The human small intestine is a complex and dynamic organ tasked with enzymatic digestion and absorption of nutrients. However, detailed canvassing and characterization of nutrient digestion and bioavailability is limited due to the small intestine’s relative inaccessibility. Numerous in vitro models have been developed to simulate small intestine enzymatic digestion, but few emulate nutrient absorption and none to date incorporate the resident microbiota. Other challenges limiting model efficacy include differential pH and oxygen availability along the length of the small intestine, fluctuations in residence time, and food-dependent host secretion of digestive compounds. Here, we present our work to develop an in vitro fermentation model of the small intestine addressing these challenges. A systematic, stepwise biofidelic model design approach was implemented with initial stages consisting of simulating ileum conditions, including pH and residence time, by utilizing an automated bioreactor system for real-time monitoring and control of fermentation parameters, with incorporation of digestive enzymes and bile acids to enhance degradation of food inputs. Nutrient absorption was simulated by utilizing hollow-fiber columns to emulate passive diffusion, initially optimized using small molecules to mimic dietary digestion byproducts. Validation of the single-stage model with food components representing carbohydrates, protein, and fats, such as starch or whey powder, will be presented. Efforts to design a mock microbial community emulating the small intestine microbiome, including literature searches to identify pertinent organisms and mock community design strategy, will also be presented. These efforts will be the foundation for our long-term goal of simulating all three domains of the small intestine in series with our large intestine fermentation model, jA2COB, creating a six-chambered in vitro fermentation model of the lower gastrointestinal tract. Insight gleaned from this model, alone or in concert with in vivo studies, can inform nutritional strategies to restore and maintain host gut homeostasis.

Development of an in vitro fermentation model of the small intestine

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.