An increasing number of studies have provided evidence for the hypothesis that the pathogenesis of Parkinson’s disease (PD) may derive from the gut. Firstly, Lewy pathology can be induced in the enteric nervous system (ENS) and be transported to the central nervous system (CNS) via the vagal nerve. Secondly, the altered composition of gut microbiota causes an imbalance between beneficial and deleterious microbial metabolites which interacts with the increased gut permeability and the gut inflammation as well as the systemic inflammation. The activated inflammatory status then affects the CNS and promotes the pathology of PD. Given the above-mentioned findings, researchers start to pay attention to the connection between PD and gastrointestinal diseases including irritable bowel syndrome, inflammatory bowel disease (IBD), microscopic colitis (MC), gastrointestinal infections, gastrointestinal neoplasms, and colonic diverticular disease (CDD). This review focuses on the association between PD and gastrointestinal diseases as well as the pathogenesis of PD from the gut.

Objective: Parkinson’s disease (PD) is possibly caused by genetic factors, environmental factors, and gut microbiota dysbiosis. This study aims to explore whether the microbiota contributes to the behavior abnormalities of PD.Methods: We transplanted gut microbiota from patients with PD or healthy controls (HC) into microbiota-free honeybees. We also established two more groups, namely the rotenone (ROT) group, in which PD-like symptoms of honeybees were induced by rotenone, and the conventional (CV) group, in which honeybees were colonized with conventional gut microbiota. The climbing assay was performed to assess the motor capabilities of honeybees. Histopathological examination was conducted to evaluate the integrity of gut mucosa. Tyrosine hydroxylase (TH) gene expression levels and dopamine (DA) concentrations in the brain were also examined. Additionally, metagenomics and full-length 16S rRNA analyses were performed to identify alterations in gut microbiota profiles, both in PD patients and honeybees.Results: Honeybees in the PD and ROT groups exhibited slower climbing speeds, downregulated TH gene expression, and impaired gut barriers. Both the HC and PD groups of honeybees successfully harbored a portion of gut microbiota from corresponding human donors, and differences in microbial composition were identified. Morganella morganii and Erysipelatoclostridium ramosum exhibited significantly increased relative abundance in the HC group, while Dorea longicatena, Collinsella aerofaciens, Lactococcus garvieae, Holdemanella biformis, Gemmiger formicilis, and Blautia obeum showed significantly increased relative abundance in the PD group. Functional predictions of microbial communities in the PD group indicated an increased synthesis of hydrogen sulfide and methane.Conclusion: A novel PD model was induced in honeybees with rotenone and gut microbiota from PD patients. This study linked PD-related behaviors to altered gut microbiota, highlighting a potential gut microbiota-brain axis involvement in PD pathogenesis. We identify previously unrecognized associations of Dorea longicatena, Collinsella aerofaciens, Lactococcus garvieae, Holdemanella biformis, Gemmiger formicilis, and Blautia obeum with PD. Additionally, pathways related to hydrogen sulfide and methane synthesis have been previously suggested as potential contributors to the development of PD, and our research further supports this hypothesis.

Background: The number of patients with Alzheimer’s disease (AD) worldwide is increasing yearly, but the existing treatment methods have poor efficacy. Transcranial alternating current stimulation (tACS) is a new treatment for AD, but the offline effect of tACS is insufficient. To prolong the offline effect, we designed to combine tACS with sound stimulation to maintain the long-term post-effect.Materials and methods: To explore the safety and effectiveness of tACS combined with sound stimulation and its impact on the cognition of AD patients. This trial will recruit 87 patients with mild to moderate AD. All patients were randomly divided into three groups. The change in Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) scores from the day before treatment to the end of treatment and 3 months after treatment was used as the main evaluation index. We will also explore the changes in the brain structural network, functional network, and metabolic network of AD patients in each group after treatment.Discussion: We hope to conclude that tACS combined with sound stimulation is safe and tolerable in 87 patients with mild to moderate AD under three standardized treatment regimens. Compared with tACS alone or sound alone, the combination group had a significant long-term effect on cognitive improvement. To screen out a better treatment plan for AD patients. tACS combined with sound stimulation is a previously unexplored, non-invasive joint intervention to improve patients’ cognitive status. This study may also identify the potential mechanism of tACS combined with sound stimulation in treating mild to moderate AD patients.Clinical Trial Registration: Clinicaltrials.gov, NCT05251649. Registered on February 22, 2022.