# The Mechanism of Ultrasonic Lysis of Enterococcus faecium F11.1G in Repairing LPS-Induced Inflammatory Damage in IECs via RNA-seq and LC-MS

## TL;DR

Ultrasonic disruption of Enterococcus faecium F11.1G reduces inflammation in intestinal cells by suppressing pro-inflammatory signals and regulating key metabolic pathways.

## Contribution

This study reveals a novel postbiotic mechanism where ultrasonicated E. faecium F11.1G modulates inflammation via NF-κB/MAPK pathways and purine/endocannabinoid metabolism.

## Key findings

- Ultrasonicated E. faecium F11.1G significantly reduces LPS-induced secretion of IL-6, IL-8, IL-1β, and TNF-α in intestinal epithelial cells.
- The anti-inflammatory mechanism involves inhibition of NF-κB/MAPK signaling and regulation of purine and endocannabinoid metabolic networks.
- Key genes like IL-1β, TNF, and TNFAIP3 are identified as part of the inflammatory response modulated by F11.1G.

## Abstract

What are the main findings?
Ultrasonicated Enterococcus faecium F11.1G effectively alleviates the LPS-induced inflammatory damage in intestinal epithelial cells.108 CFU/mL F11.1G significantly suppresses the excessive secretion of pro-inflammatory factors (IL-6, IL-8, IL-1β, and TNF-α).The anti-inflammatory mechanism of F11.1G primarily involves inhibiting the activation of the NF-κB/MAPK signaling pathways and may synergistically regulate the purine/endocannabinoid metabolic networks.

Ultrasonicated Enterococcus faecium F11.1G effectively alleviates the LPS-induced inflammatory damage in intestinal epithelial cells.

108 CFU/mL F11.1G significantly suppresses the excessive secretion of pro-inflammatory factors (IL-6, IL-8, IL-1β, and TNF-α).

The anti-inflammatory mechanism of F11.1G primarily involves inhibiting the activation of the NF-κB/MAPK signaling pathways and may synergistically regulate the purine/endocannabinoid metabolic networks.

What are the implications of the main findings?
These findings provide experimental evidence supporting the potential of ultrasonicated Enterococcus faecium F11.1G as a postbiotic agent for alleviating intestinal inflammation.The study suggests that F11.1G exerts its anti-inflammatory effects through multi-target modulation of inflammatory signaling pathways and metabolic networks.

These findings provide experimental evidence supporting the potential of ultrasonicated Enterococcus faecium F11.1G as a postbiotic agent for alleviating intestinal inflammation.

The study suggests that F11.1G exerts its anti-inflammatory effects through multi-target modulation of inflammatory signaling pathways and metabolic networks.

Lipopolysaccharide (LPS)-induced damage to the intestinal epithelial barrier leads to gut inflammation, and intracellular metabolites of lactic acid bacteria may participate in regulating this process to exert probiotic effects. This study aimed to investigate the repair effects and molecular mechanisms of ultrasonic disruption-treated Enterococcus faecium F11.1G (F11.1G) on the model (primary lamb IECs + 5 μg/mL LPS for 6 h). Then, results demonstrated that 108 CFU/mL F11.1G significantly suppressed the excessive secretion of pro-inflammatory factors (IL-6, IL-8, IL-1β, TNF-α) induced by LPS. Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) were primarily enriched in cellular response to lipopolysaccharide, inflammatory response, and canonical NF-κB signaling pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment in NF-κB signaling pathway and MAPK signaling pathway. PPI network identified key genes including IL-1β, TNF, IL-8, RELB, FOS, TNFAIP3, NFKBIA, and MMP9. KEGG analysis indicated differentially abundant metabolites (DAMs) enrichment in purine metabolism and the endocannabinoid system. Spearman correlation analysis revealed positive correlations between pro-inflammatory genes and endogenous protective metabolites, such as adenosine and PEA, while showing negative correlations with multiple purine metabolites. Correlational analysis indicates that F11.1G alleviates intestinal inflammatory damage primarily by suppressing NF-κB/MAPK pathway activation and may synergistically regulate purine and endocannabinoid metabolism.