Upcycling Rhizopus-derived arginine-rich protein as a future functional ingredient for gut microbiota modulation

• Rhizopus protein enriches arginine and reshapes gut microbiota composition. • Fungal proteins promote beneficial taxa like Bifidobacterium spp. • Arginine links alternative proteins to microbiota and host responses. • Rhizopus protein suppresses inflammation-associated bacterial taxa. • Fungal proteins support gut barrier integrity and microbial stability While alternative proteins from microbial and plant origins are gaining attention for health benefits and sustainability, the comparative impact of fungal-derived alternative proteins versus traditional plant proteins on the human gut microbiome remains poorly understood, particularly regarding their specific metabolic contributions. This study investigated the effects of soy protein (SP), yeast protein (YP), and Rhizopus oligosporus –derived protein (RP) on the human gut microbiota using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). By utilizing this dynamic longitudinal model, we provide the first evidence that microbial proteins exhibit distinct ecological advantages over plant-based counterparts. Results showed that SP and YP altered the Firmicutes / Bacteroidetes ratio, while RP maintained microbial balance. Notably, RP selectively enriched beneficial taxa, specifically Bifidobacterium pseudocatenulatum , while simultaneously suppressing opportunistic species. Venn diagram revealed a greater number of shared ASVs between YP and RP, suggesting a closer ecological interaction unique to microbial-derived sources. This finding indicates that YP and RP may possess greater potential than plant-based proteins in shaping human gut microbiota. Crucially, amino acid profiling uncovered that RP contained markedly higher arginine levels, which is identified here as a key driver contributing to its microbiota-modulating effects. These findings address the existing knowledge gap by highlighting the differential impacts of alternative protein sources, positioning fungal proteins as superior functional dietary components for supporting gut health. Ultimately, this study provides a scientific foundation for the development of next-generation synbiotics and precision nutrition strategies, suggesting that microbial-derived proteins can serve as potent modulators for managing gut dysbiosis and enhancing systemic health in the transition toward sustainable global food systems.