The beneficial potential of protein hydrolysates as prebiotic for probiotics and its biological activity: a review

Figures & data

Figure 1. Diagram of the proteolysis system of LAB.

Table 1. Effect of protein hydrolysates on probiotics.

Protein hydrolysate sources	Protease	Molecular weight	Probiotics	Effect/Functionality	References
Casein	Alcalase, chymotrypsin and trypsin	<1 kDa	B. infantis, B. breve and B. longum	Effects stimulating growth	Proulx et al. 1994
	Alcalase	<2 kDa	L. lactis ssp. cremoris strains (E8 and Wg2) and L. lactis ssp. lactis 1076	Effects stimulating growth; Increasing lactic acid production	St-Gelais et al. 1993
	Trypsin	<1 kDa	B. bifidum and B. longum	Effects stimulating growth	Poch and Bezkorovainy 1991
	Alcalase, flavorzyme, neutrase, papain and trypsin	<3 kDa	L. bulgaricus and S. thermophilus	Growth-stimulating effect; Increasing lactic acid production	Zhang et al. 2011
	Pepsin, trypsin, α-chymotrypsin	<12 kDa	Lactobacillus gasseri	Effects stimulating growth	Arakawa et al. 2015
	Protease	/	L. acidophilus	Effects stimulating growth	Masuda et al. 2003
Caseinomacro­peptide	Peptic and tryptic	/	B. animalis subsp. Lactis BB-12, Bifido. thermophilum RBL67, Bifido. longum R0175, L. rhamnosus GG, L. rhamnosus RW-9595M and L. plantarum 299 V	Effects stimulating growth	Robitaille and Champagne 2014
	Papain	/	S. thermophilus and B. animalis subsp. lactis	Effects stimulating growth	Tian et al. 2015
	Alcalase and Flavorzyme	<1 kDa	B. bifidum	Effects stimulating growth	Fukudome et al. 2021
whey protein	Alkaline protease	/	B. lactis Probio-M8	Antioxidant lyoprotectant	Wang et al. 2022
	Trypsin	/	S. salivarius ssp. thermophilus, L. acidophilu, B. bifidum, L. delbrueckii ssp. bulgaricus	Antioxidant capacity; Protection of probiotics	Krunić and Rakin 2022
	Tryptic	/	B. longum, B. bifidum, B. breve, B. infantis and L. acidophilus	Effects stimulating growth	Kafley et al. 2010
	Pepsin and pancreatin	>10 kDa	L. acidophilus NCFM	Effects stimulating growth; Increasing yield of short-chain fatty acids	Feng et al. 2022
	Aqueous extract of Cynara cardunculus	<1 kDa	L. acidophilus and B. animalis	Effects stimulating growth; Regulating the gut microbiota	Yu et al. 2016
	Proteinase K	/	S. thermophilus	Effects stimulating growth	Zisu and Shah 2003
	Alcalase	/	Bifidobacterium L80	Effects stimulating growth	Wang et al. 2021
	α-Amylase and pepsin	<1 kDa	L. rhamnosus CICC22152	Protective agent	Xie et al. 2023
Milk	Thermolysin	410 kDa	L. acidophilus, L. helveticus, L. delbrueckii ssp. bulgaricus, and S. thermophilus	Increasing proteolytic activity; Increasing ACE-inhibitory activity	Gandhi and Shah 2014
Soybean protein	Alkaline proteinase	<5 kDa	S. thermophilus ST	Effects stimulating growth	Zhao et al. 2013
	Pepsin and pancreatin	<0.5 kDa	L. rhamnosus	Effects stimulating growth; Increasing yield of short-chain fatty acids	Zhang et al. 2021a
	Pepsin and pancreatin	/	Limosilactobacillus reuteri LR08	Effects stimulating growth; Increasing yield of short-chain fatty acids	Zhang et al. 2022
	Pepsin and trypsin	/	B. animalis subsp. animalis JCM 1190	Promoting growth and metabolism	Li et al. 2021a
	Alkaline and neutral protease	0.15 − 1 kDa	Lactobacillus and Phascolarctobacterium	Effects stimulating growth	Li et al. 2021b
	Alcalase	<14.4 kDa	S. thermophilus	Effects stimulating growth; Increasing organic acid production	Sun et al. 2021
Quinoa protein	Pepsin and pancreatin	/	Ruminococcus, Turicibacter and Streptococcus	Increasing yield of short-chain fatty acids; Increasing the abundance of probiotics	Fan et al. 2023
Egg white	Aspergillus oryzae	/	L. plantarum NRRL B-4496, L. acidophilus NRRL B-449, and L. reuteri B-14171	Effects stimulating growth	Solval et al. 2019
Poultry feathers	/	/	Bifidobacterium	Activate aminopeptidases and support growth	Meli et al. 2013
Keratin	Proteinase	/	L. plantarum	Activate aminopeptidases and support growth	Fadda et al. 1999

Proulx, M., P. Ward, S. F. Gauthier, and D. Roy. 1994. Comparison of bifidobacterial growth-promoting activity of ultrafiltered casein hydrolysate fractions. Le Lait 74 (2):139–152. doi:10.1051/lait:1994212.

