New methods to unveil host-microbe interaction mechanisms along the microbiota-gut-brain-axis

Abstract

Links between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the "microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases. Indeed, assessing these signals, whether induced by microbial metabolites or neuro-immune mediators, could significantly increase our knowledge of the microbiota-gut-brain axis. However, this will require the development of appropriate techniques and potential models. Methods for studying the induced signals originating from the microbiota remain crucial in this field. This review discusses the methods and techniques available for studies of microbiota-gut-brain interactions. We highlight several much-debated elements of these methodologies, including the widely used in vivo and in vitro models, their implications, and perspectives in the field based on a systematic review of PubMed. Applications of various animal models (zebrafish, mouse, canine, rat, rabbit) to microbiota-gut-brain axis research with practical examples of in vitro methods and innovative approaches to studying gut-brain communications are highlighted. In particular, we extensively discuss the potential of "organ-on-a-chip" devices and their applications in this field. Overall, this review sheds light on the most widely used models and methods, guiding researchers in the rational choice of strategies for studies of microbiota-gut-brain interactions.

Keywords: Microbiota-gut-brain; chip; microbiota; model; preclinical.

Figure 1.

PRISMA flowchart, showing literature search.

Figure 2.

Figure 1: a schematic representation of in-vitro, ex-vivo, and in-vivo models in studying microbe-host interactions. (a) microbial culture approach for the analysis of microbe-derived metabolites. (d) advantages and characteristics of zebrafish as an animal model in microbe-host interaction studies of the gut-brain axis. Created with BioRender.com.

Figure 3.

A schematic representation of an organ-on-chip model and the fundamental compartments of a gut-on-chip model. (a) ex-vivo intestinal isolation and technical applications to study cellular features of the intestinal tissue. (b) schematic presentation of 3D organoid culture system and technical potential application to understand microbiota-gut-brain interaction from dog intestine. (c) schematic representation of a gut-on-chip model that mimics intestinal microenvironment. (d) a technical approach is used to evaluate in vitro conditions and the effects of metabolites. Created with BioRender.com.