Bifidobacterium animalis subsp. lactis Ca360 Promotes Oral Iron Repletion, Alters the Gut Microbiota, and Regulates Host Metabolism and Inflammatory Status in a Murine Model of Iron Deficiency Anemia Caused by a Low-Iron Diet

<b>Background/Objectives:</b> Iron deficiency anemia (IDA) is a widespread nutritional disorder characterized by impaired iron absorption, inflammation-associated iron restriction, and disrupted iron homeostasis. Increasing evidence suggests that gut microbiota play an important role in iron metabolism; however, the mechanisms underlying probiotic-assisted iron supplementation remain unclear. Our research group previously conducted in vitro fermentation screening experiments and obtained a bacterial strain, <i>B. lactis</i> Ca360, which possesses iron absorption-enhancing activity. <b>Methods:</b> In this study, an IDA mouse model induced by a low-iron diet was used to investigate whether <i>B. lactis</i> Ca360 could synergistically improve iron metabolism when combined with iron supplementation. Mice were treated with FeSO₄ alone or FeSO₄ combined with <i>B. lactis</i> Ca360, and hematological parameters, organ indices, serum iron-related markers, histopathological changes, duodenal iron metabolism-related gene expression, hepatic inflammatory responses, gut microbiota composition, short-chain fatty acid (SCFA) levels, and correlation networks were analyzed. <b>Results:</b> Iron deficiency induced typical anemia phenotypes, multi-organ dysfunction, intestinal iron absorption dysregulation, hepatic inflammation, and gut microbiota dysbiosis. Compared with FeSO₄ alone, the combined intervention more effectively improved hematological parameters, reduced organ indices, restored liver and spleen histological integrity, normalized intestinal iron metabolism-related gene expression, and alleviated hepatic inflammation. In addition, <i>B. lactis</i> Ca360 markedly reshaped gut microbiota composition, enriching SCFA-producing anaerobic genera, including <i>Ruminococcus</i>, <i>Roseburia</i>, <i>Acetatifactor</i>, <i>Intestinimonas</i>, <i>Eubacterium_coprostanoligenes_group_unclassified</i>, and <i>Oscillibacter</i>, accompanied by increased acetate, propionate, and butyrate levels. Spearman correlation analysis further revealed close associations between gut microbiota remodeling, improved iron metabolism, reduced inflammatory status, and recovery of anemia-related phenotypes. <b>Conclusions:</b> Overall, these findings demonstrate that <i>B. lactis</i> Ca360 enhances the efficacy of iron supplementation by modulating SCFA-producing and anti-inflammatory gut microbiota, thereby coordinately regulating intestinal iron absorption, inflammation, and systemic iron homeostasis, supporting probiotic-assisted iron supplementation as a promising nutritional strategy for IDA management.