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Cutting-Edge iPSC-Based Approaches in Studying Host-Microbe Interactions in Neuropsychiatric Disorders - PubMed

  • ️Mon Jan 01 2024

Review

Cutting-Edge iPSC-Based Approaches in Studying Host-Microbe Interactions in Neuropsychiatric Disorders

Marija Mihailovich et al. Int J Mol Sci. 2024.

Abstract

Gut microbiota (GM), together with its metabolites (such as SCFA, tryptophan, dopamine, GABA, etc.), plays an important role in the functioning of the central nervous system. Various neurological and psychiatric disorders are associated with changes in the composition of GM and their metabolites, which puts them in the foreground as a potential adjuvant therapy. However, the molecular mechanisms behind this relationship are not clear enough. Therefore, before considering beneficial microbes and/or their metabolites as potential therapeutics for brain disorders, the mechanisms underlying microbiota-host interactions must be identified and characterized in detail. In this review, we summarize the current knowledge of GM alterations observed in prevalent neurological and psychiatric disorders, multiple sclerosis, major depressive disorder, Alzheimer's disease, and autism spectrum disorders, together with experimental evidence of their potential to improve patients' quality of life. We further discuss the main obstacles in the study of GM-host interactions and describe the state-of-the-art solution and trends in this field, namely "culturomics" which enables the culture and identification of novel bacteria that inhabit the human gut, and models of the gut and blood-brain barrier as well as the gut-brain axis based on induced pluripotent stem cells (iPSCs) and iPSC derivatives, thus pursuing a personalized medicine agenda for neuropsychiatric disorders.

Keywords: dysbiosis; gut–brain axis; iPSC-based gut barrier, blood–brain barrier and gut–brain axis models; microbiota; neuroinflammation; probiotics; targeted culturomics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 2
Figure 2

An overview of the state-of-the-art models used to study GM–host interactions. Schematic representations of the following models are presented: (A) gut barrier (intestine-on-a-chip, Intestine Chip) [153]; (B) static BBB model composed of astrocytes, pericytes, brain microvascular endothelial cells (HBMECs) and neurons [145]; (C) human iPSC-derived BBB-on-a-Chip model composed of induced BMECs (iBMECs), induced astrocytes (iAstrocytes), and iNeurons [155]; (D) “The Substantia Nigra Brain-Chip”, composed of human iBMECs, pericytes, astrocytes, microglia, and induced dopaminergic neurons [156]; (E) AD-BBB model, in which the brain side is composed of human neural progenitor ReN cells, wild type (ReN-WT) or expressing familial AD-related APP and APP/PSEN1 mutations (ReN-AD models), whereas the BBB side is composed of the brain microvascular endothelial cell line hCMEC/D3 [158]; (F) GBA-on-a-Chip model composed of the gut barrier (Caco-2 cells) and the BBB barrier (populated with murine brain endothelial cell line bEnd.3 or hBMECs) [157].

Figure 1
Figure 1

Bidirectional communication network between the gut and brain depicting cross-talk between two semi-permeable barriers: the intestinal barrier and blood–brain barrier; ENS—enteric nervous system.

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