TY - JOUR
T1 - Poly(D,l-lactide-co-glycolide) particles are metabolised by the gut microbiome and elevate short chain fatty acids
AU - McCoubrey, Laura E.
AU - Ferraro, Fabiana
AU - Seegobin, Nidhi
AU - Verin, Jérémy
AU - Alfassam, Haya A.
AU - Awad, Atheer
AU - Marzorati, Massimo
AU - Verstrepen, Lynn
AU - Ghyselinck, Jonas
AU - De Munck, Julie
AU - De Medts, Jelle
AU - Steppe, Evi
AU - De Vleeschhauwer, Valerie
AU - De Rocker, Gilles
AU - Droesbeke, Alexandra
AU - De Rijck, Melanie
AU - Vanthoor, Sara
AU - Moens, Frédéric
AU - Siepmann, Juergen
AU - Siepmann, Florence
AU - Gaisford, Simon
AU - Orlu, Mine
AU - Basit, Abdul W.
N1 - © 2024 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/
PY - 2024/5
Y1 - 2024/5
N2 - The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs.
AB - The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs.
KW - PLGA
KW - Microbiome medicine
KW - Colonic drug delivery
KW - Nanoparticles and microparticles
KW - Metabolomics
KW - Microbiome sequencing
KW - Spray drying
UR - http://www.scopus.com/inward/record.url?scp=85189000782&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2024.03.039
DO - 10.1016/j.jconrel.2024.03.039
M3 - Article
SN - 0168-3659
VL - 369
SP - 163
EP - 178
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -