The Effect of Synbiotics on the Upper Respiratory Tract Infection

Study Overview
=================
Brief Summary
-----------------
Gut microbiome manipulation to alter the gut-lung axis may potentially protect humans against respiratory infections. However, clinical trials of synbiotics, one of the microbiota-targeted intervention, in this regard is few. Therefore, this study aims to examine the effect of synbiotics on the incidence and severity of upper respiratory tract infection, gut microbiota composition and function, as well as biomarkers of immune function.

Official Title
-----------------
The Effect of Synbiotics on the Upper Respiratory Tract Infection in Healthy Subjects: A Randomized Double-Blind Trial

Conditions
-----------------
Upper Respiratory Tract Infection, Gut Microbiota, Immune Function

Intervention / Treatment
-----------------
* Dietary Supplement: Synbiotic
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: aged 18-65 years； good general health as determined by medical questionnaires; BMI <35 kg/m2; Exclusion Criteria: known congenital or acquired immune defects； allergies and other chronic or acute diseases requiring treatment； subjects with chronic gastrointestinal diseases; alcohol or drug misuse or both； pregnancy or lactation； vaccination against influenza within the last 12 months； use of oral antibiotics, probiotics, prebiotics, synbiotics, drugs active on gastrointestinal motility, or a laxative of any class within the last month.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>1.5 g maltodextrin in a sachet once daily for 8 weeks. | Dietary Supplement: Placebo<br>* Maltodextrin<br>|
| Experimental: Synbiotic<br>1.5 g synbiotics supplement of Lactobacillus rhamnosus HN001 (1.5×10^11 CFU) , Bifidobacterium lactis HN019 (7.5×10^10 CFU), and 500mg fructooligosaccharides in a sachet once daily for 8 weeks. | Dietary Supplement: Synbiotic<br>* Synbiotics sachet mainly contained Lactobacillus rhamnosus HN001, Bifidobacterium lactis HN019, and fructooligosaccharides.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of the upper respiratory tract infection |  | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of the upper respiratory tract infection |  | Up to 8 weeks | 
| The severity of the upper respiratory tract infection | The severity of the upper respiratory tract infection was assessed using the 24-item Wisconsin Upper Respiratory Symptom Survey (WURSS-24). Paricipants were required to answer the question, Did you have any symptom of upper respiratory tract infection today? If someone answered yes, he/she was instructed to complete WURSS-24 surveys daily. | Up to 8 weeks | 
| Changes in the gut mictobiota | Changes in the composition, diversity, and function of gut mictobiota in feces will be measured by 16S rRNA gene sequencing. | Baseline, 4 weeks, 8 weeks | 
| Changes in the levels of sIgA in saliva and feces |  | Baseline, 4 weeks, 8 weeks | 
| Changes in the levels of inflammatory cytokine | Changes in the levels of fasting plasma inflammatory cytokine, including CRP, IL-1β, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. | Baseline, 4 weeks, 8 weeks | 
| Changes in the number of T, B, NK and monocytes populations | Changes in the number of T-lymphocytes(CD45+CD3+), B-lymphocytes(CD45+CD19+), monocytes(CD45+CD14+), and natural killer cells(CD45+CD56+) in blood samples were evaluated by flow cytometer. | Baseline, 4 weeks, 8 weeks | 
| Changes in the subpopulation frequencies of blood lymphocyte and dendritic cells | Changes in the subpopulation of blood lymphocytes (the levels of CD3+, CD4+, CD8+, and CD25+) and dendritic cells (the levels of CD3-CD19-CD56-HLA-DR+ CD11c+cells and CD3-CD19-CD56-HLA-DR+CD123+ cells ) in blood samples were evaluated by flow cytometer. | Baseline, 4 weeks, 8 weeks | 
| Change in body weight |  | Baseline, 4 weeks, 8 weeks | 
| Change in BMI |  | Baseline, 4 weeks, 8 weeks | 
| Change in body fat composition |  | Baseline, 4 weeks, 8 weeks | 
| Change in the levels fasting plasma glucose |  | Baseline, 4 weeks, 8 weeks | 
| Changes in the levels of fasting plasma TC, TG, LDL, and HDL |  | Baseline, 4 weeks, 8 weeks |