An exploratory analysis of the Phase 3 ECOSPOR III trial examines the effect of higher dosing of the oral microbiome therapeutic VOWST on the gastrointestinal microbiome.[1][2] Higher doses of VOWST improved pharmacokinetics, increased engraftment of microbial species, and altered clostridia microbiome and metabolite profiles.[1] This preparation consists of a purified suspension of Firmicutes bacterial spores obtained from qualified donors, containing 1×10^6 to 3×10^7 colony-forming units of spores.[2] VOWST is administered orally as 4 capsules over 3 consecutive days following antibiotic treatment.[1] The ECOSPOR III study enrolled 182 patients with a history of at least two recurrent Clostridioides difficile infections in a randomized, placebo-controlled trial.[1] Of the 349 patients in the combined analysis of ECOSPOR III and IV, 221 (63.3%) reported treatment-emergent adverse events by week 24, predominantly mild to moderate gastrointestinal symptoms such as gas, bloating, abdominal pain, fatigue, and diarrhea.[1] These microbiome changes may prevent recurrence of Clostridioides difficile infection.[1]