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Alamandine (Ala) and MrgD are novel members of the renin angiotensin system (RAS). This study tested the hypothesis that Ala restores the colon epithelial barrier integrity in ageing via modulating gut\u2013BM axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Mice, 2\u20133 (Young) or 22\u201324\u2009months (Old), were treated with saline or Ala by using Osmotic pumps. The intestinal permeability was evaluated using FITC\u2010dextran. Lgr5\n                      <jats:sup>+<\/jats:sup>\n                      Olfm4\n                      <jats:sup>+<\/jats:sup>\n                      intestinal stem cells (ISCs), Wnt3a and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin were evaluated by immunohistochemistry or western blotting. Faecal microbiome was analysed by 16S rRNA sequencing. Monocyte\u2010macrophages were characterized by flow cytometry. Caecal or serum bacterial metabolites were analysed and the caecal supernatants (CS) were tested for myelopoietic potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      MrgD was expressed in ISCs, which was decreased in the Old. Increased intestinal permeability in ageing was reversed by Ala. In the colon organoids, Ala increased Wnt3a levels and this was antagonized by NF449, SQ22536 or 666\u201015. Ala restored phospho\u2010CREB and active\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin levels that were decreased in the Old colon\u2010organoids. Ala increased the richness and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010diversity of the microbiota with decreased\n                      <jats:italic>Bacillota<\/jats:italic>\n                      \/\n                      <jats:italic>Bacteroidota<\/jats:italic>\n                      in ageing. Ala decreased the CD80\n                      <jats:sup>+<\/jats:sup>\n                      and increased CX3CR\n                      <jats:sup>+<\/jats:sup>\n                      macrophages in the Old colons. Old\u2010CS induced myelopoiesis in BM cells with higher number of pro\u2010inflammatory macrophages, which was prevented by Ala treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Targeting Ala\/MrgD pathway is a promising approach for ameliorating the inflammatory stress in ageing by restoring homeostasis in the gut\u2013BM inter\u2010organ communication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70656","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:00:10Z","timestamp":1789624810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alamandine\/MrgD pathway modulates gut\u2013bone marrow axis in ageing"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7079-3750","authenticated-orcid":false,"given":"Kishore","family":"Chittimalli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Health and Human Sciences North Dakota State University  Fargo North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2513-3785","authenticated-orcid":false,"given":"Henryata E.","family":"Rozario","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Health and Human Sciences North Dakota State University  Fargo North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Health and Human Sciences North Dakota State University  Fargo North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-507X","authenticated-orcid":false,"given":"Zachary L.","family":"McAdams","sequence":"additional","affiliation":[{"name":"University of Missouri Metagenomics Center, Department of Pathobiology and Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Adkins","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences University of North Dakota  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3053-7269","authenticated-orcid":false,"given":"Aaron C.","family":"Ericsson","sequence":"additional","affiliation":[{"name":"University of Missouri Metagenomics Center, Department of Pathobiology and Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-3693","authenticated-orcid":false,"given":"Yagna P. 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