The study evaluated yeast protein (YP) as a sustainable alternative protein for supporting gut health in older adults by examining its effects on the gut microbiota, microbial metabolites, intestinal barrier function, and inflammation. Using the SIFR® model with fecal microbiota from six men aged 50–65 years, YP was compared with whey protein isolate (WPI) and soy protein isolate (SPI) at a dose equivalent to 40 g/day. Yeast protein increased the production of beneficial short-chain fatty acids (SCFAs), particularly butyrate-associated metabolites, promoted microbial diversity, and helped restore several butyrate-producing bacteria, including Faecalibacterium prausnitzii, Anaerostipes hadrus, Roseburia hominis, and Dysosmobacter welbionis. In the intestinal cell model, fermented YP samples produced the strongest improvement in transepithelial electrical resistance (TEER) among the tested proteins, indicating better epithelial barrier integrity, while increasing the anti-inflammatory cytokine IL-10 and reducing TNF-α, IL-1β, and CXCL10. YP also generated 27% less gas than WPI and 19% less than SPI, suggesting potentially better gastrointestinal tolerability, and produced the lowest levels of TMAO among the protein sources. Overall yeast protein can beneficially shape the gut microbiota and its metabolite profile, strengthen intestinal barrier function, and reduce inflammatory responses.
