{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:05:08Z","timestamp":1789621508264,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Immunosuppression induced by chemotherapeutic agents such as cyclophosphamide (CTX) is frequently associated with gut microbiota dysbiosis.\n                      <jats:italic>Sanghuangporus sanghuang<\/jats:italic>\n                      polysaccharide (SSP1) possesses immunomodulatory potential; however, its effects on mucosal immunity and the gut microbiota remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we investigated the immunomodulatory activity of SSP1 in CTX-induced immunosuppressed mice. Mice were treated with different doses of SSP1 orally. We assessed immune organ indices, histopathology of immune organs and colon, oxidative stress, splenocyte proliferation, T-cell subsets, and cytokine production. Additionally, 16S rRNA sequencing was used to analyze gut microbiota composition; targeted analysis was performed on short-chain fatty acids (SCFAs); and untargeted metabolomics was used to evaluate metabolic profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Oral administration of SSP1 significantly alleviated immunosuppression in a dose-dependent manner, with the high dose (SSP1-H) showing the most pronounced effects. This was evidenced by restored body weight, increased spleen and thymus indices, improved histopathology, and attenuated oxidative stress. SSP1 promoted splenocyte proliferation, elevated CD45\n                      <jats:sup>+<\/jats:sup>\n                      leukocytes and CD3\n                      <jats:sup>+<\/jats:sup>\n                      T cells, enhanced IL-2 and IL-4 production, suppressed IFN-\u03b3 secretion, and inhibited LPS-induced pro-inflammatory cytokines (IL-1\u03b2, IL-6, TNF-\u03b1). Gut microbiota analysis revealed that SSP1-H increased \u03b1-diversity, enriched beneficial bacteria (\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      and\n                      <jats:italic>Odoribacter<\/jats:italic>\n                      ), and elevated SCFAs (acetate, propionate, and valerate). Correlation analysis showed SCFA levels were positively correlated with antioxidant markers, T-cell subsets, and IL-10, and negatively correlated with pro-inflammatory cytokines. Untargeted metabolomics further indicated that SSP1-H regulated serine, threonine, and taurine metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings suggest that high-dose SSP1 treatment was associated with coordinated changes in gut microbiota composition, SCFA production, and immune parameters, supporting a potential microbiota\u2013metabolism\u2013immune axis. This implies that SSP1\u2019s protection against CTX-induced immunosuppression is associated with regulating immune cell functions and reshaping the gut microbiota to enhance SCFA production, providing new insights into the immunoregulatory mechanisms of Sanghuang polysaccharides and highlighting their potential as functional food ingredients or immune adjuvants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1931873","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:50:15Z","timestamp":1789620615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunomodulatory effects of Sanghuangporus sanghuang polysaccharide SSP1 in cyclophosphamide-induced immunosuppressed mice: associations with gut microbiota, short-chain fatty acids, and metabolic 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