Gastrointestinal-inert prebiotic micro-composites improve the growth and community diversity of mucosal-associated bacteria

• Published in: Journal of controlled release 2024-11, Vol.375, p.495-512
• Main Authors: Ta, Linh P., Corrigan, Sarah, Tselepis, Chris, Iqbal, Tariq H, Ludwig, Christian, Horniblow, Richard D.
• Format: Article
• Language: English
• Subjects: Biopolymer hydrogel; Gastrointestinal resistance; Microbiome; Microcomposite; Prebiotic
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2024.09.021

The process of microencapsulation and the development of microparticle-based drug formulations have gained increased pharmaceutical interest, particularly for drug delivery and bacterial-encapsulation purposes for probiotic delivery. Existing studies have examined microcomposite (MC) responses to gastrointestinal (GI) conditions with the aim of controlling disintegration, and thus release, across the small and large bowel. However, the delivery of MCs which remain intact, without degrading, could act as bacterial growth scaffolds or materials providing a prebiotic support, conferring potentially beneficial GI health properties. This present study employs prilling as a method to produce a portfolio of MCs using a variety of biopolymers (alginate, chitosan, pectin and gellan gum) with a range of MC diameters and density compositions. Fluorescent probes are co-encapsulated within each MC to enable flow-cytometry directed release profile assessments following exposure to chemical simulated gastric and intestinal digestion conditions. We observe that MC size, gel-strength, density, and biopolymer material all influence response to gastric and intestinal conditions. Gellan gum (GG) MCs demonstrated complete resistance to disintegration throughout GI-simulation in the stomach and small intestine. Considering these MCs could reach the colon intact, we then examined how such MCs, doped with prebiotic growth supporting carboxymethyl cellulose (CMC) polymers, could impact microbial communities using a bioreactor model of the colonic microbiome. Following supplementation with GGCMC MCs, mucosal bacterial diversity (using 16 s rRNA sequencing and Shannon entropy and observed feature diversity metrics) and taxonomic composition changes were observed. Concentrations of short chain fatty acid (SCFA) metabolites were also found to be altered. This is the first study to comprehensivelyexamine how MC physicochemistry can be manipulated to tailor MCs to have the desired GI release performance and subsequently, how GI-resistant MCs could have influential microbial altering properties and be adopted in novel prebiotic strategies. [Display omitted] •The physicochemistry of hydrogel microcomposites (MCs) are manipulated to tailor gastrointestinal (GI) release.•Commonly used MC formulation materials significantly impacted the intestinal microbiota.•MCs that are inert to GI degradation act as prebiotics.•Carboxymethylcellulose/Gellan Gum MCs improve the growth of beneficial intesti