This study aims to investigate whether Sporoderm-removed Ganoderma lucidum spore powder (RGLS) ameliorates depression in thyroid cancer patients through gut-brain axis modulation, and to elucidate the underlying microbial and metabolic mechanisms. This 3-month randomized, double-blind, placebo-controlled trial will enroll 300 postoperative papillary thyroid carcinoma patients with depressive symptoms (HAMD-24 ≥ 8). Participants will be randomly assigned(2 : 1) to receive RGLS (4 g/day) or matched placebo.

Inclusion Criteria:

• Outpatients at Zhejiang Cancer Hospital with histologically confirmed papillary thyroid carcinoma (post-surgery) and depressive symptoms (HAMD-24 score ≥ 8, confirmed by a clinical psychologist).
• Han Chinese ethnicity.
• No history of depression or other psychiatric disorders.
• Age 18-80 years.
• Female.

Exclusion Criteria:

• Suffering from other gastrointestinal system diseases.
• History of gastrointestinal surgery prior to intervention.
• Including those with other concurrent malignancies requiring chemotherapy, radiotherapy, biological therapy, or traditional Chinese medicine treatment.
• Received antibiotic treatment or microecological modulators within 3 months prior to intervention.
• Acute intestinal obstruction.
• Patients who are currently taking antidepressant medication, or those whom the investigators judge require immediate initiation of antidepressant medication treatment.
• Organic brain diseases, brain trauma.
• History of psychiatric disorders, use of psychoactive substances (e.g., drugs).
• Severe liver or kidney dysfunction.
• Pregnancy or lactation.