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Advice to People with Parkinson's in My Clinic: Probiotics and Prebiotics

Hor JW, Toh TS, Lim SY, Tan AH

J Parkinsons Dis, 2024 Aug 23.
PMID: 39213091 DOI: 10.3233/JPD-240172

There is increasing evidence that microbial-based therapies can be useful in people with Parkinson's disease (PD). In this viewpoint, we provide a state-of-the-art review of the clinical and pre-clinical evidence for probiotics and prebiotics in PD. Currently, short-term clinical studies, including double-blind placebo-controlled randomized clinical trials, have demonstrated safety, and efficacy primarily in improving constipation-related symptoms. Pre-clinical studies consistently reported improvements in a range of biological markers and outcomes, including evidence for attenuation of gut dysfunction and neuroprotection. Bacteria from the genus Lactobacillus and Bifidobacterium have been the most frequently studied both in clinical and pre-clinical probiotics studies, while research into prebiotics is still limited and primarily involved resistant starch and fructooligosaccharides. We provide practical suggestions for clinicians on how to advise patients in the clinic regarding these popular treatments, and important caveats to be aware of. Finally, areas for further advancements are highlighted. It is envisaged that in the future, microbial-based therapies may benefit from personalization based on an enhanced understanding of a whole range of host factors and host-microbiome interactions.
Perioperative anaphylaxis: A five-year review in a tertiary paediatric hospital

Toh TS, Foo SY, Loh W, Chong KW, En Goh A, Hee HI, et al.

Anaesth Intensive Care, 2021 Jan;49(1):44-51.
PMID: 33472385 DOI: 10.1177/0310057X20964470

Making a diagnosis of perioperative anaphylaxis and identifying culprit drugs are diagnostic challenges. The aim of this study is to describe the perioperative presentation of anaphylaxis and results of patients who underwent allergy evaluation. This is a retrospective review of perioperative anaphylaxis of severity Grade 2 and above based on the Australian and New Zealand Anaesthetic Allergy Group criteria from 2015 to 2019 in a tertiary paediatric hospital. Data collected were demographics, clinical features, investigations and management. Of the 35,361 cases of paediatric anaesthesia, there were 15 cases of perioperative anaphylaxis, giving an incidence of four in 10,000. The median age was seven years (interquartile range four-15 years) with a male predominance of 86.7% (13/15). The severity of anaphylaxis was Grade 2 in 33.3% (5/15) and Grade 3 in 66.7% (10/15). The commonest presenting feature was hypotension (13/15, 86.7%) while the earliest symptom was respiratory change (9/15, 60.0%). Dynamic tryptase was raised in 75% (6/8) of the patients with adequate tryptase samples. Eight patients (53.3%) completed allergy testing, of whom five patients (62.5%) had IgE-mediated anaphylaxis with skin test positive to cefazolin (n = 3), atracurium (n = 1) and rocuronium (n = 1). Three patients (25.0%) had non-IgE-mediated reactions with negative skin tests. Although only half the patients completed allergy evaluation, a culprit drug could be identified in 62.5%, with antibiotics being the commonest. This emphasises the need for appropriate evaluation in cases of suspected perioperative anaphylaxis.
Gut microbiome in Parkinson's disease: New insights from meta-analysis

Toh TS, Chong CW, Lim SY, Bowman J, Cirstea M, Lin CH, et al.

Parkinsonism Relat Disord, 2022 Jan;94:1-9.
PMID: 34844021 DOI: 10.1016/j.parkreldis.2021.11.017

