The Association of Gut Microbiota and Spermatogenic Dysfunction

Sponsor

Zhujiang Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05628987

Collaborator

National Natural Science Foundation of China (Other)

306

Enrollment

Locations

Anticipated Duration (Months)

153

Patients Per Site

12.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicenter, case-control study that aims to investigate the relationship between microbiota and sperm quality via stool, blood, and urine microbiome, metabolomics, and collected clinical metadata. The results of the spermatogenic dysfunction, including aspermia, oligozoospermia, asthenozoospermia, and teratozoospermia, will be compared to normal basic semen analysis utilizing the World Health Organization (WHO) semen analysis procedure 5th edition.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Male Azoospermia Oligozoospermia Asthenozoospermia Teratozoospermia	Other: no intervention

Detailed Description

Infertility is a global issue that affects as much as 10%-15% of couples. Approximately half of infertility can be attributed to men. Recently, a worldwide accelerated decline in sperm counts was reported. And the gut microbiome modulates many physiological functions and diseases, including host immunity, metabolic diseases, neuropsychiatric disorders, and so on. Recent publications demonstrate the links between intestinal microbiota and sperm production in fat animals and a few patients. And systemic clinical research would be necessary to explore the human microbiota and males with fertility disorders.

The primary objective of the study is to determine the links between the gut microbiome and sperm quality utilizing microbiome and metabolomics. Stool, blood, and urine will be collected when a patient completes basic semen analysis and informed consent is signed. Microbiome and metabolomics will be compared among aspermia, oligozoospermia, asthenozoospermia, teratozoospermia, and normal individuals.

Study Design

Study Type:

Observational

Anticipated Enrollment :

306 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

The Association of Gut Microbiota and Spermatogenic Dysfunction

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Azoospermia After an abstinence period of 2-7 days, two basic semen analysis, the absence of spermatozoa	Other: no intervention Observational studies, no intervention
Oligozoospermia After an abstinence period of 2-7 days, the total sperm number <3910^6 per ejaculate or the sperm concentration < 15 10^6 per ml	Other: no intervention Observational studies, no intervention
Asthenozoospermia After an abstinence period of 2-7 days, the progressive motility (PR) < 32%	Other: no intervention Observational studies, no intervention
Teratozoospermia After an abstinence period of 2-7 days, the percentage of morphologically normal spermatozoa <4%	Other: no intervention Observational studies, no intervention
Control After an abstinence period of 2-7 days, the basic semen analysis is normal.	Other: no intervention Observational studies, no intervention

Outcome Measures

Primary Outcome Measures

Microbiome [Baseline]
The microbial composition of the stool samples was determined by 16S rRNA (ribosomal ribonucleic acid) gene sequencing analysis and metagenomics. Comparison of microbial abundance and diversity of healthy volunteers and patients with spermatogenic dysfunction.
Metabolomics [Baseline]
Metabolomics is the large-scale study of small molecules, such as fatty acids, bile acids, lipid mediators and others. Comparison of metabolites of healthy volunteers and patients with spermatogenic dysfunction.

