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Our findings demonstrated that SCH could increase the thymus index and spleen index, decrease the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, increase the serum IgG and small intestinal sIgA levels, reduce small intestinal and colon tissue damage, and activate the nuclear factor-\u03baB (NF-\u03baB) pathway by increasing TRAF6 and IRAK1 protein levels, as well as the phosphorylation levels of I\u03baB\u03b1 and p65, thereby enhancing immunity. In addition, SCH alleviated the imbalance of the gut microbiota by altering the composition of the gut microbiota in immunosuppressed mice. At the genus level, when compared with the model group, the relative abundance of Dubosiella, Lachnospiraceae, and Ligilactobacillus increased, while that of Lactobacillus, Bacteroides, and Turicibacter decreased in the SCH groups. Moreover, 26 potential bioactive peptides were identified by oligopeptide sequencing and bioactivity prediction. This study\u2019s findings thus provide an experimental basis for further development of SCH as a nutritional supplement to alleviate immunosuppression induced by Cy as well as provides a new idea for alleviating intestinal damage induced by Cy.<\/jats:p>","DOI":"10.3390\/foods12081604","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T05:59:33Z","timestamp":1681106373000},"page":"1604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sea Cucumber Hydrolysate Alleviates Immunosuppression and Gut Microbiota Imbalance Induced by Cyclophosphamide in Balb\/c Mice through the NF-\u03baB Pathway"],"prefix":"10.3390","volume":"12","author":[{"given":"Jing","family":"Mao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9707-2905","authenticated-orcid":false,"given":"Shunqin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RongRong","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-7459","authenticated-orcid":false,"given":"Yan","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0629-8421","authenticated-orcid":false,"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"China-Russia Agricultural Processing Joint Laboratory, Tianjin Agricultural University, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.foodchem.2017.10.087","article-title":"Immunomodulatory and anticancer protein hydrolysates (peptides) from food proteins: A review","volume":"245","author":"Chalamaiah","year":"2018","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41579-018-0036-x","article-title":"Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier","volume":"16","author":"Martens","year":"2018","journal-title":"Nat. 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