Comprehensive Probiogenomics Analysis of the Commensal Escherichia Coli CEC15 as a Potential Probiotic Strain
Author:
Silva Tales Fernando da1, Glória Rafael de Assis2, Sousa Thiago de Jesus2, Americo Monique Ferrary2, Freitas Andria dos Santos1, Viana Marcus Vinicius Canário2, de Jesus Luis Claudio Lima2, Prado Ligia Carolina da Silva1, Daniel Nathalie1, Ménard Olivia1, Cochet Marie-Françoise1, Dupont Didier1, Jardin Julien1, Borges Amanda Dias3, Fernandes Simone Odília Antunes3, Cardoso Valbert Nascimento3, Brenig Bertram4, Ferreira Enio5, Profeta Rodrigo2, Aburjaile Flavia Figueira6, Carvalho Rodrigo Dias de Oliveira7, Langella Philippe8, Loir Yves Le1, Cherbuy Claire8, Jan Gwénaël1, Azevedo Vasco2, Guédon Éric1
Affiliation:
1. INRAE, Institut Agro, STLO, UMR1253 2. Institute of Biological Sciences, Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais 3. Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais 4. Department of Molecular Biology of Livestock, Institute of Veterinary Medicine, Georg-August Universität Göttingen 5. Department of general pathology, Federal University of Minas Gerais 6. Veterinary school, Federal University of Minas Gerais 7. Federal University of Bahia 8. Université Paris Saclay, INRAE, AgroParisTech, UMR1319, MICALIS
Abstract
Abstract
Background: Probiotics have gained attention for their potential maintaining gut and immune homeostasis. They have been found to confer protection against pathogen colonization, possess immunomodulatory effects, enhance gut barrier functionality, and mitigate inflammation. However, a thorough understanding of the unique mechanisms of effects triggered by individual strains is necessary to optimize their therapeutic efficacy. Probiogenomics, involving high-throughput techniques, can help identify uncharacterized strains and aid in the rational selection of new probiotics. This study evaluates the potential of the Escherichia coli CEC15 strain as a probiotic through in silico, in vitro, and in vivo analyses, comparing it to the reference E. coli Nissle 1917. Genomic analysis was conducted to identify traits with potential beneficial activity and to assess the safety of each strain (genomic islands, bacteriocin production, antibiotic resistance, production of proteins involved in host homeostasis, and proteins with adhesive properties). In vitro studies assessed survival in gastrointestinal simulated conditions and adhesion to cultured human intestinal cells. Safety was evaluated in BALB/c mice, monitoring the impact of E. coliconsumption on clinical signs, intestinal architecture, intestinal permeability, and fecal microbiota. Additionally, the protective effects of both strains were assessed in a murine model of 5-FU-induced mucositis.
Results:CEC15 mitigates inflammation, reinforces intestinal barrier and modulates intestinal microbiota. In silico analysis revealed fewer pathogenicity-related traits in CEC15, when compared to Nissle 1917, with fewer toxin-associated genes and no gene suggesting the production of colibactin (a genotoxic agent). The majority of predicted antibiotic-resistance genes were neither associated with actual resistance, nor with transposable elements. The genome of CEC15 strain encodes proteins related to stress tolerance and to adhesion, in line with its better survival during digestion and higher adhesion to intestinal cells, when compared to Nissle 1917. Moreover, CEC15 exhibited beneficial effects on mice and its intestinal microbiota, both in healthy animals and against 5FU-induced intestinal mucositis.
Conclusions: These findings suggest that the CEC15 strain holds promise as a probiotic, capable of modulating the intestinal microbiota, providing immunomodulatory and anti-inflammatory effects, and reinforcing the intestinal barrier. These findings may have implications for the treatment of gastrointestinal disorders, particularly inflammatory bowel disease.
Publisher
Research Square Platform LLC
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