Timeline
depression, PCOS
For this purpose, potential participants have a screening visit, where participants give written informed consent, blood and urine samples are collected and extensive patient history as well as questionnaires on PCOS symptoms, probiotic intake, depression symptoms and diet are collected. A soy challenge test as well as a functional gut permeability test are scheduled at home, requiring the participants to take urine and stool samples. For the soy challenge test, participants consume 2 × 250 ml soy drinks for two consecutive days, followed by urine sample collection at home each morning the day after soy consumption, similar to Setchell et al. [At the first visit (taking place four weeks at the latest after the screening visit), participants deliver the collected stool and urine samples and receive a randomized package of intervention product, which they will take for the next six months. The probiotic and placebo arms get 200 sachets each respectively, to be taken once daily. The metformin group receives 400 tablets of 500 mg metformin, to be taken once daily for the first 7 days of intervention before increasing the dosage to twice daily.Participants are asked to document any significant health changes or dietary intakes as well as the first day of each menstrual cycle. The intervention is scheduled to last 161 to 180 consecutive days, depending on the date of the second visit.At the end of their intervention, they will repeat the isoflavone challenge and the functional gut permeability tests at home and deliver the respective samples to the outpatient clinic at their second visit (taking place 24–26 weeks after the first visit). There, the blood and urine tests from the screening visit will be repeated.Participants in the blinded arms of the trial have the option to further take part in a follow-up period of an additional six months, during which they would take the probiotic formula (without placebo), followed by a follow-up visit scheduled one year after trial enrollment.In addition, two gastro-/sigmoidoscopies each will be performed at the beginning and the end of the intervention period in 30 voluntary participants (10 from each treatment arm planned) in order to obtain biopsy samples from the stomach, duodenum and sigmoid colon. These samples are used for the assessment of the mucosal gut microbiome as opposed to the luminal gut microbiome composition in stool samples. An overview of the timeline and visit schedule is provided in Table 
Overview of number of visits and outcome assessmentsWeeks+/- 3 or more days(-4)-(-1)(+/-3 days)-1(+/-3 days)0(+/-3 days)24–26(+/-3 days)26(+/-3 days)52(+/-3 days)