This study is a multicenter randomized double-blind placebo-controlled study. The research content is 1. The improvement effect of Bifidobacterium triple viable capsules（BIFICO） on motor symptoms and constipation and sleep in mild to moderate Parkinson's disease and the safety of the study; 2. the mechanism of the improvement effect of intestinal microecological changes on motor and constipation symptoms in mild to moderate Parkinson's disease.

This was a multicenter randomized double-blind placebo-controlled study that included 240 patients with primary PD with modified H-Y stage 1-3, randomly divided into treatment and placebo control groups; On the basis of the original PD medication, the treatment group was given bifidobacterium triple viable capsules (BIFICO) and the control group was given placebo; Patients who met the diagnosis of constipation were given Macrogol 4000 powder and /or Enema glycerine as a rescue medicine, and the observation period was 12+12 weeks.

All subjects underwent the World Movement Disorders Society Parkinson's Disease Comprehensive Rating Scale (MDS-UPDRS), Rome IV Constipation Diagnostic Scale, Cleveland Rating Scale, Parkinson's Disease Sleep Scale-2 (PDSS-2), and General Clinical Outcome Inventory (CGI) scores before and after treatment, and also recorded the patients' single bowel movement time and the use of Macrogol 4000 powder and Enema glycerine , to investigate the improvement effect of Bifido on motor symptoms and non-motor symptoms in PD patients. For the above patients, stool and blood samples were collected at the time of enrollment and at 12 weeks of observation.

At the same time,120 age-and gender-matched healthy adults without constipation were recruited, and their stool and blood samples were collected; the stool samples of PD patients before and after treatment and healthy controls were subjected to the determination of fecal flora 16S DNA abundance. Stool samples of 10 PD patients and 10 healthy controls were taken from each group for metagenomic sequencing. Detection of small molecule metabolites, PD-related genes in blood. To investigate the effect of BIFICO on levodopa pharmacokinetics, levodopa pharmacokinetic measurements will be performed at Friendship Hospital. For patients who agree to participate and sign the informed consent form, blood specimens will be collected consecutively at Visit 2 and Visit 11 after taking Levodopa and Benserazide Hydrochloride Tablets for levodopa blood concentration measurement.

Inclusion Criteria:

• Age 40-85 years old, both male and female;
• Patients with primary Parkinson's disease who meet the 2015 MDS clinical diagnostic criteria; PD with modified Hoehn-Yahr stage 1-3 and MDS-UPDRS II+III score ≥ 14 and no significant off periods or off periods ≤ 1.5 hours per day (excluding morning motor inability);
• Pre-enrollment therapeutic medications included Levodopa complex preparation, and all Parkinson's disease medications were unadjusted and motor symptoms were stable for 28 days prior to enrollment;
• No probiotic or/and prebiotic (including lactulose) and antibiotic therapy for 60 days prior to enrollment, and if so, a 60-day washout period;
• Understand and agree to follow the study protocol, agree to be enrolled and sign the informed consent form.

Exclusion Criteria:

• Parkinson's superimposed syndrome and secondary Parkinson's syndrome, such as multiple system atrophy, progressive supranuclear palsy, etc.；
• Taking any probiotic or prebiotic (including lactulose) within 60 days prior to enrollment; having inflammation at any site and using any antibiotic within 60 days prior to enrollment; or having blood leukocytes above the upper limit of normal at screening；
• Combined endocrine disorders, such as history of diabetes or fasting glucose ≥ 7.8 mmol/L;
• Comorbid other neurological disorders, such as cognitive impairment, Mini-Mental State Examination （MMSE） scale score <24; severe anxiety states and/or severe depressive states (Hamilton Depression Inventory-17 item score >17, Hamilton Anxiety Scale score ≥14, or being treated with antidepressant anxiety medication); Note: Those who were taking antidepressant and anxiety drugs and had no adjustment in the last 28 days, and whose score of Hamilton Depression Scale -17 was less than 17, and Hamilton Anxiety Scale score was less than 14 were not included in the exclusion criteria; Severe autonomic nervous disease occurs within 5 years of onset, malignancy, spinal cord lesions, epilepsy, autonomic disorders (urinary retention, urinary incontinence, or upright hypotension , blood pressure drop ≥30/15 mmHg at any time point within 5 minutes of uprightness), etc.; new cerebrovascular disease or sequelae of severe cerebrovascular disease within 6 months, which affects the assessment；
• Gastrointestinal tumors, history of inflammatory bowel disease, other acute and chronic inflammation of the gastrointestinal tract (including acute attacks of cholecystitis) within 3 months；
• History of gastrointestinal surgery (excluding endoscopic resection of gastrointestinal benign polyps, appendicitis resection) or constipation caused by surgery；
• History of anal fissure, perianal abscess, irreversible anal prolapse, pelvic trauma；
• Severe cardiovascular disease (such as congestive heart failure with a heart function classification of Ⅲ-Ⅳ by the American Heart Association, a history of myocardial infarction within 6 months, etc.);
• Severe liver and kidney dysfunction with glutamate-pyruvate transaminase, aspartate transaminase and total bilirubin 2.0 times higher than the upper limit of normal; serum creatinine 2.0 times higher than the upper limit of normal;
• Pregnant and lactating women or women of childbearing age (40-60 years) who are human chorionic gonadotropin (HCG)-positive;
• Known allergy to test drugs or related products;
• People with a history of drug abuse or alcohol dependence;
• Those who have participated in other clinical trials within 3 months prior to enrollment;
• Refusal to enroll and inability to cooperate with the investigator; patients judged by the investigator to be unsuitable for enrollment.

Study is double blind design