Digestive enzymes, such as proteases and lipases, are widely recognized for their crucial roles in the ripening and production of fermented foods. Digestive enzymes are also used as supplements in nonruminant livestock to enhance feed digestion and promote animal growth. However, information on the effects of exogenous digestive enzymes on gut health and disease remains limited. Notably, recent studies show that consuming proteases and lipases can increase the levels of beneficial bacteria and short-chain fatty acids in rodent gut. These findings led us to hypothesize that intestinal proteases and lipases play beneficial roles by enriching beneficial bacteria. To examine this hypothesis, we reviewed recent studies on the potential effects of exogenous digestive enzymes on gut microbiota composition and overall health. Consistent with the hypothesis, all 13 studies in this review reported significant improvements in animal gut microbiota composition with the dietary supplementation of proteases and lipases. Additionally, the possible mechanisms of the prebiotic-like effects of the enzymes through increased nutrient digestion were discussed. This review explores how exogenous proteases and lipases influence gut microbiota composition and overall health. This is the first review to provide insights into the potential roles of exogenous digestive enzymes as prebiotics.

Introduction We examined the effect of 5.0 g/day of collagen peptide (CP) or collagen peptide fermented with Aspergillus sojae (FCP) on skin pigmentation in healthy participants. Methods In this randomized, double-blind, placebo-controlled study, 44 men and women aged 25–63 years were placed into three groups by stratified random allocation and treated with CP, FCP, or placebo (PL) at 5.0 g/day for 3 months. Their skin condition was measured monthly from baseline to 3 months of intake. Results No adverse events were identified in any group. The CP group showed a significant reduction in pigmented patches and redness after 1 and 3 months of intake, respectively. In the FCP group, pigmented macules were significantly reduced after 1 month, and pigmented patches after 2 months. Both the all-ages analysis and the hierarchical analysis below 55 years old yielded similar results. Conclusion Intake of 5.0 g/day of FCP for 3 months is safe. CP and FCP intake is useful for suppressing pigmentation. In addition, CP intake may be useful for reducing redness. These results suggest a new beneficial effect on the skin of CP supplementation. Trial Registration UMIN clinical trials registry system, UMIN000040736.

Although results of recent studies suggest that fermented foods strongly affect the gut microbiota composition and that they relieve inflammatory bowel disease symptoms, some reports have described that fermented foods increase some inflammation markers based on differences in fermented food materials. This study evaluated the effects of fermented plant extract (FPE) on dextran sulfate sodium (DSS)-induced colitis in mice and the effects on fecal microbiota composition in humans. Mice fed 5% FPE with 3% DSS (FPE group) showed no body weight loss, atrophy of colonic length, or bloody stool, similar to mice fed a basal diet (negative group), whereas mice fed 3% DSS (positive group) exhibited those effects. Concentrations of inflammation markers IL-6 and TNF-α were not significantly different between FPE and negative groups; however, those concentrations became higher in the positive group. 16S ribosomal RNA gene sequencing was used to characterize fecal microbiota in healthy women before and after 3-month FPE supplementation. The FPE supplementation induced increases in Firmicutes phyla and in Clostridiales order, which play a central role in inflammation suppression. These results suggest that FPE enhances Clostridiales growth in the gut and that it has an anti-inflammatory effect.