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Implementation of a dynamic in vitro gastrointestinal model (SIMGI) for studying the composition and /or metabolic activities of the human gut microbiota

Authors: Barroso, Elvira; Martínez-Cuesta, M. Carmen; Cueva, Carolina; Peláez, Carmen; Requena, Teresa;

Implementation of a dynamic in vitro gastrointestinal model (SIMGI) for studying the composition and /or metabolic activities of the human gut microbiota

Abstract

[Introduction]: The human gut microbiota is a metabolic organ that harbours a highly complex microbial ecosystem (mainly anaerobes), with the largest community residing in the colon. Indeed, the human colon microbiota constitutes a dynamic and high dense ecosystem that comprises around 500-1000 microbial species (typically 10(11)-10(12) microbes/mL of luminal colon content). This microbial ecosystem serves numerous important functions for human host health, including the maintenance of intestinal homeostasis. Several factors such as diet, genetic background and immune status affect the composition of the microbiota. Today, much attention is paid to the role of gut microbiota in host energy homeostasis and metabolic functions. Moreover, it is now recognized that the gut microbiota plays an even more important role in maintaining human health than previously thought. When studying the community composition and/or metabolic activities of the human gut microbiota, and despite the physiological relevance, in vivo studies are related with some drawbacks (endpoints measurements), thereby limiting the dynamic monitoring of the different parameters. Additionally, difficult sampling and ethical considerations have hindered study of the structure of the normal gut microbiota and its metabolic activities in different parts of the large bowel, and thus most of the investigations have been done on fecal material. To overcome these troubles, diverse in vitro gut models have been developed in order to unravel gut microbial composition and/or metabolic activities taking into account distinct physiological conditions. The complexity of these in vitro gut models is diverse, ranging from rather static fecal incubations without pH control to more complex continuous models involving one or multiple connected, pH-controlled vessels representing different parts of the human colon or in vitro gastrointestinal system models. Due to these limitations, we aimed to develop a dynamic in vitro gastrointestinal model (SIMGI) that closely mimics the physiological processes of the gastrointestinal tract in vivo and the establishment of either a normal gut microbiota or a microbial community under dysbiosis conditions. This will allow us to unravel the mechanisms underlying microbiota imbalances linked to losses of intestinal health and development of some diseases.

[Results and Discussion]: The main feature of this innovative gastrointestinal model (SIMGI) lies in the possibility of simulate interdependent functions of digestion and colonic fermentation in a continuous mode; furthermore, the stomach is comprised of two glass modules with flexible internal walls and in which the gastric content is mix by peristaltic movements. In this regard, this model represents the most advanced approach thus far at simulating interdependent physiological functions within the stomach lumen, small and large intestine. Briefly, the SIMGI comprises five compartments (units) simulating the stomach, small intestine and ascending, transverse and descending colon respectively, operating in a sequential batch mode (computer-driven). Units 1 and 2 simulate the process of ingestion and digestion occurring in the stomach and small intestine and in which many different parameters of the human digestive system can be simulated (temperature, pH, flow of saliva, gastric- and pancreatic juice including digestive enzymes, and bile, peristalsis and transit times). The other 3 units represent the ascending, tranverse and descending regions of the large intestine, which facilitates the spatial, temporal, nutritional and physicochemical properties of the gut microbiota. Careful control of the environmental parameters in these units allows obtaining complex and stable microbial communities which are highly similar in both structure and function to the microbial community in the different regions of the human colon. A stabilization period of three weeks and a two-weeks basal period are followed by treatment and wash-out stages. This multi-stage continuous gastrointestinal system (SIMGI) is therefore a valuable tool for studying the effects of specific variables on the structure and functionality of the gut microbiota.

Resumen del trabajo presentado al European Network For Gastrointestinal Health Research celebrado en Valencia (España) del 18 al 20 de septiembre de 2013.

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selected citations
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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