METHODS: In this double-blind, randomized, placebo-controlled, single-center trial, 280 patients with PD were screened, and 72 eligible patients were block-randomized (1:1) to receive either multistrain probiotics capsules (n = 34) or identical-appearing placebo (n = 38), for 4 weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last 2 weeks of intervention compared with the 2-week preintervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome.
RESULTS: SBM increased by 1.0 ± 1.2 per week after treatment with probiotics and decreased by 0.3 ± 1.0 per week in the placebo group (mean difference 1.3, 95% confidence interval 0.8-1.8, p < 0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency (p = 0.009) and quality of life related to constipation (p = 0.001). In the treatment group, 65.6% reported satisfaction with the intervention vs only 21.6% in the placebo group (p < 0.001). One patient (2.9%) in the treatment group withdrew due to a nonserious adverse event. Fecal calprotectin did not change significantly during the study.
CONCLUSIONS: Multistrain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action.
CLINICALTRIALSGOV IDENTIFIER: NCT03377322.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for people with PD, multistrain probiotics significantly increased the average number of SBM per week.
METHODS: A total of 163 patients were randomized into two groups: Group A to consume 350 mL of sterilized probiotic with 5.85 g polydextrose daily for 1 week and Group B without polydextrose. Intestinal transit time, fecal pH, fecal weight, and modified Garrigues questionnaires for pre- and post-consumption were assessed.
RESULTS: Median intestinal transit time was significantly reduced from 58 (IQR 43-72) to 45 (IQR 24-59) hours and 48 (IQR 31-72) to 30 (IQR 24-49) hours for Groups A and B, respectively (p
METHODS: Patients referred to the Endoscopic Unit for colonoscopy were recruited for the study. Stool samples were collected prior to bowel preparation, and tested for occult blood with both gFOBT and FIT. Dietary restriction was not imposed. To assess the validity of either tests or in combination to detect a neoplasm or cancer in the colon, their false positive rates, their sensitivity (true positive rate) and the specificity (true negative rate) were analyzed and compared.
RESULTS: One hundred and three patients were analysed. The sensitivity for picking up any neoplasia was 53% for FIT, 40% for gFOBT and 23.3% for the combination. The sensitivities for picking up only carcinoma were 77.8% , 66.7% and 55.5%, respectively. The specificity for excluding any neoplasia was 91.7% for FIT, 74% for gFOBT and 94.5% for a combination, whereas for excluding only carcinomas they were 84%, 73.4% and 93.6%. Of the 69 with normal colonoscopic findings, FOBT was positive in 4.3%, 23.2 %and 2.9% for FIT, gFOBT, or combination of tests respectively.
CONCLUSION: FIT is the recommended method if we are to dispense with dietary restriction in our patients because of its relatively low-false positivity and better sensitivity and specificity rates.
METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.
RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.
INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.