Gut Microbiota and Health

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The human gastrointestinal tract harbors a large and complex consortium of microorganisms commonly referred to as the intestinal microbiota. There is a complex relationship between the gut microbiota, diet and host in the intestine. We have developed different in vitro and in vivo strategies to elucidate mechanisms or functions of dietary compounds on the gut microbiota, as well as human health and physiology. In addition to the microbial composition of the gut, our research focuses on the modulation of functionality and combines in vitro models and in vivo investigations within a coherent strategy.

In vitro gut modeling has gained momentum in recent years as a powerful strategy to isolate and investigate factors of the gut microbiota and evaluate specific effects on host cells.

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 The main challenge of in vitro models mimicking the human colonic fermentation is to reproduce high cell density and diversity, microbial networks and complex cross-feeding mechanisms of the intestinal microbiota. As an application of our long term research on high cell density immobilized cell fermentations, we developed several continuous intestinal fermentation models inoculated with immobilized fecal microbiota. The models feature anaerobic continuous-flow culture, compositional and metabolic stability, sessile and planktonic growth, high cell density, microbial diversity and balance akin to donor’s fecal materials.

Models based on our novel PolyFermS platform were developed and validated for human and swine gut microbiota. We developed various configurations for PolyFermS models that can be flexibly expanded to accurately compare different treatments in experimental blocks. PolyFermS is particularly well suited for parallel screening and mechanistic investigations of gut microbiota factors. Intestinal models have been developed to mimic the gut microbiota of healthy hosts (from infant to the elderly), as well as to investigate nutritional factors such as pro- and pre-biotics, microelements (iron and selenium), energy of the diet, nucleotides, etc. Furthermore, models of infected (Salmonella, Clostridium difficile, Listeria) and dysbiotic microbiota (such as IBD microbiota) are being developed. For this research, we use advanced microbiological, molecular (quantitative PCR, next generation sequencing, transcriptomics) and biochemical methods to monitor composition and activity of the gut microbiota. Particular attention is paid to cultivation techniques for strict anaerobes. Samples from ex vivo models of the human intestinal are also tested on different cellular models to investigate in vitro interactions between the gut microbiota and host cells.

Relevant strategies combining in vitro modeling and in vivo investigations are used to study the complex effects of dietary factors, environmental conditions and other interventions on the gut microbiota, gut health, and host physiology at different scales. This type of holistic approach helps clarify the roles and mechanisms of gut microbiota in healthy and diseased subjects, and provides the knowledge required to translate research results to medical and dietary applications.

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