Establishing a mucosal gut microbial community in vitro using an an artificial simulator

Authors: Liu, Linshu; Firrman, Jenni; TANES, CEYLAN - Children'S Hospital - Philadelphia, Pennsylvania; BITTINGER, KYLE - Children'S Hospital - Philadelphia, Pennsylvania; Thomas-Gahring, Audrey; WU, GARY - University Of Pennsylvania; VAN DEN ABBEEL, PIETER - Prodigest; Tomasula, Peggy

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/7/2018
Publication Date: 7/17/2018
Citation: Liu, L.S., Firrman, J., Tanes, C., Bittinger, K., Thomas-Gahring, A.E., Wu, G.D., Van Den Abbeel, P., Tomasula, P.M. 2018. Establishing a mucosal gut microbial community in vitro using an an artificial simulator. PLoS One. 13(7):1-20. https://doi.org/10.1371/journal.pone.0197692.
DOI: https://doi.org/10.1371/journal.pone.0197692

Interpretive Summary: There is a large community of bacteria that lives in the human colon called the gut microbiota. The gut microbiota is known to affect both human health and disease. However, studying the gut microbiota is difficult because there is limited access to the colon of a human. The twin simulator of the human microbial ecosystem (TWINSHIME) was developed to study the gut microbiota of the colon outside of a human, or in vitro. The TWINSHIME mimics the human colon, and simulates the different parts that make up the colon. In this study, a human donor provided a fecal sample that contained the bacteria that was then grown in the TWINSHIME over a six-week time period. This gut microbiota was evaluated to determine the bacteria that were present and the products or metabolites they were producing. Results of this study provide valuable information regarding the development, structure, and function of the gut microbiota community in humans. These results will be useful to researchers to evaluate the effect of diet on the gut microbial community.

Technical Abstract: The Twin Simulator of the Human Intestinal Microbial Ecosystem (TWINSHIME®) was developed as a system capable of reproducing the conditions of the human gastrointestinal tract, with the purpose of studying the gut microbiota of the colon. The system offers the unique property of representing the ascending, transverse, and descending colon regions with their respective mucosal surfaces. In order to evaluate the ability for the TWINSHIME® to produce a stable gut microbial community representative of the human colon, the system was inoculated with human fecal samples obtained from a single healthy donor and run for a total of six weeks with a consistent nutrition supply. Based on 16S rRNA gene sequencing and short chain fatty acid analysis, it was determined that the system could produce a stable community approximately 10-20 days after inoculation, which remained stable until the end of the experiment. Bioinformatics analysis revealed the formation of unique community structures in the three colon regions, yet these communities were similar to the inoculum. For the first time, differentiation between the luminal and mucosal phases for the three colon regions was studied over the course of a six-week experiment. The unique profile of short chain fatty acid production further demonstrated system stability, but also proved to be an area of marked differences between the in vitro system and in vivo reports. Results of this study demonstrate that it is possible to replicate the community structure and composition of the gut microbiota in vitro. Through implementation of this system, the human gut microbiota can be studied in a dynamic and continuous fashion.