Clinical trial NCT05628987: The Association of Gut Microbiota and Spermatogenic Dysfunction
Official title: The Association of Gut Microbiota and Spermatogenic Dysfunction
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Infertility, Male
Azoospermia
Oligozoospermia
Asthenozoospermia
Teratozoospermia
Keywords: Microbiota
Infertility, Male
Sperm
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2022-11-29
Enrollment: 306
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy volunteers and patients will be recruited from the outpatient clinics of the Department of Andrology, Reproduction in our participant hospitals. Patients are from licensed doctor of the clinical research center. The age of healthy volunteers and patients in the same hospital will be matched.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Microbiome
timeFrame: Baseline
measure: Metabolomics
timeFrame: Baseline
Secondary outcomes:
measure: Physical activity time
timeFrame: Baseline
measure: Daily sitting time
timeFrame: Baseline
measure: Eating habits
timeFrame: Baseline
measure: Sleeping time
timeFrame: Baseline
measure: Education level
timeFrame: Baseline
measure: Family income (CNY)
timeFrame: Baseline
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Baseline
measure: Years of smoking
timeFrame: Baseline
measure: Number of cigarettes smoked
timeFrame: Baseline
measure: History of drinking in the past one month
timeFrame: Baseline
measure: History of drinking in the past 7 days
timeFrame: Baseline
measure: Body Mass Index (BMI)
timeFrame: Baseline
measure: Waistline
timeFrame: Baseline
measure: Spermatic concentration
timeFrame: Baseline
measure: Total sperm count
timeFrame: Baseline
measure: Spermatic progressive motility
timeFrame: Baseline
measure: Percentage of normal morphology of sperm
timeFrame: Baseline
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial Fertility Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Second Provincial General Hospital
state: Guangdong
city: Guanzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
Study officials:
affiliation: Southern Medical University, China
name: Hongwei Zhou
role: STUDY_CHAIR
References:
citation: He Y, Wu W, Zheng HM, Li P, McDonald D, Sheng HF, Chen MX, Chen ZH, Ji GY, Zheng ZD, Mujagond P, Chen XJ, Rong ZH, Chen P, Lyu LY, Wang X, Wu CB, Yu N, Xu YJ, Yin J, Raes J, Knight R, Ma WJ, Zhou HW. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat Med. 2018 Oct;24(10):1532-1535. doi: 10.1038/s41591-018-0164-x. Epub 2018 Aug 27.
citation: Yang H, Zhang J, Xue Z, Zhao C, Lei L, Wen Y, Dong Y, Yang J, Zhang L. Potential Pathogenic Bacteria in Seminal Microbiota of Patients with Different Types of Dysspermatism. Sci Rep. 2020 Apr 23;10(1):6876. doi: 10.1038/s41598-020-63787-x.
citation: Ding N, Zhang X, Zhang XD, Jing J, Liu SS, Mu YP, Peng LL, Yan YJ, Xiao GM, Bi XY, Chen H, Li FH, Yao B, Zhao AZ. Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes. Gut. 2020 Sep;69(9):1608-1619. doi: 10.1136/gutjnl-2019-319127. Epub 2020 Jan 2.
citation: Martinot E, Thirouard L, Holota H, Monrose M, Garcia M, Beaudoin C, Volle DH. Intestinal microbiota defines the GUT-TESTIS axis. Gut. 2022 Apr;71(4):844-845. doi: 10.1136/gutjnl-2021-324690. Epub 2021 May 13. No abstract available.