 Google Scholar

St-Gelais, D., D. Roy, S. Haché, M. L. Desjardins, and S. F. Gauthier. 1993. Growth of nonproteolytic Lactococcus lactis in culture medium supplemented with different casein hydrolyzates. Journal of Dairy Science 76 (11):3327–3337. doi:10.3168/jds.S0022-0302(93)77670-5.

 Web of Science ®Google Scholar

Poch, M., and A. Bezkorovainy. 1991. Bovine milk-casein trypsin digest is a growth enhancer for the genus Bifidobacterium. Journal of Agricultural and Food Chemistry 39 (1):73–77. doi:10.1021/jf00001a013.

 Web of Science ®Google Scholar

Zhang, Q. L., J. Y. Ren, H. F. Zhao, M. M. Zhao, J. Y. Xu, and Q. Z. Zhao. 2011. Influence of casein hydrolysates on the growth and lactic acid production of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus. International Journal of Food Science & Technology 46 (5):1014–1020. doi:10.1111/j.1365-2621.2011.02578.x.

 Web of Science ®Google Scholar

Arakawa, K., K. Matsunaga, S. Takihiro, A. Moritoki, S. Ryuto, Y. Kawai, T. Masuda, and T. Miyamoto. 2015. Lactobacillus gasseri requires peptides, not proteins or free amino acids, for growth in milk. Journal of Dairy Science 98 (3):1593–1603. doi:10.3168/jds.2014-8860.

 PubMed Web of Science ®Google Scholar

Masuda, T., R. Taguchi, T. Kabuki, H. Nakajima, and T. Itoh. 2003. Improvement of the growth of Lactobacillus acidophilus in milk by addition of enzymatically digested casein. Milchwissenschaft-Milk Science International 58:124–127.

 Google Scholar

Robitaille, G., and C. P. Champagne. 2014. Growth-promoting effects of pepsin- and trypsin-treated caseinomacropeptide from bovine milk on probiotics. The Journal of Dairy Research 81 (3):319–324. doi:10.1017/S0022029914000247.

 PubMed Web of Science ®Google Scholar

Tian, Q., T. T. Wang, X. Tang, M. Z. Han, X. J. Leng, and X. Y. Mao. 2015. Developing a potential prebiotic of yogurt: Growth of Bifidobacterium and yogurt cultures with addition of glycomacropeptide hydrolysate. International Journal of Food Science & Technology 50 (1):120–127. doi:10.1111/ijfs.12611.

 Web of Science ®Google Scholar

Fukudome, H., T. Yamaguchi, J. Higuchi, A. Ogawa, Y. Taguchi, J. Li, T. Kabuki, K. Ito, and F. Sakai. 2021. Large-scale preparation and glycan characterization of sialylglycopeptide from bovine milk glycomacropeptide and its bifidogenic properties. Journal of Dairy Science 104 (2):1433–1444. doi:10.3168/jds.2019-17865.

 PubMed Web of Science ®Google Scholar

Wang, H. Q., T. Huang, K. L. Liu, J. Yu, G. Q. Yao, W. Y. Zhang, H. P. Zhang, and T. S. Sun. 2022. Protective effects of whey protein hydrolysate on Bifidobacterium animalis ssp. lactis Probio-M8 during freeze-drying and storage. Journal of Dairy Science 105 (9):7308–7321. doi:10.3168/jds.2021-21546.

 PubMed Web of Science ®Google Scholar

Krunić, T. Ž., and M. B. Rakin. 2022. Enriching alginate matrix used for probiotic encapsulation with whey protein concentrate or its trypsin-derived hydrolysate: Impact on antioxidant capacity and stability of fermented whey-based beverages. Food Chemistry 370:130931. doi:10.1016/j.foodchem.2021.130931.

 PubMed Web of Science ®Google Scholar

Kafley, S., W. S. Kim, H. Kumura, and K. Shimazaki. 2010. Growth performance of whey protein hydrolysates in the media on different strains of probiotic bacteria. Milchwissenschaft-Milk Science International 65 (3):245–248.

 Google Scholar

Feng, C. S., L. Tian, H. Hong, Q. Y. Wang, X. Zhan, Y. K. Luo, and Y. Q. Tan. 2022. In vitro gut fermentation of whey protein hydrolysate: An evaluation of its potential modulation on infant gut microbiome. Nutrients 14 (7):1374. doi:10.3390/nu14071374.

 PubMed Web of Science ®Google Scholar

Yu, Y. J., M. Amorim, C. Marques, C. Calhau, and M. Pintado. 2016. Effects of whey peptide extract on the growth of probiotics and gut microbiota. Journal of Functional Foods 21:507–516. doi:10.1016/j.jff.2015.10.035.

 Web of Science ®Google Scholar

Zisu, B., and N. P. Shah. 2003. Effects of pH, temperature, supplementation with whey protein concentrate, and adjunct cultures on the production of exopolysaccharides by Streptococcus thermophilus 1275. Journal of Dairy Science 86 (11):3405–3415. doi:10.3168/jds.S0022-0302(03)73944-7.

