Hydrogen Therapy and Lipopolysaccharide Trapping with MgB2@Inulin Gel for Reversing Colitis and Its Associated Psychiatric Complications via the Gut–Brain Axis

Individuals diagnosed with inflammatory bowel disease (IBD) frequently encounter dysbiosis of the intestinal microbiota and are predisposed to psychiatric comorbidities, such as depression and anxiety. The development of oral therapeutics that concurrently attenuate intestinal inflammation, modulate gut microbiota, and ameliorate psychiatric symptoms is imperative for effective IBD management. This study introduced an orally administered Inulin gel incorporating magnesium diboride nanosheets (MgB₂@Inulin gel). The hydrolysis of MgB₂ nanosheets could generate reductive hydrogen gas (H₂), which is critical for scavenging excess reactive oxygen/nitrogen species (RONS), and boron ions that neutralize harmful lipopolysaccharides (LPS). Prebiotic Inulin could effectively protect MgB₂ nanosheets from gastric acid degradation, ensuring their persistence in the intestinal tract, where it modulated the gut microbiota and preserved intestinal barrier integrity. Notably, MgB₂@Inulin gel markedly alleviated anxiety and depressive behaviors in the model of colitis by regulating the gut-brain axis. Thus, this work underscores the pivotal role of the gut-brain axis in the therapeutic approach to IBD and its associated psychiatric manifestations, proposing a straightforward, safe, and efficacious oral hydrogen treatment strategy for IBD and concurrent mental health disorders.