Effects of a Saccharomyces uvarum Cell-Based Preparation on Gut Microbial Ecology and Metabolic Activity in Adults Without Diagnosed Gastrointestinal Disease: A Randomized Placebo-Controlled Crossover Pilot Study

Background/Objectives: Yeast-based probiotic candidates are increasingly investigated as potential modulators of gut ecology, although evidence in healthy individuals remains limited. This randomized, single-blind, crossover study primarily evaluated the tolerability of ATECREM Serius containing Saccharomyces uvarum SERIUS strain (>1010 CFU/g) and explored its effect on human gut microbiota. Methods: Forty-four volunteers completed the crossover intervention consisting of 2 months of ATECREM Serius (TRT1) and 2 months of placebo (PLT1), separated by 2 weeks of wash-out. Fecal microbiota was profiled by 16S rRNA gene sequencing, while fecal and urinary volatile organic compounds (VOCs) were profiled by GC–MS. Fecal free amino acids (FAAs) were also measured. Results: ATECREM Serius was well tolerated, with no treatment-related adverse events. Differences were observed for three out of five α-diversity indices, while β-diversity differed between TRT1 and PLT1. The relative abundance and prevalence of Bifidobacteriaceae and Bacteroides were increased in TRT1, whereas Enterobacteriaceae and clostridia sensu stricto were limited compared to placebo. Fecal metabolomics indicated an enrichment of organic acids, particularly SCFAs, in TRT1, whereas propanoic acid was reduced in PLT1. Fecal tryptophan and histidine decreased in TRT1, and urinary metabolomics showed a clearer clustering between TRT0 and TRT1, including a significant decrease of 2,5-dimethylfuran. Conclusions: In adults, ATECREM Serius was well tolerated within the investigated population and intervention period. Secondary exploratory analyses identified treatment-associated differences in selected gut microbial taxa and metabolomic features, including the increase in Bifidobacterium abundance compared to placebo. These findings are hypothesis-generating and require confirmation in larger, adequately powered studies.