Organoids, organs-on-chips and other systems, and microbiota

Abstract

The human gut microbiome is considered an organ in its entirety and has been the subject of extensive research due to its role in physiology, metabolism, digestion, and immune regulation. Disequilibria of the normal microbiome have been associated with the development of several gastrointestinal diseases, but the exact underlying interactions are not well understood. Conventional in vivo and in vitro modelling systems fail to faithfully recapitulate the complexity of the human host-gut microbiome, emphasising the requirement for novel systems that provide a platform to study human host-gut microbiome interactions with a more holistic representation of the human in vivo microenvironment. In this review, we outline the progression and applications of new and old modelling systems with particular focus on their ability to model and to study host-microbiome cross-talk.

Clinical translation of microbe‐based therapies: Current clinical landscape and preclinical outlook

“…For drug‐secreting bacteria, it is necessary to understand the microenvironment conditions that dictate pharmacokinetic parameters. Recent work has shown that in vitro preclinical models can be used to recreate interactions within and between the microbiota, human host, and the microenvironment to study complex biological interactions . While these systems are in their infancy, both static and dynamic in vitro models can be used identify and evaluate microbe therapeutics, providing valuable information that can inform formulation approaches.…”

2D- and 3D-Based Intestinal Stem Cell Cultures for Personalized Medicine

“…In addition to the establishment of several specific disease models, organoids can be used for high-throughput drug screens [75]. A variety of organoid-based high-throughput screen systems have been established, such as organoid-on-chip [76,77]. As there is a strong correlation between gene mutation status and the therapeutic response, known as mutation-based drug sensitivity [78], the adoption of the tumor organoids has been used in precise cancer therapy.…”

From organotypic culture to body‐on‐a‐chip: A neuroendocrine perspective

“…Skrede & Westgaard 45 Guerineau et al 78 Barbara et al 84 De Kanter et al 99 Toran-Allerand 16 Navratil et al 79 Petrovic et al 83 De Graaf et al 100 O'Rourke et al 52 Alim et al 80 DeNardi et al 87 Li et al 101 Wray et al 50 Schwerdtfeger et al 96 Tobet et al 70…”

“…They are known to influence tissue physiology and have been suggested to decrease intestinal motility, 97 as well as regulate certain enteric neuronal subtypes 98. Slicing intestines became a useful approach for metabolic and toxicological studies in the 2000s 99. Precision cut intestinal slices 100 (PCIS) were first used to study gut drug metabolism capabilities101 and subsequently to characterise the intestinal response to toxins 102.…”