BACKGROUND: Gut microbiome alterations have been reported in Parkinson's disease (PD), but with heterogenous findings, likely due to differences in study methodology and population. We investigated the main microbiome alterations in PD, their correlations with disease severity, and the impact of study and geographical differences.
METHODS: After systematic screening, raw 16S rRNA gene sequences were obtained from ten case-control studies totaling 1703 subjects (969 PD, 734 non-PD controls; seven predominantly Caucasian and three predominantly non-Caucasian cohorts). Quality-filtered gene sequences were analyzed using a phylogenetic placement approach, which precludes the need for the sequences to be sourced from similar regions in the 16S rRNA gene, thus allowing a direct comparison between studies. Differences in microbiome composition and correlations with clinical variables were analyzed using multivariate statistics.
RESULTS: Study and geography accounted for the largest variations in gut microbiome composition. Microbiome composition was more similar for subjects from the same study than those from different studies with the same disease status. Microbiome composition significantly differed between Caucasian and non-Caucasian populations. After accounting for study differences, microbiome composition was significantly different in PD vs. controls (albeit with a marginal effect size), with several distinctive features including increased abundances of Megasphaera and Akkermansia, and reduced Roseburia. Several bacterial genera correlated with PD motor severity, motor response complications and cognitive function.
CONCLUSION: Consistent microbial features in PD merit further investigation. The large variations in microbiome findings of PD patients underscore the need for greater harmonization of future research, and personalized approaches in designing microbial-directed therapeutics.
Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry

Lim JL, Ng EY, Lim SY, Tan AH, Abdul-Aziz Z, Ibrahim KA, et al.

Neurol Sci, 2021 Oct;42(10):4203-4207.
PMID: 33559030 DOI: 10.1007/s10072-021-05056-x

BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry.
METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.
RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.
CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.
Genetic study of early-onset Parkinson's disease in the Malaysian population

Tay YW, Tan AH, Lim JL, Lohmann K, Ibrahim KA, Abdul Aziz Z, et al.

Parkinsonism Relat Disord, 2023 Jun;111:105399.
PMID: 37209484 DOI: 10.1016/j.parkreldis.2023.105399

BACKGROUND: About 5-10% of Parkinson's disease (PD) cases are early onset (EOPD), with several genes implicated, including GBA1, PRKN, PINK1, and SNCA. The spectrum and frequency of mutations vary across populations and globally diverse studies are crucial to comprehensively understand the genetic architecture of PD. The ancestral diversity of Southeast Asians offers opportunities to uncover a rich PD genetics landscape, and identify common regional mutations and new pathogenic variants.
OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort.
METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA).
RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes.
CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.
Fulltext Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry

Lim SY, Tan AH, Foo JN, Tan YJ, Chew EG, Annuar AA, et al.

J Mov Disord, 2024 Apr;17(2):213-217.
PMID: 38291878 DOI: 10.14802/jmd.24009

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.
Exercise Habits in People with Parkinson's: A Multinational Survey

Jagota P, Phutrakool P, Kamble N, Dang THT, Aldaajani Z, Hatano T, et al.

Mov Disord Clin Pract, 2024 Aug 29.
PMID: 39206964 DOI: 10.1002/mdc3.14197

BACKGROUND: Exercise has been demonstrated to result in improvements in physical function, cognition, and quality of life in People with Parkinson's (PwP) but its adoption is variable.
OBJECTIVES: To investigate exercise preferences, levels, influencing factors among a diverse Parkinson's disease (PD) population, to understand exercise adoption patterns and plan informed interventions.
METHODS: A cross-sectional survey collected data through online platforms and paper-based methods. The Exercise Index (ExI) calculated exercise level based on frequency and duration.
RESULTS: Of 2976 PwP, 40.6% exercised regularly, 38.3% occasionally, and 21.2% did not exercise. The overall mean ExI was 18.99 ± 12.37. Factors associated with high exercise levels included exercising in groups (ExI 24-26), weightlifting (ExI 27 (highest)), using muscle-building equipment (ExI 25-26), and exercising at home following an app (ExI 26). A positive trend between ExI and varied exercise groups, locations, types, and equipment was observed. No expected benefit from exercise achieved the lowest ExI (8). Having at least two exercise-promoting factors, a bachelor's degree or higher, receiving exercise advice at initial visits, and aged ≤40 years at PD onset were strong predictors of exercise (adjust OR = 7.814; 6.981; 4.170; 3.565). Falls and "other" most troublesome PD symptoms were negative predictors (aOR = 0.359; 0.466). Barriers to exercise did not predict the odds of exercise.
CONCLUSIONS: The study shows that PwP's exercise behavior is influenced by their exercise belief, age at PD onset, doctor's advice at initial visits, education level, symptoms, and exercise-promoting factors. High exercise levels were associated with certain types of exercises and exercising in groups.