Institute of Biochemical Engineering, Technische Universität Braunschweig, Braunschweig, Germany.
Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, Germany.
Biotechnol Bioeng. 2024 Mar;121(3):1118-1143. doi: 10.1002/bit.28636. Epub 2023 Dec 27.
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 ). 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.
介绍了一种新型生物反应器,用于模拟人体结肠条件进行肠道微生物群落的体外培养。PEristaltic 混合管状生物反应器(PETR)采用模块化设计,周期性揉捏以模拟肠道蠕动。从生物工艺工程师的角度介绍并描述了该反应器,并讨论了其模拟结肠条件的能力。PETR 提供生理温度和适当的厌氧条件,模拟肠道蠕动,平均停留时间为 32.8 ± 0.8 h,与成人结肠相当。单管设计可实现从 5.5 到 7.0 的恒定和纵向 pH 梯度。使用含有高分子量聚乙二醇的透析液,集成的透析系统可有效吸收短链脂肪酸(高达 60%)和水(平均 850 mL/d)。培养典型的肠道细菌(动物双歧杆菌)以证明其用于控制微生物群落培养的适用性。PETR 的独特之处在于在单管设计中结合了整个结肠的模拟、蠕动混合、透析水和代谢物吸收以及渐进的 pH 梯度。PETR 是在体外精确复制结肠条件的又一步骤,可用于可靠和可重复的微生物群落研究,例如研究食物化合物、益生元和益生菌的影响,或肠道病原体感染的发展和治疗,但也可用于进一步的医疗应用,如药物输送研究或研究药物对微生物群落的影响及其降解。