1 | INTRODUCTION
The gut microbiota is a diverse and complex community of bacteria,
archaea, fungi and viruses. The characteristics of its species
composition and function have garnered great interest of researchers in
recent years. The microbial community is an integral part of the
gastrointestinal tract as it provides the host with an extended set of
metabolic, structural and protective functions (O’Hara & Shanahan,
2006). In recent times, dysbiosis of the gut microbiota has been
associated with a variety of diseases, such as inflammatory bowel
diseases, diabetes, obesity, cancers, and even some behavioral disorders
(Musso et al., 2011; Manichanh et al., 2012; Zhu et al., 2013; Vuong et
al., 2017). It is now accepted that the gut microbiota has a strong
influence on host health.
Due to the complex nature of the host-microbial interaction, it is
difficult to infer specific mechanistic aspects of this interaction
using conventional in vivo models and thus highlights the need for
facile in vitro systems to help understand the complex interactions
between the host and its gut microbiota (de Vos & de Vos, 2017). The
currently available in vitro gut models vary in their complexity (Molly
et al, 1993; Minekus et al., 1999; Makivuokko & Nurminen, 2006; Payne
et al., 2012; Tanner et al., 2014; Moon et al., 2016; Card et al., 2017;
von Martels et al., 2017; Dupont et al., 2019). Batch culture models are
simple closed fermentation systems, that usually operate for less than
two days. In continuous culture models, which might be single or
multi-stage in design, fresh culture medium, supplemental growth factors
or any other additives, are added continuously, while wastes and toxic
byproducts are prevented from accumulating excessively by continuous
dilution of the spent medium with fresh culture medium (Moon et al.,
2016). The addition of fresh medium can be scheduled at specified time
intervals as in the semi-continuous model EnteroMix (Makivuokko &
Nurminen, 2006), or continuously supplied as in the Simulator of the
Human Intestinal Microbial Ecosystem (SHIME) model (Molly et al, 1993).
Some models, such as the TNO Gastro-Intestinal Model TIM1 and TIM2
systems (Minekus et al., 1999), permit simulation of intestinal tract
processes like digestion and absorption. Other models permit
incorporation of intestinal tissues by employing co-culturing techniques
(von Martels et al., 2017). Different gut models have been developed for
in vitro study of complex microbial communities associated with various
physiological and pathological states, or from the digestive tracts of
humans and animals (Tanner et al., 2014; Card et al., 2017).
Since most of the in vitro gut models in existence were designed to
simulate a specific digestive tract or condition, their designs
inherently make it difficult to study different conditions or
applications using the one device. Here we describe the design and
implementation of a modular bioreactor. The novel bioreactor design
serves as a new platform that features unparalleled functional
flexibility for the culturing of mono- and mixed bacterial cultures in
vitro. In particular, the bioreactors can operate either as single
static batch cultures or connected in series to dynamically simulate the
environments of the various segments of the gastrointestinal tract.