Protein supplementation and the gut microbiome, metabolites, integrity, and inflammation in human adults: A scoping review of current evidence and gaps

This scoping review systematically evaluated the effects of protein supplements on the gut microbiome, metabolites, integrity, and inflammation. Studies investigating plant- or animal-based protein supplements in adults were identified from five electronic databases. Data were thematically synthesized; study quality was appraised using the Mixed Methods Appraisal Tool. Fourteen studies were included: whey protein (n=9), pea protein (n=3), soy protein (n=2), and casein protein (n=1). Doses ranged from 10-85 g/day (whey), 7.3-25 g/day or 30% of total energy (pea), and 15-40 g/day (soy). Intervention durations ranged from 4 days to 12 weeks (whey), 31 days to 12 weeks (pea), and 17-21 days (soy). Most studies found minimal effects on gut microbial alpha- and beta-diversity, although taxa-specific shifts were observed. Whey protein was associated with increases in Veillonellaceae, Bacteroides, and Bifidobacterium, while pea protein showed reductions in Firmicutes and Bacteroidota. Functional and metabolomic outcomes were inconsistent, with some evidence of altered amino acid-derived metabolites and polyphenol-related compounds, particularly in studies involving co-interventions. No consistent effects on gut barrier integrity or inflammatory markers were observed. Importantly, protein supplementation was rarely evaluated in isolation, with many studies incorporating co-interventions (e.g., exercise, caloric restriction, fermentation, or pre-/probiotic and polyphenol enrichment) that may independently influence the gut microbiome. As such, observed effects likely reflect combined exposures rather than protein alone, varying by protein type, dose, co-supplementation, population characteristics, and study conditions. Well-controlled studies that isolate protein effects are needed to clarify the mechanistic and clinical relevance of protein supplementation on gut health.