The goal of this clinical trial is to learn how the antifungal drug fluconazole affects the gut microbiome and immune system in healthy volunteers.

The main questions it aims to answer are:

• Does fluconazole change the gut bacteriome and mycobiome composition after 14 days of treatment?
• How long do these changes last (4 weeks and 6 months after treatment)?
• Does fluconazole affect the body's immune responses, such as blood cell activity and antifungal antibodies?

Researchers will compare two groups: participants who take fluconazole for 14 days and participants who receive no intervention.

Participants will:

• Either take one fluconazole tablet (200 mg) daily for 14 days, or receive no treatment
• Provide stool samples and blood samples at several timepoints
• Return for follow-up visits up to 6 months after treatment

This study is conducted at Amsterdam UMC, location AMC, with a planned enrollment of 50 healthy male volunteers aged 18-35 years.

Inclusion Criteria:

• Male, 18-35 years of age at the time of signing informed consent
• Healthy, as determined by medical history and physical examination; minor clinical abnormalities allowed if not introducing additional risk or interfering with study procedures
• Capable of giving written informed consent and able to comply with study requirements
• Normal defecation pattern (≤3 times/day and ≥3 times/week)

Exclusion Criteria:

• Major illness in the past 3 months, or significant chronic medical illness deemed unfavorable for enrollment
• Past or current gastrointestinal disease that may influence the gut microbiota (including inflammatory bowel disease or medication-treated irritable bowel syndrome)
• History of immunodeficiency
• History of malignancy
• Alcohol intake >3 units/day on average
• Known allergy to antifungal drugs
• Use of antibiotics (except topical) within the past 3 months
• Use of antifungals (except topical) within the past 3 months
• Planned prolonged travel (>4 weeks) to tropical countries during the study period
• Receipt of an investigational product within 3 months prior to study day 0
• Use of prescription or non-prescription drugs, herbal or dietary supplements within 3 months (unless deemed safe by investigator)
• Difficulty with blood donation or poor venous access in either arm
• Donation of >500 mL of blood in the past 3 months
• Any other condition or circumstance that, in the investigator's opinion, could be harmful to the subject or compromise data interpretation

Healthy males are eligible to participate.