Beyond protein source: The structure-gut microbiome axis in alternative protein digestion, fermentation, and health

Alternative proteins from plant, algal, fungal, and microbial sources are increasingly recognized for their potential to influence gut microbiota. However, the role of protein structure in shaping these interactions remains poorly understood. This review examines how key structural attributes of alternative proteins-including amino acid composition, folding characteristics, aggregation behavior, and enzymatic accessibility, govern gastrointestinal digestion. It also explores how these structural features affect microbial fermentation and the subsequent nutritional and functional outcomes. Structural variations influence peptide generation, microbial substrate utilization, and the production of metabolites such as short-chain fatty acids and proteolytic compounds. Current evidence indicates that protein conformation and digestibility, rather than source alone, are major determinants of microbiome responses. However, progress is hindered by limited multi-omics integration and a lack of standardized models and in-vivo validation. Collectively, current evidence supports a structure-driven framework for predicting microbiome interactions with alternative proteins. It also highlights key research priorities for developing functional protein ingredients that support gut and metabolic health.