 PubMed Web of Science ®Google Scholar

Wang, B., Y. Yang, X. Bian, H.-N. Guan, L.-L. Liu, X.-X. Li, Q.-Q. Guo, W. Piekoszewski, F.-L. Chen, N. Wu, et al. 2021. Proliferation of Bifidobacterium L80 under different proportions of milk protein hydrolysate. Microbial Cell Factories 20 (1):213. doi:10.1186/s12934-021-01702-3.

 PubMed Web of Science ®Google Scholar

Xie, H. X., Y. Liao, M. W. Woo, H. Xiong, and Q. Zhao. 2023. Whey protein hydrolysates as prebiotic and protective agent regulate growth and survival of Lactobacillus rhamnosus CICC22152 during spray/freeze-drying, storage and gastrointestinal digestion. Journal of the Science of Food and Agriculture 103 (3):1237–1246. doi:10.1002/jsfa.12218.

 PubMed Web of Science ®Google Scholar

Gandhi, A., and N. P. Shah. 2014. Cell growth and proteolytic activity of Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus delbrueckii ssp. bulgaricus, and Streptococcus thermophilus in milk as affected by supplementation with peptide fractions. International Journal of Food Sciences and Nutrition 65 (8):937–941. doi:10.3109/09637486.2014.945154.

 PubMed Web of Science ®Google Scholar

Zhao, H. F., F. L. Bai, F. Zhou, P. Walczak, X. N. Jiang, and B. L. Zhang. 2013. Characterization of soybean protein hydrolysates able to promote the proliferation of Streptococcus Thermophilus ST. Journal of Food Science 78 (4):M575–M581. doi:10.1111/1750-3841.12075.

 PubMed Web of Science ®Google Scholar

Zhang, C., Y. X. Zhang, G. R. Liu, W. H. Li, S. Q. Xia, H. Li, and X. Q. Liu. 2021. Effects of soybean protein isolates and peptides on the growth and metabolism of Lactobacillus rhamnosus. Journal of Functional Foods 77:104335. doi:10.1016/j.jff.2020.104335.

 Web of Science ®Google Scholar

Zhang, C., S. Xia, Y. Zhang, S. Zhu, H. Li, and X. Liu. 2022. Identification of soybean peptides and their effect on the growth and metabolism of Limosilactobacillus reuteri LR08. Food Chemistry 369:130923. doi:10.1016/j.foodchem.2021.130923.

 PubMed Web of Science ®Google Scholar

Li, W. H., H. Li, Y. X. Zhang, C. Zhang, J. Zhang, and X. Q. Liu. 2021. Differences in the gut microbiota composition of rats fed with soybean protein and their derived peptides. Journal of Food Science 86 (12):5452–5465. doi:10.1111/1750-3841.15948.

 PubMed Web of Science ®Google Scholar

Sun, Z.-H., M.-J. Yao, X. Bian, Q.-Q. Guo, H.-N. Guan, Y. Yang, B. Wang, Y.-G. Shi, W. Piekoszewski, X.-W. Yang, et al. 2021. The influence of soy protein hydrolysate (SPH) addition to infant formula powder on Streptococcus thermophilus proliferation and metabolism. Food Research International (Ottawa, Ont.) 141:110103. doi:10.1016/j.foodres.2020.110103.

 PubMed Web of Science ®Google Scholar

Fan, X., H. M. Guo, C. Teng, X. S. Yang, P. Y. Qin, A. Richel, L. Z. Zhang, C. Blecker, and G. X. Ren. 2023. Supplementation of quinoa peptides alleviates colorectal cancer and restores gut microbiota in AOM/DSS-treated mice. Food Chemistry 408:135196. doi:10.1016/j.foodchem.2022.135196.

 PubMed Web of Science ®Google Scholar

Solval, K. M., A. Chouljenko, A. Chotiko, and S. Sathivel. 2019. Growth kinetics and lactic acid production of Lactobacillus plantarum NRRL B-4496, L. acidophilus NRRL B-4495, and L. reuteri B-14171 in media containing egg white hydrolysates. Lwt 105:393–399. doi:10.1016/j.lwt.2019.01.058.

 Web of Science ®Google Scholar

Meli, F., C. Lazzi, E. Neviani, and M. Gatti. 2013. Effect of protein hydrolizates on growth kinetics and aminopeptidase activities of some Bifidobacterium species. Anaerobe 22:130–133. doi:10.1016/j.anaerobe.2013.05.003.

 PubMed Web of Science ®Google Scholar

Fadda, S., Y. Sanz, G. Vignolo, M. C. Aristoy, G. Oliver, and F. Toldrá. 1999. Characterization of muscle sarcoplasmic and myofibrillar protein hydrolysis caused by Lactobacillus plantarum. Applied and Environmental Microbiology 65 (8):3540–3546. doi:10.1089/oli.1.1999.9.359.

 PubMed Web of Science ®Google Scholar