Exploration (Beijing, China)Sep 10, 2026

Oral probiotic-like drug system that crosses barriers to influence the gut-brain connection for Parkinson’s treatment

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

Updated Sep 11, 2026

Abstract

A probiotic spore-based oral drug delivery system demonstrates multiple-barriers-crossing ability to target both the gut and brain.

Spore coat proteins shed during germination can reassemble into nanoparticles capable of penetrating multiple physiological barriers.
The delivery system crosses the gastrointestinal chemical barrier after oral administration and germinates in the intestine.
Probiotics generated from the spores modulate the gut-brain axis, potentially influencing brain health.
Reassembled nanosystems derived from spore proteins can penetrate intestinal mucus, enterocyte, and blood-brain barriers.
In a mouse model of Parkinson's disease, neurodegeneration and behavioral deficits are alleviated.
This approach may offer a new alternative to traditional single-targeted methods for treating central nervous system diseases.

Simplified

For Parkinson's disease (PD), the development of oral brain-targeted drug delivery is challenging due to various physiological barriers. Besides the brain, the effect of the gut on the microbiome-gut-brain axis should not be ignored. Therefore, developing a gut-brain dual-targeted delivery system with multiple-barriers-crossing ability is meaningful. During the germination of probiotic spores, we find that spore coat proteins (SP) shed from their surface possess excellent characteristics (re-assembling into nanoparticles, multiple-barriers penetration ability, antioxidant property, etc.), offering potential for brain-targeted drug delivery. Inspired by this, we propose a probiotic spore based oral drug delivery system to dual-regulate the gut-brain. After oral administration, the spore system crosses the harsh gastrointestinal chemical barrier. Spores germinate in the intestine into probiotics to modulate the gut-brain axis. Meanwhile, the SP-derived reassembled nanosystems cross multiple barriers (intestinal mucus barrier, enterocyte barrier, blood-brain barrier) to reach brain and further reduce oxidative stress. Notably, neurodegeneration and behavioral deficits are alleviated in PD mice. Such gut-brain dual-regulation strategy emphasizes a comprehensive and promising technique for central nervous system disease treatment, which may be an alternative to traditional single-targeted methods. Furthermore, the probiotic spore-based oral biotherapeutics with multiple-barriers-crossing efficiency provide new insight into other brain diseases.