Document Type : Original Article
Authors
1 Ward of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
2 Department of Neurology, Hazrat Rasool Medical Complex, Iran University of Medical Sciences, Tehran, Iran
3 Higher Education College of Health Sciences, Education Centre of Australia, Parramatta, NSW, Australia School of Human Nutrition, Macdonald Campus of McGill University, Quebec, Canada
Abstract
Background: Constipation is a common non-motor symptom (NMS) in Parkinson’s disease (PD), affecting up to 70% of patients and reducing quality of life (QOL). Probiotics may improve bowel function via gut microbiota modulation and gut-brain axis regulation. This randomized, double-blind, placebo-controlled trial evaluated the efficacy of six-week multi-strain probiotic supplementation on constipation in Iranian patients with PD.
Methods: Seventy-two patients with PD (aged 50-80 years, functional constipation per Rome IV criteria) were randomized 1:1 to probiotics or placebo. The probiotic capsule contained Lactobacillus acidophilus (L. acidophilus), Lactobacillus casei (L. casei), Lactobacillus rhamnosus (L. rhamnosus), Bifidobacterium lactis (B. lactis), Bifidobacterium longum (B. longum), and Bifidobacterium breve (B. breve) [1 × 10⁹ colony-forming unit (CFU) each, total 12 × 10⁹ CFU/day]. Dietary intake and physical activity were assessed and included as covariates in analysis of covariance (ANCOVA) models. Primary outcome was weekly spontaneous bowel movements (SBMs); secondary outcomes included Patient Assessment of Constipation-Quality of Life (PAC-QOL) and Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Baseline demographic, clinical, dietary, and physical activity characteristics were comparable between groups.
Results: The probiotic group showed a mean SBM increase of 3.41 versus 0.44 in placebo [between-group difference = 2.97, 95% confidence interval (CI): 2.46-3.53, P < 0.001]. PAC-QOL improved significantly (adjusted mean difference = -15.22, 95% CI: -22.32 to -8.11, P < 0.001). No significant changes were observed in UPDRS Part III.
Conclusion: Six-week probiotic supplementation increased bowel movement frequency and improved constipation-related QOL in patients with PD, with good tolerability. Larger, multicenter trials are warranted to confirm efficacy and explore potential effects on systemic PD progression.
Keywords
Main Subjects
- Luo Y, Qiao L, Li M, Wen X, Zhang W, Li X. Global, regional, national epidemiology and trends of parkinson's disease from 1990 to 2021: findings from the global burden of disease study 2021. Front Aging Neurosci 2024; 16: 1498756.
- Sarmadi M, Rezaei M, Poursadeghiyan M, Soltaninejad M, Moradi S, Ahangarzadeh M, et al. Burden of parkinson's disease in Iran: disparities, trends, and the impact of social development indicators. Neurol Sci 2025; 46(8): 3651-62.
- Di Biase L, Pecoraro PM, Di Lazzaro V. Validating the accuracy of parkinson's disease clinical diagnosis: A UK brain bank case-control study. Ann Neurol 2025; 97(6): 1110-21.
- Yao L, Liang W, Chen J, Wang Q, Huang X. Constipation in parkinson's disease: A systematic review and meta-analysis. Eur Neurol 2023; 86(1): 34-44.
- Ivan IF, Irincu VL, Diaconu Ș, Falup-Pecurariu O, Ciopleiaș B, Falup-Pecurariu C. Gastro-intestinal dysfunctions in Parkinson's disease (Review). Exp Ther Med 2021; 22(4): 1083.
- Shin C, Kim SI, Park SH, Kim JM, Lee JY, Chung SJ, et al. Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson's disease. NPJ Parkinsons Dis 2024; 10(1): 155.
- Zhai J, Zhang Y, Ma S, Zhang Y, Jin M, Yan H, et al. The role of gut microbiota dysbiosis in drug-induced brain injury: mechanisms and therapeutic implications. Front Cell Dev Biol 2025; 13: 1604539.
- Tai YC, Liao PH, Leta V, Lin CH, Chaudhuri KR. Irritable bowel syndrome based on Rome IV diagnostic criteria associates with non-motor symptoms of Parkinson's disease. Parkinsonism Relat Disord 2023; 113: 105496.
- Gao A, Lv J, Su Y. The Inflammatory Mechanism of Parkinson's Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut-Brain Axis. Brain Sci 2025; 15(2): 159.
- Kalyanaraman B, Cheng G, Hardy M. Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and ROS/RNS: Relevance to Parkinson's disease and therapeutic implications. Redox Biol 2024; 71: 103092.
- Xiang S, Ji JL, Li S, Cao XP, Xu W, Tan L, et al. Efficacy and Safety of Probiotics for the Treatment of Alzheimer's Disease, Mild Cognitive Impairment, and Parkinson's Disease: A Systematic Review and Meta-Analysis. Front Aging Neurosci 2022; 14: 730036.
- Leshchyshyn IM, Markulan LY, Okhotska OI, Susak YM, Byk PL. Quality of life in patients with chronic slow-transit constipation according to the PAC-QOL scale one year after surgical treatment: comparison with preoperative data and reference values. Wiad Lek 2025; 78(4): 726-34.
- Clina JG, Sayer RD, Friedman JE, Chui TK, Mehta T, Rimmer JH, et al. Reliability and Validity of the International Physical Activity Questionnaire Adapted to Include Adults With Physical Disability. J Phys Act Health 2024; 21(2): 189-96.
- Nikjooy AP, Jafari HP, Saba MAMP, Ebrahimi NMP, Mirzaei RM. Patient Assessment of Constipation Quality of Life Questionnaire: Translation, Cultural Adaptation, Reliability, and Validity of the Persian Version. Iran J Med Sci 2018; 43(3): 261-8.
- Xie L, Chen D, Zhu X, Cheng C. Efficacy and safety of probiotics in Parkinson's constipation: A systematic review and meta-analysis. Front Pharmacol 2022; 13: 1007654.
- Ibrahim A, Ali RAR, Manaf MRA, Ahmad N, Tajurruddin FW, Qin WZ, et al. Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson's disease: A randomised controlled trial. PLoS One 2020; 15(12): e0244680.
- Barichella M, Pacchetti C, Bolliri C, Cassani E, Iorio L, Pusani C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT. Neurology 2016; 87(12): 1274-80.
- Yin S, Zhu F. Probiotics for constipation in Parkinson's: A systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol 2022; 12: 1038928.
- Zheng Y, Zhang Z, Tang P, Wu Y, Zhang A, Li D, et al. Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Front Immunol 2023; 14: 1143548.
- Nápoles-Medina AY, Aguilar-Uscanga BR, Nápoles-Medina BG, Brand-Rubalcava PA, Tejeda-Martínez AR, Flores-Soto ME. Bridging the gap: Unveiling the gut's influence on Parkinson's disease through probiotic interventions. Neurol Perspect 2025; 5(4): 100206.
- Bedarf JR, Romano S, Heinzmann SS, Duncan A, Traka MH, Ng D, et al. A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson's Disease. NPJ Parkinsons Dis 2025; 11(1): 66.
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