{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:29:07Z","timestamp":1792196947861,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T00:00:00Z","timestamp":1655596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K11095"],"award-info":[{"award-number":["18K11095"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cachexia is a life\u2010threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 (<jats:italic>Il10<\/jats:italic>) gene transfer is known to improve cachexia by downregulating <jats:italic>Il6<\/jats:italic>. Here, we used an IL10\u2010knockout mouse model to simulate cachexia and investigate the effects of eggshell membrane (ESM), a resistant protein, on general pre\u2010cachexia symptoms, which is particularly important for the development of cachexia therapeutics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five\u2010week\u2010old male C57BL6\/J mice were fed an AIN\u201093G powdered diet (WT), and 5\u2010week\u2010old male B6.129P2\u2010Il10\u00a0&lt;\u00a0tm1Cgn&gt;\/J (IL10<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were fed either the AIN\u201093G diet (KO) or an 8% ESM\u2010containing diet (KOE) for 28\u00a0weeks. The tissue weight and levels of anaemia\u2010, blood glucose\u2010, lipid metabolism\u2010, and muscular and colonic inflammation\u2010related biochemical markers were measured. Transcriptomic analysis on liver and colon mucus and proteomic analysis on skeletal muscle were performed. Ingenuity Pathway Analysis was used to identify molecular pathways and networks. Caecal short\u2010chain fatty acids (SCFAs) were identified using HPLC, and caecal bacteria DNA were subjected to metagenomic analysis. Flow cytometry analysis was performed to measure the CD4<jats:sup>+<\/jats:sup> IL17<jats:sup>+<\/jats:sup> T cells in mesenteric lymph nodes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The body weight, weight of gastrocnemius muscle and fat tissues, colon weight\/length ratio, plasma HDL and NEFA, muscular PECAM\u20101 levels (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), plasma glucose and colonic mucosal myeloperoxidase activity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and T helper (Th) 17 cell abundance (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.071) were improved in KOE mice over KO mice. Proteomic analysis indicated the protective role of ESM in muscle weakness and maintenance of muscle formation (&gt;1.5\u2010fold). Transcriptomic analysis revealed that ESM supplementation suppressed the LPS\/IL1\u2010mediated inhibition of RXR function pathway in the liver and downregulated the colonic mucosal expression of chemokines and Th cell differentiation\u2010related markers (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) by suppressing the upstream BATF pathway. Analysis of the intestinal microenvironment revealed that ESM supplementation ameliorated the microbial alpha diversity and the abundance of microbiota associated with the degree of inflammation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and increased the level of total organic acids, particularly of SCFAs such as butyrate (2.3\u2010fold), which could inhibit Th1 and Th17 production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ESM supplementation ameliorated the chief symptoms of cachexia, including anorexia, lean fat tissue mass, skeletal muscle wasting and reduced physical function. ESM also improved colon and skeletal muscle inflammation, lipid metabolism and microbial dysbiosis. These results along with the suppressed differentiation of Th cells could be associated with the beneficial intestinal microenvironment and, subsequently, attenuation of pre\u2010cachexia. Our findings provide insights into the potential of ESM in complementary interventions for pre\u2010cachexia prevention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13019","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T02:59:07Z","timestamp":1655693947000},"page":"2088-2101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Eggshell membrane modulates gut microbiota to prevent murine pre\u2010cachexia through suppression of T helper cell differentiation"],"prefix":"10.1002","volume":"13","author":[{"given":"Huijuan","family":"Jia","sequence":"first","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weida","family":"Lyu","sequence":"additional","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Hirota","sequence":"additional","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Saito","sequence":"additional","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moe","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Hohjoh","sequence":"additional","affiliation":[{"name":"National Institute of Neuroscience NCNP  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyohei","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Saito","sequence":"additional","affiliation":[{"name":"Health Nutrition, Graduate School of Agricultural and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Haritani","sequence":"additional","affiliation":[{"name":"Environmental Science for Sustainable Development Graduate School of Agriculture and Life Sciences University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akashi","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Research Center for Advanced Science and Technology University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Hasebe","sequence":"additional","affiliation":[{"name":"ALMADO Inc.  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