Protein-fermentation biomarkers in plasma and urine differ between bovine plasma protein and whey protein isolate in...

Microbial fermentation of undigested proteins in the large intestine can produce potentially harmful metabolites. Although protein intake increases large intestinal protein inflow, the effects of dietary protein composition and digestibility are largely unknown.

This study aimed to investigate the effects of protein sources differing in amino acid (AA) composition and digestibility on protein-fermentation biomarkers (primary outcomes), digesta transit, and gut microbiome composition (secondary outcomes), by contrasting protein and precursor AA delivery into the large intestine using 2 purified protein sources.

Fifteen healthy adults participated in a randomized, controlled, crossover dietary intervention consuming bovine plasma protein (BPP, poorly digestible) or whey protein isolate (WPI, highly digestible) at 30 g/d, divided over 3 meals, for 7 d. Intervention periods were separated by a 7-d washout. Plasma, urine, and fecal samples were analyzed for protein-fermentation biomarkers, followed by linear mixed-effects model analysis.

In vitro degree of hydrolysis did not differ between BPP and WPI (32.6 ± 1.38% compared with 26.3 ± 0.05%, P = 0.10). Postprandial plasma total AA concentrations were also similar (BPP: 8997 ± 2673 μM, WPI: 9787 ± 3380 μM, P = 0.57, n = 13). Compared with WPI, BPP consumption induced higher plasma concentrations of p-cresyl sulfate (41.0 ± 27.4 compared with 28.5 ± 19.6, P < 0.01), phenyl sulfate (2.1 ± 0.6 compared with 1.8 ± 0.4, P = 0.03), phenylacetyl-L-glutamine (PAG) (2.3 ± 1.5 compared with 1.7 ± 1.2, P < 0.01), and indoxyl sulfate (4.8 ± 1.8 compared with 3.6 ± 1.4, P = 0.03). Urinary p-cresyl sulfate (111.4 ± 63.6 compared with 90.9 ± 56.7, P = 0.03), phenyl sulfate (13.6 ± 6.1 compared with 9.7 ± 2.6, P = 0.03), and PAG concentrations (55.1 ± 32.2 compared with 41.6 ± 25.6, P = 0.01) were also higher during BPP consumption. Protein source did not affect fecal ammonia, branched-chain fatty acid, or microbial diversity. BPP consumption tended to prolong colonic transit time (11:54 hh:mm, P = 0.07).

Consumption of BPP resulted in higher plasma and urinary concentrations of aromatic AA-derived microbial metabolites than WPI. These differences were most likely driven by AA composition rather than digestibility, as in vitro digestibility and postprandial AA responses differed less than expected between the protein sources. This trial was registered at clinicaltrials.gov as NCT06161155.