Secondary Outcome Measures

Physical activity time [Baseline]
Analyzing physical activity (hours/week) of different groups. The questionnaire about Physical Activity Time, "Over the past 30 days, on average how many hours per week did you usually spend on physical activity?"
Daily sitting time [Baseline]
Analyzing daily sitting time (hours) of different groups. The questionnaire about Daily Sitting Time, "Over the past 7 days, on average how many hours did you usually spend sitting on a typical day?"
Eating habits [Baseline]
Analyzing eating habits (vegetarian or meat lover) of different groups.
Sleeping time [Baseline]
Analyzing daily sleeping time (hours) of different groups. The questionnaire about Sleeping Time, "Over the past 7 days, on average how many hours did you usually sleep per day?"
Education level [Baseline]
Analyzing education level (highest grade or level of school) of different groups. The questionnaire about Education Level, "What is the highest grade or level of school you have completed or the highest degree you have received? The response categories are: less than 9th grade education, 10-12th grade education (includes no diploma), some college or associates (AA) degree, and college graduate or higher."
Family income (CNY) [Baseline]
Analyzing annual family income (CNY) of different groups. The questionnaire about Family Income, "How much is annual family income (CNY)?"
Patient Health Questionnaire-9 (PHQ-9) [Baseline]
Analyzing Patient Health Questionnaire-9 (PHQ-9) scores of different groups. The Patient Health Questionnaire 9 (PHQ-9) is one of the tools used to screen for the presence and severity of depression. Each response category of 'not at all', 'several days', 'more than half the days' and 'nearly every day' is assigned a score of 0, 1, 2 and 3 respectively. The total score is calculated by adding together the scores for the 9 questions. The final scores of 0-4, 5-9, 10-14, 15-19, 20-27 are the ranges for none, mild, moderate, moderately severe and severe, respectively.
Years of smoking [Baseline]
Analyzing years of smoking of different groups. The questionnaire about Years of Smoking, "For about how many years have you smoked? 0 means non-smoker"
Number of cigarettes smoked [Baseline]
Analyzing number of cigarettes smoked of different groups. The questionnaire about Number of Cigarettes Smoked, "During the past 30 days, on average how many cigarettes did you smoke per day? non-smoker choose 0"
History of drinking in the past one month [Baseline]
Analyzing history of drinking of different groups in the past one month. "Considering all types of alcoholic beverages, during the past one month, do you have at least 1 drink of any kind of alcohol per week, not counting small tastes or sips? By a drink, I mean 500 ml beer, 50 ml liquor, or 500ml other type of alcoholic beverage."
History of drinking in the past 7 days [Baseline]
Analyzing history of drinking of different groups in the past 7 days. "Considering all types of alcoholic beverages, during the past 4 weeks, do you have at least 1 drink of any kind of alcohol, not counting small tastes or sips? By a drink, I mean 1000 ml beer, 200 ml liquor, or 1000ml other type of alcoholic beverage.""Considering all types of alcoholic beverages, during the past one month, do you have at least 1 drink of any kind of alcohol per week, not counting small tastes or sips? By a drink, I mean 500 ml beer, 50 ml liquor, or 500ml other type of alcoholic beverage."
Body Mass Index (BMI) [Baseline]
To analyze Body Mass Index (kg/m^2) of different groups, height(cm) and weight(kg) will be measured.
Waistline [Baseline]
Analyzing waistline (cm) of different groups.
Spermatic concentration [Baseline]
To analyze spermatic concentration (10^6 per ml). According to the World Health Organization (WHO) semen analysis procedure 5th edition, spermatic concentration will be measured.
Total sperm count [Baseline]
To analyze total sperm count (10^6 per ejaculate). According to the World Health Organization (WHO) semen analysis procedure 5th edition, total sperm count will be measured.
Spermatic progressive motility [Baseline]
To analyze spermatic progressive motility (%). According to the World Health Organization (WHO) semen analysis procedure 5th edition, progressive motility will be measured.
Percentage of normal morphology of sperm [Baseline]
To analyze percentage of normal morphology of sperm (%). According to the World Health Organization (WHO) semen analysis procedure 5th edition, percentage of normal morphology of sperm will be measured.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Aged 18 to 45 years, males
Body Mass Index (BMI):18.5-29.9 kg/m^2
After an abstinence period of 2-7 days, two abnormal semen analysis, the absence of spermatozoa from both replicates will be included in the azoospermia group, the total sperm number (<39*10^{6 per ejaculate) or the sperm concentration ( < 15 * 10}6 per ml) will be oligozoospermia group, the progressive motility (PR) (< 32%) will be asthenozoospermia group; the percentage of morphologically normal spermatozoa (<4%) will be teratozoospermia group
Willing to provide feces, urine, blood samples, able to complete study questionnaires aimed at lifestyle factors (cigarette smoking, high temperature environment and others ) and other data collection instruments (e.g. physical activity, food frequency questionnaire, stress and others)

Exclusion Criteria:

Age < 18 or > 45 years
History of Zocanidin, Vitamin E, antibiotics, clyster, gastrointestinal endoscope in the past 30 days, or other drugs known to interact with semen quality or gut microbiota, history of high alcohol consumption (liquor over 200 ml, beer over 1000 ml) in the past 7 days or drinking every week in the past month
A known genetic cause of male factor spermatogenesis dysfunction, including chromosomal or gene disorders (e.g. Y chromosome deletions, CFTR mutation)
History of male reproductive system (e.g. testis, epididymis, seminiferous duct and others) damage, surgery, tumor or infection
History of Crohn's disease, ulcerative colitis, acute gastrointestinal disease, renal failure, liver cirrhosis, hypoplasia, X-rays exposure and other diseases related to spermatogenic dysfunction, history of intestinal gastrointestinal surgery (exclude appendix surgery)
History of psychoses or other mental conditions that would result in cognitive impairment and inability to participate in any part of this study including the informed consent process