Fig. 1

Study design of the ProPCO-RCT study; First, the participants´ inclusion/exclusion criteria are determined with detailed patient histories, questionnaires and blood analysis at the screening visit. Then, 30 out of the total 180 participants voluntarily submit to an endoscopy in order to obtain gut biopsy samples for detailed microbiome analysis. Next, all participants perform a soy challenge test and a gut permeability test at home and collect stool and urine samples, which they return at visit (1) There they will be randomized into either the open-label metformin arm or the double-blinded probiotic-placebo arms, with the 30 endoscopy participants being allocated equally across the three groups. If they are randomized into the probiotic or placebo groups, they receive a randomized package containing the blinded trial substances. They then take the study medication for 6 months, before repeating both the endoscopies and the tests at home and returning for visit (2) There all assessments from the screening visit are repeated. Participants of the probiotic and placebo arms may prolong their participation by taking the probiotic product in a 6-months follow-up period, before returning for the final follow-up visit, which is identical to the visit 2; w endo: with a scheduled endoscopy visit; wo endo: without a scheduled endoscopy visit;