{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:54:17Z","timestamp":1791831257455,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Project on Agricultural Biological Breeding","award":["2023ZD0404905"],"award-info":[{"award-number":["2023ZD0404905"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["2023ZD0404905"],"award-info":[{"award-number":["2023ZD0404905"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The establishment of early gut microbiota is crucial for host health. Lactoferrin (LF), which is present in breast milk, positively impacts gut microbiota composition. However, the effect of lactation LF on the establishment and composition of early gut microbiota in different disease models in adulthood remains unclear. Methods: Lactation-LF-deficient mice were established using systemically LF\u2013knocked-out maternal mice. This study assessed the maturity of the gut microbiota in LF feeding-deficient mice in relation to age and changes in the gut microbiota in adult high-fat diet (HFD)-induced obesity, dextran sodium sulfate (DSS)-induced acute colitis, and chronic unpredictable mild stress (CUMS)-induced depression models. Results: Compared to LF intake during lactation, LF deficiency during lactation increased the abundance of potentially pathogenic bacteria in the gut, resulting in abnormal microbial maturation. LF intake during lactation aggravated gut microbiota dysbiosis induced via HFD, DSS, and CUMS in adulthood and may change the function of Enterorhabdus, GCA-900066575, Peptococcus, Tuzzerella, Akkermansia, and Desulfovibrio. Comparing the different models revealed that bacteria that were jointly upregulated via HFD and DSS exhibited increased levels of inflammation and oxidation. LF deficiency during lactation may weaken the association between an HFD and inflammatory bowel disease (IBD). The changing trends in many gut microbes caused by DSS and HFD were opposite to those that changed with age. Conclusions: Lactoferrin deficiency increases the abundance of potential pathogens and disrupts microbial maturation. This lack of LF exacerbates dysbiosis in models of obesity, colitis, and depression. Regulating the gut microbiota according to the rules of microbial succession during the maturation process of gut microbiota may improve gut microbiota dysbiosis in patients with obesity and IBD.<\/jats:p>","DOI":"10.3390\/nu17132248","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T10:03:27Z","timestamp":1751882607000},"page":"2248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Lactation Lactoferrin Deficiency on Intestinal Microbiota in Different Mice Models"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8426-6908","authenticated-orcid":false,"given":"Wenli","family":"Wang","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"An","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6951-3849","authenticated-orcid":false,"given":"Qingyong","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Biological Sciences, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5354-1973","authenticated-orcid":false,"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-genet-110711-155532","article-title":"The Relationship Between the Human Genome and Microbiome Comes into View","volume":"51","author":"Goodrich","year":"2017","journal-title":"Annu. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.gpb.2018.10.002","article-title":"Intestinal Microbiota in Early Life and Its Implications on Childhood Health","volume":"17","author":"Zhuang","year":"2019","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101943","DOI":"10.1016\/j.cpr.2020.101943","article-title":"The gut microbiota in anxiety and depression\u2014A systematic review","volume":"83","author":"Simpson","year":"2021","journal-title":"Clin. Psychol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.chom.2020.06.001","article-title":"High-Fat Diet and Antibiotics Cooperatively Impair Mitochondrial Bioenergetics to Trigger Dysbiosis that Exacerbates Pre-inflammatory Bowel Disease","volume":"28","author":"Lee","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1038\/s41380-022-01787-1","article-title":"High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens","volume":"27","author":"Tsai","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41575-022-00634-6","article-title":"Depression and anxiety in inflammatory bowel disease: Epidemiology, mechanisms and treatment","volume":"19","author":"Bisgaard","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wu, X., Xu, J., Li, J., Deng, M., Shen, Z., Nie, K., Luo, W., Zhang, C., Ma, K., and Chen, X. (2023). Bacteroides vulgatus alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1287271"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114143","DOI":"10.1016\/j.foodres.2024.114143","article-title":"Unlocking the power of Lactoferrin: Exploring its role in early life and its preventive potential for adult chronic diseases","volume":"182","author":"Wang","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wang, W., Cheng, Z., Wang, X., An, Q., Huang, K., Dai, Y., Meng, Q., and Zhang, Y. (2023). Lactoferrin deficiency during lactation increases the risk of depressive-like behavior in adult mice. BMC Biol., 21.","DOI":"10.1186\/s12915-023-01748-2"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1016\/j.cell.2021.04.026","article-title":"SnapShot: Microbiota effects on host physiology","volume":"184","author":"Hill","year":"2021","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nature11550","article-title":"Diversity, stability and resilience of the human gut microbiota","volume":"489","author":"Lozupone","year":"2012","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/0884533615609899","article-title":"Gut Microbiome: What we do and don\u2019t know","volume":"30","author":"Cresci","year":"2015","journal-title":"Nutr. Clin. