# Mitigating gut dysbiosis induced by biofilm-forming pathogens: therapeutic potential of LAB-derived bacteriocins

## TL;DR

This study explores how bacteriocins from Lactiplantibacillus pentosus C82 can combat gut dysbiosis and inflammation, offering a potential natural therapy for gut and neurological health.

## Contribution

The study identifies a novel LAB-derived bacteriocin with antibiofilm, anti-inflammatory, and gut-protective properties, validated in a zebrafish model.

## Key findings

- Lactiplantibacillus pentosus C82 bacteriocin showed strong antimicrobial activity against E. coli and S. marcescens.
- The bacteriocin improved gut barrier integrity and reduced inflammation in a zebrafish model.
- It modulated key immune and gut health markers like IL-10, Claudin-5a, and TNF-α.

## Abstract

The gut-brain axis plays a critical role in bidirectional communication system connecting intestinal and neurological health. Imbalance in this system, often caused by gut dysbiosis and pathogenic biofilm formation, can result in inflammation, intestinal barrier dysfunction, and microbial imbalance.

LAB isolates were screened for antimicrobial and antibiofilm activity against Escherichia coli and Serratia marcescens. The most effective strain, C82, was identified through morphological, biochemical and 16S rDNA sequencing. Bacteriocin production, and stability were assessed and optimized. The functional efficacy of the bacteriocin was tested in a zebrafish larval gut dysbiosis model.

Lactiplantibacillus pentosus C82, confirmed through 16S rDNA sequencing (NCBI GenBank submission ID: SUB14502111, accession number PP860573), demonstrated strong antimicrobial activity, with inhibition zones of 1.2 cm against E. coli and 1.4 cm against S. marcescens. The bacteriocin reduced inflammation and improved gut barrier integrity. It upregulated IL-10, Claudin-5a, ZO-1, Nfe2l2a, and Hmox1a, while downregulating TNF-α, csgD, and bsmA.

These results establish L. pentosus C82 bacteriocin as a safe, stable, and potent natural antimicrobial agent with significant antibiofilm, antioxidative, and gut-protective effects. It shows promise as a bio-therapeutic candidate for restoring microbial balance, addressing gut dysbiosis, and influencing the gut-brain axis. However, the study was limited to short-term evaluation in zebrafish larvae, which may not fully represent the complexity of the mammalian gut. Further research involving long-term exposure and higher animal models is necessary to validate its therapeutic potential.

Illustration comparing a healthy state and Parkinson's disease in the context of the gut-brain axis. On the left, healthy conditions show regulated immune cell activation, BBB integrity, and a balanced gut microbiome with increased Lactobacillus and Bifidobacterium. Anti-inflammatory responses are indicated with IL-10 and TGF-β. On the right, Parkinson's disease displays BBB leakage, neuroinflammation, immune dysregulation, and increased pro-inflammatory cytokines like TNF-α, IL-6, IL-1β. There is gut dysbiosis with increased E. coli and S. marcescens and a decrease in beneficial bacteria. The diagram emphasizes the role of dietary fiber and the vagus nerve.