AUTHOR=Wang Hui , Wang Qing , Chen Jingjing , Chen Cunrong 

TITLE=Association Among the Gut Microbiome, the Serum Metabolomic Profile and RNA m6A Methylation in Sepsis-Associated Encephalopathy

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.859727

DOI=10.3389/fgene.2022.859727

ISSN=1664-8021

ABSTRACT=<p><bold>Objective:</bold> To investigate the relationship among the gut microbiome, serum metabolomic profile and RNA m6A methylation in patients with sepsis-associated encephalopathy (SAE), 16S rDNA technology, metabolomics and gene expression validation were applied.</p><p><bold>Methods:</bold> Serum and feces were collected from patients with and without (SAE group and non-SAE group, respectively, <italic>n</italic> = 20). The expression of serum markers and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and blood clinical indicators were detected using a double antibody sandwich immunochemiluminescence method. The expression of RNA m<sup>6</sup>A regulator were checked by Q-RTPCR. The gut microbiome was analyzed by 16S rDNA sequencing and the metabolite profile was revealed by liquid chromatography-mass spectrometry (LC-MS/MS).</p><p><bold>Results:</bold> In the SAE group, the IL-6, ICAM-5 and METTL3 levels were significantly more than those in the non-SAE group, while the FTO levels were significantly decreased in the SAE group. The diversity was decreased in the SAE gut microbiome, as characterized by a profound increase in commensals of the <italic>Acinetobacter</italic>, <italic>Methanobrevibacter</italic>, and <italic>Syner-01 genera</italic>, a decrease in [<italic>Eubacterium</italic>]_<italic>hallii</italic>_group, while depletion of opportunistic organisms of the <italic>Anaerofilum</italic>, <italic>Catenibacterium</italic>, and <italic>Senegalimassilia</italic> genera were observed in both groups. The abundance of <italic>Acinetobacter</italic> was positively correlated with the expression of METTL3. The changes between the intestinal flora and the metabolite profile showed a significant correlation. <italic>Sphingorhabdus</italic> was negatively correlated with 2-ketobutyric acid, 9-decenoic acid, and <sc>l</sc>-leucine, and positively correlated with Glycyl-Valine <italic>[Eubacterium]_hallii</italic>_group was positively correlated with 2-methoxy-3-methylpyazine, acetaminophen, and synephrine acetonide.</p><p><bold>Conclusion:</bold> The gut microbiota diversity was decreased. The serum metabolites and expression of RNA m6A regulators in PBMC were significantly changed in the SAE group compared to the non-SAE group. The results revealed that serum and fecal biomarkers could be used for SAE screening.</p>