Novel methods for lyophilized kefir-loaded self-nanoemulsifying delivery system of caraway oil and licorice extract on cognitive function via the microbiota-gut-brain axis

Abstract

Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut-brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. The present invention comprises lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract. Daily administration of lyophilized milk kefir loaded with SNESNS restores normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration, leading to significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut-brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalizes the disease activity index, alleviates histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and alleviation of triggered inflammatory factors and oxidative stress levels.

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