From Bioreactors to Organoids: Tools for Culturing and Understanding Microbiota.

Emerging evidence on the role of gut microbiota on human health necessitated the investigations on gut microbial composition and functions. The diet, drug and disease are the major factors that influence the gut microbial composition and subsequent changes in gut physiology. The consequences of external factors on gut microbiota leads to immunological and neurological disorders. The in vivo studies and animal models are associated with difficulties such as surgical procedures, differences in animal and human tissue responses and ethical issues. Microbiota culture outside the in vivo systems provides mechanistic insights on the effect of external factors on gut microbiota function. In order to provide more information on gut microbiota, researchers have developed intestinal gut models that allow the culture of microbiota under controlled conditions. The multistage, dynamic in vitro fermenters have been developed to simulate the stomach, intestine and colon conditions to culture microbiota. The co-culture of host and microbiome is difficult in in vitro models due to differences in the culture media and oxygen requirements for both the cultures. Microfluidics based gut on chip models demonstrated co-culture of host and microbiota in separate channels connected by semipermeable membranes. Host-microbiota interactions play an important role in deciphering the mechanisms of microbiota related human diseases. The ex-vivo systems show more resemblance to the host signaling as these systems use the individual's explants or host tissues. This review discusses the design considerations, pros and cons of the existing in vitro, microfluidic and ex-vivo intestinal microbiota culture models. The collective information provided in this review would be helpful to design novel in vitro microbiota culture models or methods.