Even after decades of research and pharmaceutical development, cancer is still one of the most common causes of death in the western population and the management of cancer will remain a major challenge of medical research. One of the most common types of cancer is colorectal cancer (CRC). Prevention by detection of early-stage precursors is the most reliable method to prevent CRC development. In dependence of age, familial predisposition, and other risk factors the preventative routine screening for CRC by colonoscopy should be performed at least twice in intervals of about ten years. Although colonoscopy is a life-saving clinical examination reducing both incidence and mortality of CRC significantly, it has still a bad reputation in the population as an uncomfortable procedure with unpleasant side effects lasting sometimes over days to weeks. These effects are most likely caused by the bowel preparation before colonoscopy, which is crucial for a successful colonoscopy with high quality. Beside pain, bleeding and other rare but severe complications of colonoscopy, cleaning of the intestinal mucosa alters the gut microbiome significantly and consistently. Abdominal pain, cramps, diarrhea, nausea, bloating, and constipation are common adverse events which can continue to affect patients for days or even weeks after the procedure. In this multicenter, placebo controlled, double blind clinical trial, we investigated the effect of an intervention with a multispecies probiotic formulation for 30 days on the adverse events due to bowel preparation. We show that the treatment of participants with the multispecies probiotic formulation decreases the number of days with constipation significantly, and reduced pain, bloating, diarrhea, and general discomfort. 16S based amplicon analyses reveal recovery of administered probiotic strains from stool samples and differences in alpha diversity dynamics with higher variability in the probiotic group compared to the placebo group. In conclusion, the probiotic ameliorates the side effects after colonoscopy and might be an important supplement to increase acceptance of this life-saving preventative examination. Further, we present here for the first time that probiotic intervention of only 30 days affects alpha diversity parameters in stool samples.