = 11 Part IV = 5 Total = 38	Levodopa 100mg ii qid Carbidopa 25mg ii qid	Metronidazole 400mg i qd Vancomycin 250mg ii bd Rifaximin 500mg i bd	Tremor: Improved Rigidity: Improved Bradykinesia: Y Shuffling gait: Improved Hypomimia: Y Hypophonia: Y Micrographia: Y	Constipation: N (w/o Movicol, BO 1/day) Dysfunctional sleep: Improved Anosmia: Improved	Part I = 1 Part II = 7 Part III = 6 Part IV = 7 Total = 21
Pt. ID: #2 Age: 62 Gender: F Diagnosis: 2010	Tremor: Y Rigidity: Y Bradykinesia: Y Postural Instability: Y Decreased Arm Swing: Y Hypomimia: Y Micrographia: Y Sialorrhea: Y	Constipation: Y (w Colchicine, BNO 4/days) Dysfunctional sleep: Y Depression: Y	Part I = 8 Part II = 7 Part III = 22 Part IV = 0 Total = 37	Pramipexole 1.5mg ER i qd Rasagiline 1mg i qd	Metronidazole 400mg i qd Vancomycin 250mg ii bd Rifaximin 500mg i bd	Tremor: Improved Rigidity: Improved Bradykinesia: Y Postural Instability: Improved Decreased Arm Swing: Improved Hypomimia: Improved Micrographia: Improved Sialorrhea: Improved	Constipation: N (w Colchicine, BO 1/day) Dysfunctional sleep: Improved Depression: Improved	Part I = 7 Part II = 4 Part III = 15 Part IV = 0 Total = 26

Table: Table 1. Two cases with Parkinson’s Disease and Chronic Constipation who were treated with Antibiotic Combination Therapy

PD: Parkinson’s Disease, MDS-UPDRS: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (ranging from normal=0 to most severe=272), w: With, w/o: Without, BNO: Bowels not open, BO: Bowels open, i: One ii: Two, mg: Milligram, qd: Once a day, bd: Twice a day, qid: Four times a day


Disclosures:
Rhys Collyer: Centre for Digestive Diseases – Employee.
Anoja Gunaratne: Centre for Digestive Diseases – Employee.
Annabel Clancy: Centre for Digestive Diseases – Employee.
Thomas Borody: Centre for Digestive Diseases – Advisory Committee/Board Member, Consultant, Employee, Grant/Research Support, Patent Holder, Stockholder/Ownership Interest (excluding diversified mutual funds).


Rhys Collyer, BSc, Anoja W. Gunaratne, PhD, MSc, Annabel K. Clancy, PhD, Thomas J. Borody, MD, PhD, DSc, FRACP, FACG. P2274 - Antibiotic Combination Therapy Improves Symptoms of Parkinson’s Disease in Individuals With Chronic Constipation, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.