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.18632\/aging.202525","article-title":"Age-dependent remodeling of gut microbiome and host serum metabolome in mice","volume":"13","author":"Wu","year":"2021","journal-title":"Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrgastro.2012.144","article-title":"Microbial contact during pregnancy, intestinal colonization and human disease","volume":"9","author":"Rautava","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12524","DOI":"10.1111\/jpi.12524","article-title":"Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high-fat diet-fed mice","volume":"65","author":"Yin","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"G589","DOI":"10.1152\/ajpgi.00488.2011","article-title":"Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine","volume":"303","author":"Derrien","year":"2012","journal-title":"Am. J. Physiol. Gastroint. Liver Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, B., Kong, Q., Li, X., Zhao, J., Zhang, H., Chen, W., and Wang, G. (2020). A High-Fat Diet Increases Gut Microbiota Biodiversity and Energy Expenditure Due to Nutrient Difference. Nutrients, 12.","DOI":"10.3390\/nu12103197"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xu, H.M., Huang, H.L., Liu, Y.D., Zhu, J.Q., Zhou, Y.L., Chen, H.T., Xu, J., Zhao, H.L., Guo, X., and Shi, W. (2021). Selection strategy of dextran sulfate sodium-induced acute or chronic colitis mouse models based on gut microbial profile. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02342-8"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Magne, F., Gotteland, M., Gauthier, L., Zazueta, A., Pesoa, S., Navarrete, P., and Balamurugan, R. (2020). The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?. Nutrients, 12.","DOI":"10.3390\/nu12051474"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mariat, D., Firmesse, O., Levenez, F., Guimaraes, V., Sokol, H., Dore, J., Corthier, G., and Furet, J.P. (2009). The Firmicutes\/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-123"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jfma.2018.07.009","article-title":"The gut microbiome in obesity","volume":"118","author":"Tseng","year":"2019","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yee, S., Choi, H., Seon, J., Ban, Y., Kim, M., Seo, J., Seo, J.H., Kim, S., Moon, S.H., and Yun, C. (2023). Axl alleviates DSS-induced colitis by preventing dysbiosis of gut microbiota. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-32527-2"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12753","DOI":"10.1021\/acs.jafc.1c05793","article-title":"In Vitro and In Vivo Studies Reveal that Hesperetin-7-O-glucoside, a Naturally Occurring Monoglucoside, Exhibits Strong Antiinflammatory Capacity","volume":"69","author":"Wu","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1875796","DOI":"10.1080\/19490976.2021.1875796","article-title":"Blautia-a new functional genus with potential probiotic properties?","volume":"13","author":"Liu","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104726","DOI":"10.1016\/j.jff.2021.104726","article-title":"Neuroprotective effect of fucoidan by regulating gut-microbiota-brain axis in alcohol withdrawal mice","volume":"86","author":"Xue","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Parker, B.J., Wearsch, P.A., Veloo, A.C.M., and Rodriguez-Palacios, A. (2020). The Genus Alistipes: Gut Bacteria with Emerging Implications to Inflammation, Cancer, and Mental Health. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00906"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yu, M., Yue, J., Hui, N., Zhi, Y., Hayat, K., Yang, X., Zhang, D., Chu, S., and Zhou, P. (2021). Anti-Hyperlipidemia and Gut Microbiota Community Regulation Effects of Selenium-Rich Cordyceps militaris Polysaccharides on the High-Fat Diet-Fed Mice Model. Foods, 10.","DOI":"10.3390\/foods10102252"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7817","DOI":"10.1039\/D0FO01418D","article-title":"Grape seed proanthocyanidin extract ameliorates dextran sulfate sodium-induced colitis through intestinal barrier improvement, oxidative stress reduction, and inflammatory cytokines and gut microbiota modulation","volume":"11","author":"Sheng","year":"2020","journal-title":"Food Funct."