# Microbiota‐gut‐brain axis multi‐organ chip construction and applications in drug evaluation

## TL;DR

This paper reviews how multiorgan chip technology can model the gut-brain axis to study drug effects on neurological disorders.

## Contribution

The paper introduces a novel multiorgan chip platform integrating gut microbiota, gut barrier, blood-brain barrier, and brain for drug evaluation.

## Key findings

- The platform enables the study of neural function, BBB permeability, and microbiota–host interactions.
- It supports pharmacokinetic, pharmacodynamic, and toxicity evaluations for drug screening.
- The technology facilitates cross-organ interaction analysis and targeted drug delivery for neurological diseases.

## Abstract

The theoretical framework of the microbiota‐gut‐brain axis (MGBA) elucidates the influence of gut microbiota (GM) on the central nervous system (CNS) and offers novel approaches for diagnosing and treating neurological disorders. The application of microfluidic organ chips to study this axis represents an innovative methodology, enabling multidisciplinary assessment of drug effects. Bionic microphysiological systems based on these chips establish a groundbreaking paradigm for analyzing cross‐organ interaction mechanisms within the MGBA. This technology facilitates systematic evaluation of pharmacokinetics, host‐microbe coevolution, and neuroendocrine regulation, thereby supporting multimodal cross‐validation in pharmacodynamics, toxicology, and translational medicine. This review summarizes the conceptual foundation and mechanistic insights of the MGBA, highlights recent advances in its constituent Multiorgan components, including gut‐on‐a‐chip, blood‐brain barrier‐on‐a‐chip, and brain‐on‐a‐chip models, alongside multiorgan chip cascade technologies, and underscores their applications in drug evaluation. Additionally, it discusses future challenges and developmental directions for the MGBA multiorgan chip technologies in this field.

Microbiota‐gut‐brain axis multiorgan chip and its applications in drug evaluation. The chip includes essential biological components such as gut microbiota, gut barrier, blood‐brain barrier (BBB), and brain. This integrated platform incorporates neural (blue), endocrine (yellow), immune (pink), and metabolic (green) pathways to investigate the impact of drugs on neural function, BBB permeability, microbiota–host interactions, and gut barrier function. Furthermore, the platform is utilized for mechanism analysis of cross‐organ interactions, drug screening, and preclinical drug research, such as pharmacokinetics, pharmacodynamics, and toxicity evaluation. It also supports the development of microbiota modulation strategies and provides innovative tools for targeted drug delivery for neurological diseases.

Systematically integrating the microbiota‐gut‐brain axis (MGBA) with multiorgan chip technology to construct a research paradigm for elucidating the mechanisms of cross‐organ interactions.Providing a comprehensive elaboration on the technical iterations and current development status of core models, including gut‐on‐a‐chip, blood‐brain barrier‐on‐a‐chip, brain‐on‐a‐chip, as well as multiorgan cascading techniques.Discussing the critical application value of MGBA organ‐on‐a‐chip platforms in drug screening and preclinical drug research, including pharmacokinetic studies, pharmacodynamic profiling, and toxicity evaluation.

Systematically integrating the microbiota‐gut‐brain axis (MGBA) with multiorgan chip technology to construct a research paradigm for elucidating the mechanisms of cross‐organ interactions.

Providing a comprehensive elaboration on the technical iterations and current development status of core models, including gut‐on‐a‐chip, blood‐brain barrier‐on‐a‐chip, brain‐on‐a‐chip, as well as multiorgan cascading techniques.

Discussing the critical application value of MGBA organ‐on‐a‐chip platforms in drug screening and preclinical drug research, including pharmacokinetic studies, pharmacodynamic profiling, and toxicity evaluation.