{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:51:32Z","timestamp":1781675492482,"version":"3.54.5"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Omega-3 polyunsaturated fatty acids (PUFAs) have been widely reported to exert beneficial effects in type 1 diabetes mellitus (T1DM). However, the mechanisms by which Omega-3 PUFAs influence pancreatic islet function through the gut-islet axis remain incompletely understood. This study aimed to investigate whether Omega-3 PUFAs-associated alterations in gut microbiota composition and their metabolites are involved in the modulation of the pancreatic islet microenvironment in T1DM, and to explore the potential immunological mechanisms underlying these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fecal microbiota transplantation (FMT) was performed to evaluate the effects of Omega-3 PUFAs-associated gut microbiota in non-obese diabetic (NOD) mice. Immune cell composition and inflammatory status within pancreatic islets were analyzed using transcriptomic profiling, flow cytometry, and immunohistochemistry. Metabolomics analysis was performed to investigate the association among Omega-3 PUFAs, gut microbiota, and microbiota-related metabolites.\n                      <jats:italic>In vitro<\/jats:italic>\n                      co-culture systems were further established to evaluate the effects of selected metabolites on macrophage polarization and insulin production and secretion in pancreatic \u03b2-cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Omega-3 PUFAs treatment and FMT were associated with reduced islet inflammation and a marked enrichment of the\n                      <jats:italic>Eubacterium coprostanoligenes group<\/jats:italic>\n                      (\n                      <jats:italic>E. coprostanoligenes<\/jats:italic>\n                      ). Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18\u03b2-glycyrrhetinic acid (18\u03b2-GA) showed a strong association with\n                      <jats:italic>E. coprostanoligenes<\/jats:italic>\n                      , and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments suggested a potential involvement of\n                      <jats:italic>E. coprostanoligenes<\/jats:italic>\n                      in the metabolic conversion process related to 18\u03b2-GA. In co-culture systems, 18\u03b2-GA promoted macrophage polarization toward an M2-like phenotype, which was accompanied by increased insulin production and secretion in pancreatic \u03b2-cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that Omega-3 PUFAs-associated alterations in gut microbiota composition and 18\u03b2-GA-related metabolic changes may contribute to the modulation of the pancreatic immune microenvironment and \u03b2-cells function in T1DM. This study provides additional insights into lipid-microbiota-immune interactions relevant to T1DM and supports further investigation of microbiota-associated immune regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1871892","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:53:10Z","timestamp":1781671990000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Omega-3 polyunsaturated fatty acids are associated with microbiota-related 18\u03b2-glycyrrhetinic acid alterations and M2 macrophage polarization in type 1 diabetes mellitus"],"prefix":"10.3389","volume":"17","author":[{"given":"Yifan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Zijian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital of Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjuan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University","place":["Zhuhai, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1515\/jbcpp-2024-0043","article-title":"The underlying causes, treatment options of gut microbiota and food habits in type 2 diabetes mellitus: a narrative review","volume":"35","author":"Adhikary","year":"","journal-title":"J. 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