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Review
. 2022 Aug 4;11(8):1521.
doi: 10.3390/antiox11081521.

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

Peizan Huang  1   2 , Min Liu  1 , Jing Zhang  1   3 , Xiang Zhong  4 , Chunlong Zhong  1
Affiliations
Review

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

Peizan Huang et al. Antioxidants (Basel). .

Abstract

The brain-gut axis (BGA) is an important bidirectional communication pathway for the development, progress and interaction of many diseases between the brain and gut, but the mechanisms remain unclear, especially the post-transcriptional regulation of BGA after traumatic brain injury (TBI). RNA methylation is one of the most important modifications in post-transcriptional regulation. N6-methyladenosine (m6A), as the most abundant post-transcriptional modification of mRNA in eukaryotes, has recently been identified and characterized in both the brain and gut. The purpose of this review is to describe the pathophysiological changes in BGA after TBI, and then investigate the post-transcriptional bidirectional regulation mechanisms of TBI-induced BGA dysfunction. Here, we mainly focus on the characteristics of m6A RNA methylation in the post-TBI BGA, highlight the possible regulatory mechanisms of m6A modification in TBI-induced BGA dysfunction, and finally discuss the outcome of considering m6A as a therapeutic target to improve the recovery of the brain and gut dysfunction caused by TBI.

Keywords: brain-gut axis; m6A RNA modification; traumatic brain injury.

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Conflict of interest statement

The authors declare that they have no conflict of interest. There are no competing interest of any nature to report. This research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the 3 pathways (neural, neuroendocrine and immune) that constitute the brain–gut axis. (1). Neural pathway: the brain regulates gut function mainly through ANS, while the gut microbiome exerts a feedback effect on the brain. (2). Neuroendocrine pathway: stimulation of the brain is transmitted to the gut via the HPA axis, while the gut microbiome influences the brain by affecting the production of immune mediators to activate the HPA axis. (3). Immune pathway: the brain causes gut dysfunction via releasing proinflammatory cytokines to recruit other immune cells, while the gut microbiome disrupts BBB integrity by downregulating TJs expression.
Figure 2
Figure 2
Diagrammatic representation of the gut dysbiosis leads to the development of neurodegenerative diseases and their potential mechanisms through activation of inflammatory pathways.
Figure 3
Figure 3
TBI caused dysbiosis through the BGA and its negative feedback mechanism.
Figure 4
Figure 4
The expressions of cleaved caspase3 in colonic tissue of YTHDF1-knockout mice is significantly downregulated after TBI compared to WT mouses. * p < 0.05.
Figure 5
Figure 5
Schematic diagram of the methyltransferase complex: The components and their interactions.
Figure 6
Figure 6
Schematic diagram of the process of FTO demethylates m6A.
Figure 7
Figure 7
The role of m6A modification in the CNS.
Figure 8
Figure 8
The possible pathways of m6A regulating the pathological process of BGA after TBI: TBI causes the downregulation of m6A, which is involved in TBI-induced BGA disfunction via METTL14/TINCR/NLRP3, METLL3/miR-873-5p/Keap1/Nrf2 signalling, and FTO/Caveolin-1/MMP2/9 pathways.
See this image and copyright information in PMC

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