Title : Formulation of odoribacter splanchnicus for oral colon delivery: Manufacturing and in vitro evaluation
Abstract:
Gut microbiome is gaining increasing interest as an innovative field of research mainly because of the growing evidence on implications of its alteration in a variety of diseases, ranging from intestinal to cardiovascular and brain ones. Therefore, identification and replenishment of specific bacterial strains, whose depletion is associated with a certain disease could provide an interesting therapeutic option. Odoribacter splanchnicus, an anaerobic member of the human intestinal microbiota, has been reported to establish a beneficial interaction with the host, and a decrease in its abundance has been related to a wide range of pathologies, such as inflammatory bowel disease (IBD), non-alcoholic fatty liver and cystic fibrosis. Colonization of mice with O. splanchnicus led to an increase in Foxp3+/RORγt+ regulatory T cells, induction of interleukin-(IL) 10 and production of short-chain fatty acids, all of which resulted in limiting colitis in the mouse model. Given the anti-inflammatory properties of O. splanchnicus and its possible therapeutic use for IBD, colon delivery would be highly beneficial and protect the bacteria from the hostile upper gastrointestinal environment. Based on these premises, the aim of the present work was to formulate pure culture of O. splanchnicus 57 for colonic release according to a time-dependent delivery strategy. In particular, an inner swellable/erodible hydrophilic polymer layer and an outer enteric coating were applied by powder-layering and spray-coating techniques, respectively. Powder-layering was attempted due to limited working temperatures, amount of water in use and processing time. The bacterial viability was assessed after freeze-drying, tableting, powder-layering and spray-coating manufacturing steps. Furthermore, the anti-inflammatory properties of the bacterial strain were assessed before and after processing. The study pointed out that, while freeze-drying did not affect bacterial viability, tableting and coating processes were more stressful. However, the strain was importantly found to maintain its ability to attenuate LPS induced IL-8 release from HT-29 cell line.
Audience Take Away:
Scientists interested in leveraging the gut microbiota as a therapeutic target or a therapeutic strategy will learn that release of probiotics to the colon may be more advantageous than to the proximal gastrointestinal tract, and an anaerobic bacterial strain can be formulated and processed for oral delivery provided that suitable technologies and operating conditions are set up.
