Advanced science (Weinheim, Baden-Wurttemberg, Germany)Jul 20, 2026

Oral Apremilast Nanotherapy Covered with β-Glucan Changes Gut Bacteria Linked to Imbalance and Reduces Anxiety, Depression, and Brain-Related Symptoms in Ulcerative Colitis

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 21, 2026

Abstract

Oral gastroprotective βG@Apr-WPG nanomedicines significantly improved therapeutic efficacy in treating inflammatory bowel disease (IBD) and associated psychiatric disorders.

These nanomedicines modulate the microbiota-gut-brain axis, which is important for managing IBD and related anxiety and depression.
Administration of βG@Apr-WPG nanomedicines enhanced drug solubility and enabled sustained release within the inflamed colon.
The nanomedicines restored gut barrier integrity and reduced histopathological damage compared to free apremilast.
Systemic inflammation and neuroinflammation were markedly suppressed with βG@Apr-WPG nanomedicine treatment.
Anxiety- and depression-like symptoms, along with cognitive deficits in colitis-induced mice, were improved by these nanomedicines.

Simplified

Oral nanomedicines that modulate gut microbiota and gut-brain interactions are crucial for effectively treating inflammatory bowel disease (IBD) and associated psychiatric disorders, such as anxiety and depression. However, the underlying causes of psychiatric disorders in patients with IBD remain unclear, and effective treatment strategies have yet to be established. Herein, we developed oral gastroprotective βG@Apr-WPG NMs (β-glucan armored apremilast encapsulating tryptophan-poly(lactic-co-glycolic acid)-glutathione nanomicelles). This system effectively treats IBD and associated anxiety/depression by modulating the microbiota-gut-brain axis. βG@Apr-WPG NMs demonstrated gastroprotection enhances retention, and enables sustained release within the inflamed colon, enhances drug solubility, and inflammation-responsive apremilast release significantly improving oral therapeutic efficacy. Oral βG@Apr-WPG NMs administration outperformed free apremilast by restoring gut barrier integrity, reducing histopathological damage, and modulating microbial dysbiosis. Systemic inflammation and neuroinflammation were markedly suppressed. Notably, the βG@Apr-WPG NMs ameliorated anxiety- and depression-like symptoms, as well as cognitive deficits in colitis-induced mice, highlighting its therapeutic impact beyond the gut. Addressing reduced efficacy of conventional therapies, this multifunctional βG@Apr-WPG NMs platform offers safe, simple, and highly efficient therapeutic strategy integrating targets intestinal inflammation, microbiota-gut-brain axis modulation, in the pathogenesis of IBD with comorbid neuropsychiatric disorders with confirmed safety.