Engineering probiotic delivery with nanocarriers: overcoming gastrointestinal barriers and unlocking therapeutic potential: a review

Abstract Probiotics, live microorganisms that confer health benefits when administered in adequate amounts, primarily through gut microbiota modulation and immune system enhancement, encounter significant viability challenges from gastric acidity, bile salts, digestive enzymes, and storage instability, often resulting in survival rates of only 10%–30% during gastrointestinal transit. This review explores nanocarrier-based delivery systems, including liposomes, nanoemulsions, nanogels, and polymeric nanoparticles, as transformative strategies to overcome these barriers and unlock therapeutic potential. Nanocarriers demonstrate superior performance, with in vitro and in vivo studies reporting gastrointestinal survival rates of 70%–95% for encapsulated probiotics compared to free cells. For instance, short-chain fatty acid (SCFA) production increases by up to 2–3 × in 53.3% of analyzed trials, particularly with human-origin strains elevating propionate and butyrate levels to support colonocyte fuel and anti-inflammatory effects. Comparative evaluations highlight platform-specific advantages of nanocarriers: liposomes offer high biocompatibility and mucoadhesion. They enable 50%–80% symptom reduction in dextran sulfate sodium -induced colitis models through co-delivery, such as Bacillus subtilis spores with dexamethasone. Nanogels provide ROS-responsive release. For example, hyaluronic acid-based systems encapsulate probiotics to scavenge reactive oxygen species and suppress cytokines by up to 70%–80% in inflammatory bowel disease (IBD). Polymeric nanoparticles achieve tunable site-specific targeting, and inhibit tumor growth via enhanced Short-chain fatty acids -mediated apoptosis. Despite these advances, challenges persist, including cytotoxicity, potential microbiome disruptions, and regulatory gaps, demanding biocompatible, scalable innovations like good manufacturing practices-compliant processes and longitudinal safety assessments. Ultimately, these findings establish nanocarriers as pivotal links in precision microbiome medicine, integrating biotechnology, nutrition, and oncology to enable targeted, risk-minimized therapies for IBD, colitis, metabolic disorders, and colorectal cancer adjuncts, fostering personalized interventions based on microbial composition and biomarkers or Shannon diversity index.