Eggshell membrane modulates gut microbiota to prevent murine pre‐cachexia through suppression of T helper cell differentiation

• DOI: 10.1002/jcsm.13019
• Publication Date: 2022-06-20T02:59:07Z
• Authors: Huijuan Jia; Weida Lyu; Kazuki Hirota; Eri Saito; Moe Miyoshi; Hirohiko Hohjoh; Kyohei Furukawa; Kenji Saito; Makoto Haritani; Akashi Taguchi; Yukio Hasebe; Hisanori Kato
• Keywords: NEFA

Abstract Background Cachexia is a life‐threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 ( Il10 ) gene transfer known to improve cachexia by downregulating Il6 . Here, we used an IL10‐knockout mouse model simulate and investigate the effects of eggshell membrane (ESM), resistant protein, on general pre‐cachexia symptoms, which particularly important for development therapeutics. Methods Five‐week‐old male C57BL6/J mice were fed AIN‐93G powdered diet (WT), 5‐week‐old B6.129P2‐Il10 < tm1Cgn>/J (IL10 −/− either (KO) 8% ESM‐containing (KOE) 28 weeks. The tissue weight levels anaemia‐, blood glucose‐, lipid metabolism‐, muscular colonic inflammation‐related biochemical markers measured. Transcriptomic analysis liver colon mucus proteomic skeletal muscle performed. Ingenuity Pathway Analysis was identify molecular pathways networks. Caecal short‐chain fatty acids (SCFAs) identified using HPLC, caecal bacteria DNA subjected metagenomic analysis. Flow cytometry performed measure CD4 + IL17 T cells mesenteric lymph nodes. Results body weight, gastrocnemius fat tissues, weight/length ratio, plasma HDL NEFA, PECAM‐1 P 0.01), glucose mucosal myeloperoxidase activity 0.05) helper (Th) 17 cell abundance = 0.071) improved KOE over KO mice. Proteomic indicated protective role ESM weakness maintenance formation (>1.5‐fold). revealed that supplementation suppressed LPS/IL1‐mediated inhibition RXR function pathway downregulated expression chemokines Th differentiation‐related 0.01) suppressing upstream BATF pathway. intestinal microenvironment ameliorated microbial alpha diversity microbiota associated with degree inflammation increased level total organic acids, SCFAs butyrate (2.3‐fold), could inhibit Th1 Th17 production. Conclusions chief symptoms cachexia, including anorexia, lean mass, wasting reduced physical function. also inflammation, metabolism dysbiosis. These results along differentiation be beneficial and, subsequently, attenuation pre‐cachexia. Our findings provide insights into potential complementary interventions prevention.