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jare.2023.08.008","article-title":"Targeting Desulfovibrio vulgaris flagellin-induced NAIP\/NLRC4 inflammasome activation in macrophages attenuates ulcerative colitis","volume":"52","author":"An","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1800962","DOI":"10.1002\/mnfr.201800962","article-title":"Combined Consumption of Beef-Based Cooked Mince and Sucrose Stimulates Oxidative Stress, Cardiac Hypertrophy, and Colonic Outgrowth of Desulfovibrionaceae in Rats","volume":"63","author":"Boon","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.7150\/ijbs.86717","article-title":"High-fat diet promotes colitis-associated tumorigenesis by altering gut microbial butyrate metabolism","volume":"19","author":"Shao","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.nut.2018.10.002","article-title":"Probiotics improve gut microbiota dysbiosis in obese mice fed a high-fat or high-sucrose diet","volume":"60","author":"Kong","year":"2019","journal-title":"Nutrition"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, M., Zhang, S., Zhong, R., Wan, F., Chen, L., Liu, L., Yi, B., and Zhang, H. (2021). Olive Fruit Extracts Supplement Improve Antioxidant Capacity via Altering Colonic Microbiota Composition in Mice. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.645099"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1021\/acs.jafc.1c02925","article-title":"Lactobacillus rhamnosus LRa05 Ameliorate Hyperglycemia through a Regulating Glucagon-Mediated Signaling Pathway and Gut Microbiota in Type 2 Diabetic Mice","volume":"69","author":"Wu","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dang, Y., Ma, C., Chen, K., Chen, Y., Jiang, M., Hu, K., Li, L., Zeng, Z., and Zhang, H. (2023). The Effects of a High-Fat Diet on Inflammatory Bowel Disease. Biomolecules, 13.","DOI":"10.3390\/biom13060905"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100042","DOI":"10.1016\/j.fochms.2021.100042","article-title":"Exopolysaccharides from a Scandinavian fermented milk viili increase butyric acid and Muribaculum members in the mouse gut","volume":"3","author":"Yamane","year":"2021","journal-title":"Food Chem. Mol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1039\/C9FO00014C","article-title":"A ropy exopolysaccharide producing strain Bifidobacterium longum subsp. longum YS108R alleviates DSS-induced colitis by maintenance of the mucosal barrier and gut microbiota modulation","volume":"10","author":"Yan","year":"2019","journal-title":"Food Funct."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Hou, D., Fu, Y., Xue, Y., Guan, X., and Shen, Q. (2021). Adzuki Bean Alleviates Obesity and Insulin Resistance Induced by a High-Fat Diet and Modulates Gut Microbiota in Mice. Nutrients, 13.","DOI":"10.3390\/nu13093240"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6259381","DOI":"10.1155\/2021\/6259381","article-title":"Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis","volume":"2021","author":"Sun","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12944-022-01711-0","article-title":"Potential novel biomarkers in small intestine for obesity\/obesity resistance revealed by multi-omics analysis","volume":"21","author":"Pang","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1007\/s00394-017-1542-8","article-title":"Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice","volume":"57","author":"Henning","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1038\/s41467-023-39403-7","article-title":"Gut microbiota Turicibacter strains differentially modify bile acids and host lipids","volume":"14","author":"Lynch","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14718","DOI":"10.1021\/acs.jafc.2c06177","article-title":"Orally Administered Ginkgolide C Attenuates DSS-Induced Colitis by Maintaining Gut Barrier Integrity, Inhibiting Inflammatory Responses, and Regulating Intestinal Flora","volume":"70","author":"Xu","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Moorthy, M., Sundralingam, U., and Palanisamy, U.D. (2021). Polyphenols as Prebiotics in the Management of High-Fat Diet-Induced Obesity: A Systematic Review of Animal Studies. Foods, 10.","DOI":"10.3390\/foods10020299"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109511","DOI":"10.1016\/j.foodres.2020.109511","article-title":"Monascus purpureus-fermented common buckwheat protects against dyslipidemia and non-alcoholic fatty liver disease through the regulation of liver metabolome and intestinal microbiome","volume":"136","author":"Huang","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4161\/gmic.2.4.17863","article-title":"Intestinal dysbiosis in inflammatory bowel disease","volume":"2","author":"Kaur","year":"2011","journal-title":"Gut Microbes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s10020-025-01094-9","article-title":"Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia","volume":"31","author":"Wang","year":"2025","journal-title":"Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1038\/s41564-024-01735-5","article-title":"Spatial mapping of mobile genetic elements and their bacterial hosts in complex microbiomes","volume":"9","author":"Grodner","year":"2024","journal-title":"Nat. Microbiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/13\/2248\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:06:01Z","timestamp":1760033161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/13\/2248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":48,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["nu17132248"],"URL":"https:\/\/doi.org\/10.3390\/nu17132248","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]}}}