Mulberry-derived postbiotics alleviate LPS-induced intestinal inflammation and modulate gut microbiota dysbiosis

Mulberry-derived postbiotics (MDP) have demonstrated promising bioactive properties, including antioxidant and anti-inflammatory effects; however, their specific role in modulating gut inflammation and microbiota composition remains underexplored. Given the growing interest in functional food ingredients for gut health and managing inflammatory disorders, this study aims to evaluate the effects of MDP in alleviating intestinal inflammation and altering the gut microbiota in an LPS-induced mouse model of systemic inflammation. MDP administration significantly mitigated LPS-induced pathological changes in the intestine, liver, spleen, and kidneys, thereby improving systemic health and immune function. Histological analysis revealed reduced inflammation and tissue damage in the intestinal epithelium, supporting the potential of MDP to improve gut barrier integrity. An antioxidant assay revealed that MDP decreased the malonaldehyde (MDA) levels and increased the enzymatic activities of CAT, SOD, and GSH in response to LPS administration, indicating enhanced cellular antioxidant defenses. Inflammatory cytokine analysis showed that MDP downregulated proinflammatory markers such as <i>TNF-α</i>, <i>IL-1β</i>, <i>IL-6</i>, <i>MYD88</i>, <i>Nrf2 COX-2</i>, and <i>HO1</i>, while upregulating <i>TLR4</i>, resulting in potential anti-inflammatory effects by modulating the TLR4-NF-κb pathway. Moreover, MDP promoted beneficial alterations in gut microbiota composition by increasing the abundance of <i>Firmicutes</i> and <i>Bacteroidetes</i>, which are linked to gut health and inflammation regulation. The changes in gut microbiota composition suggest a potential mechanism by which MDP may help restore gut homeostasis and reduce systemic inflammation. These findings suggest that MDP may serve as promising functional food ingredients that support immune health, reduce inflammation, and promote gut microbiota balance, offering potential applications in fortified foods and nutraceuticals aimed at mitigating inflammatory and metabolic disorders.