Recent advances in biofabricated gut models to understand the gut-brain axis in neurological diseases

Abstract

Increasing evidence has accumulated that gut microbiome dysbiosis could be linked to neurological diseases, including both neurodegenerative and psychiatric diseases. With the high prevalence of neurological diseases, there is an urgent need to elucidate the underlying mechanisms between the microbiome, gut, and brain. However, the standardized aniikmal models for these studies have critical disadvantages for their translation into clinical application, such as limited physiological relevance due to interspecies differences and difficulty interpreting causality from complex systemic interactions. Therefore, alternative in vitro gut–brain axis models are highly required to understand their related pathophysiology and set novel therapeutic strategies. In this review, we outline state-of-the-art biofabrication technologies for modeling in vitro human intestines. Existing 3D gut models are categorized according to their topographical and anatomical similarities to the native gut. In addition, we deliberate future research directions to develop more functional in vitro intestinal models to study the gut–brain axis in neurological diseases rather than simply recreating the morphology.

Basic models to advanced systems: harnessing the power of organoids-based microphysiological models of the human brain

“…The GBA is defined as the bidirectional communication pathway between the GI tract, including its commensal microbiome, and the CNS; and it is further recognized as playing a significant role in regulating homeostasis between the two systems, as well as in modulating the immune and endocrine systems [87] (figures 7(A) and (B)). Importantly, the three main communication pathways within the GBA are (1) the immune system, which primarily signals via cytokines; (2) the Vagus nerve, which directly carries neuronal signals; and (3) the neuroendocrine system, which signals via neurotransmitters and GI hormones [88]. Importantly, conventional in vivo GBA models (e.g.…”

“…gnotobiotic mice) have been instrumental in unveiling the GI/microbiological impact on CNS health and disease progression; however, given the known limitations of animal models and the multifactorial nature of CNS diseases, there is a widespread need for highly controllable and complex humanbased pre-clinical in vitro models, such as MOSs, to dissect the convoluted signals within the GBA. While an in-depth review of novel biofabricated gut models for the study of neurological diseases is published elsewhere [87,88]. In this section of this review we focus on reviewing a few of the most recent GBA MPS models.…”