Fermented <em>&amp;nbsp;Astragalus Radix</em> &amp;nbsp;improve immune function and repair the intestinal mucosal injury in a cyclophosphamide-induced mouse model

Existing studies have shown that probiotic fermentation can enhance the pharmacological activity of Chinese herbal medicines.<em>&nbsp;Astragalus Radix</em><strong>&nbsp;</strong>(AR), a medicinal and edible herb, has rarely been reported regarding its fermentation. In this study, <em>Lactobacillus rhamnosus </em>GG (LGG) was used to ferment AR. By integrating sensory analysis, untargeted metabolomics, and evaluation of immune function and intestinal barrier integrity, we aimed to link fermentation-driven chemical remodeling with enhanced bioactivity. The results indicated that in fermented AR (FAR), the total flavonoid content increased by 23.5% (<em>P &lt; </em>0.05). Metabolomics analysis revealed that 208 compounds were significantly up-regulated and 485 compounds were significantly down-regulated in FAR compared with AR (<em>P &lt; </em>0.05), leading to significant differences in flavor between FAR and AR. Subsequently, we evaluated the intervention effects of AR and FAR in cyclophosphamide-induced immunosuppressed mice. AR and FAR significantly restored the immune organ indices, increased blood cell counts, and elevated immunoglobulin levels. Specifically, FAR increased WBC, PLT, and LYMPH counts by 147.48%, 55.76%, and 149.55%, and IgA, IgG, and IgM levels by 37.15%, 33.88%, and 45.96%, respectively (compared with the CTX group, <em>P &lt; </em>0.05). FAR significantly repaired the intestinal barrier, increasing the expression of&nbsp;ZO-1, occludin, and claudin-1&nbsp;across the jejunum and colon compared to the CTX group (<em>P &lt; </em>0.05), with efficacy superior to AR. Furthermore, FAR suppressed intestinal inflammation by inhibiting the&nbsp;NF-κB pathway, effectively&nbsp;restoring the phosphorylation levels of p-P65 and p-IκBα&nbsp;to normal baseline values. In addtion, FAR reshaped the gut microbiota composition by increasing microbial richness and selectively enriching SCFA-producing and beneficial genera, such as&nbsp;unclassified&nbsp;<em>Lachnospiraceae</em>, <em>Blautia </em>and <em>Muribaculum</em>, thereby restoring the microecological balance disrupted by CTX.