AUTHOR=Zhou Qi , Tao Xufeng , Guo Fangyue , Zhu Yutong , Wu Yu , Xiang Hong , Shang Dong 

TITLE=The crosstalk between microbiota and metabolites in AP mice: an analysis based on metagenomics and untargeted metabolomics

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1134321

DOI=10.3389/fcimb.2023.1134321

ISSN=2235-2988

ABSTRACT=<sec><title>Background and purpose</title><p>Microbiome dysfunction is known to aggravate acute pancreatitis (AP); however, the relationship between this dysfunction and metabolite alterations is not fully understood. This study explored the crosstalk between the microbiome and metabolites in AP mice.</p></sec><sec><title>Methods</title><p>Experimental AP models were established by injecting C57/BL mice with seven doses of cerulein and one dose of lipopolysaccharide (LPS). Metagenomics and untargeted metabolomics were used to identify systemic disturbances in the microbiome and metabolites, respectively, during the progression of AP.</p></sec><sec><title>Results</title><p>The gut microbiome of AP mice primarily included Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, and “core microbiota” characterized by an increase in Proteobacteria and a decrease in Actinobacteria. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that significantly different microbes were involved in several signaling networks. Untargeted metabolomics identified 872 metabolites, of which lipids and lipid-like molecules were the most impacted. An integrated analysis of metagenomics and metabolomics indicated that acetate kinase (<italic>ackA</italic>) gene expression was associated with various gut microbiota, including <italic>Alistipes</italic>, <italic>Butyricimonas</italic>, and <italic>Lactobacillus</italic>, and was strongly correlated with the metabolite daphnoretin. The functional gene, <italic>O</italic>-acetyl-L-serine sulfhydrylase (<italic>cysK</italic>), was associated with <italic>Alistipes</italic>, <italic>Jeotgalicoccus</italic>, and <italic>Lactobacillus</italic>, and linked to bufalin and phlorobenzophenone metabolite production.</p></sec><sec><title>Conclusion</title><p>This study identified the relationship between the gut microbiome and metabolite levels during AP, especially the <italic>Lactobacillus-, Alistipes-</italic>, and <italic>Butyricimonas</italic>-associated functional genes, <italic>ackA</italic> and <italic>cysK</italic>. Expression of these genes was significantly correlated to the production of the anti-inflammatory and antitumor metabolites daphnoretin and bufalin.</p></sec>