Patients with Parkinson’s disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood–brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.
Background: Differential abundance of gut microbiota has found to be associated with Alzheimer’s disease (AD). However, the relative abundance of gut microbiota between dementia and mild cognitive impairment (MCI) in AD is not well studied. Objective: We attempted to identify differentially enriched gut microbes and their metabolic pathways in AD patients with dementia comparing to AD patients with MCI. Methods: Fecal samples were collected at Shuang Ho Hospital, Taipei Medical University, Taiwan and analyzed by whole metagenomic sequencing technique. For normal controls without AD (NC), 16S rRNA sequencing was obtained from the Taiwan Microbiome Database. A total of 48 AD (38 dementia and 10 MCI defined by cognitive function scores) and 50 NC were included. Microbiome alpha and beta diversities were estimated. Differentially enriched microbes were identified with HAllA, MaAsLin, DESeq2, and LEfSe statistical modeling approaches. Results: We found significantly increased abundance of Firmicutes but decreased abundance of Bacteroidetes at phylum level in AD compared to NC. In AD patients, cognitive function scores were negatively associated with abundance of Blautia hydrogenotrophica (Firmicutes), Anaerotruncus colihominis (Firmicutes), and Gordonibacter pamelaeae (Actinobacteria). In addition, microbial abundance in the sucrose and S-Adenosyl-L-methionine (SAMe) metabolic pathways were more enriched in MCI AD than dementia AD; and significantly associated with higher cognitive function scores. Conclusion: Gut microbe community diversity was similar in AD patients regardless of MCI or dementia status. However, differential analyses probed in lower-level taxa and metabolic pathways suggested that specific gut microbes in Firmicutes and Actinobacteria might involve in cognitive decline.
Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is the second leading cause of dementia after Alzheimer’s disease. Cognitive consequences after ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting the search for potential agents. The keyword “vascular dementia” was used to search ClinicalTrials.gov to determine agents represented in phases I, II, III, and IV. The agents were classified on the basis of their mechanisms. Of the 17 randomized controlled trials meeting our inclusion criteria, 9 were completed in the past 10 years, and 8 are ongoing or in the planning stages. We also identified one trial in phase I, nine in phase II, six in phase III, and one in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer’s dementia. Drug trials on vascular dementia overlap with drug trials targeting functional outcomes in cerebrovascular disease. International pharmaceutical companies’ investment in new drugs targeting VCI and vascular dementia remains insufficient.
Background: This study aims to determine whether periodontitis is a risk factor for transient ischemic attack (TIA) in young adults. Methods:The National Health Insurance (NHI) Research Database in Taiwan was the source of the data used in this retrospective cohort study. Individuals aged 20 to 53 years with periodontitis in 2001 and 2002 (n = 792,426) and an ageand sex-matched control group (n = 792,426) were selected. All participants were followed up until TIA diagnosis, 55 years of age, removal from the NHI program, death, or December 31, 2016. The incidence density and hazard ratio (HR) of newonset TIA were compared between individuals with periodontitis and controls.Periodontitis was defined by dentists according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 with concurrent antibiotic prescription or periodontal treatment excluding scaling performed by certified dentists. TIA was defined according to the ICD-9-CM code 435.x at hospital discharge. Results: After adjustment for confounding factors, the risk of developing TIA/minor ischemic stroke was calculated to be higher in participants with periodontitis (HR, 1.24; 95% confidence interval, 1.15-1.32; P <0.001) than in those without. The HR was slightly higher among people aged 20 to 40 years than among those aged 40 to 53 years. Conclusion: Periodontitis is associated with an increased risk of developing TIA/minor ischemic stroke. Periodontitis might be a modifiable risk factor for stroke in young adults. Clinicians must devote greater attention to this potential association to develop new preventive and therapeutic strategies for stroke in young adults.
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