PETR: A novel peristaltic mixed tubular bioreactor simulating human colonic conditions.

Abstract

A novel bioreactor simulating human colonic conditions for in vitro cultivation of intestinal microbiota is presented. The PEristaltic mixed Tubular bioReactor (PETR) is modular designed and periodically kneaded to simulate intestinal peristalsis. The reactor is introduced, characterized from a bioprocess engineer's perspective and discussed in its ability to mimic colon conditions. PETR provides physiological temperature and appropriate anaerobic conditions, simulates intestinal peristalsis, and has a mean residence time of 32.8 ± 0.8 h comparable to the adult human colon. The single-tube design enables a time-constant and longitudinally progressive pH gradient from 5.5 to 7.0. Using a dialysis liquid containing high molecular weight polyethylene glycol, the integrated dialysis system efficiently absorbs short chain fatty acids (up to 60%) and water (on average 850 mL d-1 ). Cultivation of a typical gut bacterium (Bifidobacterium animalis) was performed to demonstrate the applicability for controlled microbiota cultivation. PETR is unique in combining simulation of the entire colon, peristaltic mixing, dialytic water and metabolite absorption, and a progressive pH gradient in a single-tube design. PETR is a further step to precise replication of colonic conditions in vitro for reliable and reproducible microbiota research, such as studying the effect of food compounds, prebiotics or probiotics, or the development and treatment of infections with enteric pathogens, but also for further medical applications such as drug delivery studies or to study the effect of drugs on and their degradation by the microbiota.