Intestinal in vitro and ex vivo Models to Study Host-Microbiome Interactions and Acute Stressors

Abstract

The gut microbiome is extremely important for maintaining homeostasis with host intestinal epithelial, neuronal, and immune cells and this host-microbe interaction is critical during times of stress or disease. Environmental, nutritional, and cognitive stress are just a few factors known to influence the gut microbiota and are thought to induce microbial dysbiosis. Research on this bidirectional relationship as it pertains to health and disease is extensive and rapidly expanding in both in vivo and in vitro/ex vivo models. However, far less work has been devoted to studying effects of host-microbe interactions on acute stressors and performance, the underlying mechanisms, and the modulatory effects of different stressors on both the host and the microbiome. Additionally, the use of in vitro/ex vivo models to study the gut microbiome and human performance has not been researched extensively nor reviewed. Therefore, this review aims to examine current evidence concerning the current status of in vitro and ex vivo host models, the impact of acute stressors on gut physiology/microbiota as well as potential impacts on human performance and how we can parlay this information for DoD relevance as well as the broader scientific community. Models reviewed include widely utilized intestinal cell models from human and animal models that have been applied in the past for stress or microbiology research as well as ex vivo organ/tissue culture models and new innovative models including organ-on-a-chip and co-culture models.

Keywords: DoD; ex vivo; in vitro; intestine; physiology; stress.

Figure 1

3D enteroids from human and mouse biopsy samples. (A) proliferation stain Edu (green), nuclei (blue) and f-actin (red) in human duodenal organoids. (B) proliferation stain Edu (green), nuclei (blue) and f-actin (red) in murine duodenal organoids. (C) 20X brightfield image of human duodenal organoids. (D) 20X brightfield image of murine duodenal organoids.

Figure 2

Summary of in vitro and ex vivo models including species origin, intestinal region, and most commonly utilized culture methods.