title: Safety assessment of the butyrate-producing Butyricicoccus pullicaecorum strain 25-3(T), a potential probiotic for patients with inflammatory bowel disease, based on oral toxicity tests and whole genome sequencing.
abstract: Inflammatory bowel disease (IBD) is a chronic inflammation of the digestive tract, characterized by dysbiosis of the intestinal microbiota. Probiotics have been suggested as a strategy to reduce active disease or extend remission. We isolated and characterized the butyrate-producing strain Butyricicoccus pullicaecorum 25-3(T) and identified it as a potential probiotic for patients with IBD. To evaluate the safety of 25-3(T) for use in humans, we conducted a standard acute oral toxicity test and a 28-day repeated oral dose toxicity test. The complete genome of B. pullicaecorum 25-3(T) was sequenced to search for virulence factors and antibiotic resistance determinants. The minimum inhibitory concentration (MIC) of 21 antimicrobials was determined. Results showed no adverse effects in the oral toxicity tests. B. pullicaecorum 25-3(T) is resistant against aminoglycosides and trimethoprim. The genome of 25-3(T) contains no virulence factors, one gene related to harmful metabolites and 52 sequences with high similarity to antimicrobial and toxic compound resistance genes, that did not correspond with a resistant phenotype. This first report of a safety assessment of a butyrate-producing strain from Clostridium cluster IV shows that B. pullicaecorum 25-3(T) is a non-pathogenic strain, but carries antibiotic resistance genes with the risk of transfer, that need further investigation.
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Electronic address: Marjan.Steppe@UGent.be.
authors.forename: Marjan
authors.initials: M
authors.lastname: Steppe
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, Ghent, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Nieuwerburgh
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Vercauteren
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Boyen
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Venessa
authors.initials: V
authors.lastname: Eeckhaut
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Ducatelle
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Immerseel
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D002087:Butyrates / Q000378:metabolism; D003257:Consumer Product Safety; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D059022:Food Safety; D016680:Genome, Bacterial; D006094:Gram-Positive Bacteria / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D008826:Microbial Sensitivity Tests; D019936:Probiotics / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA; D018675:Toxicity Tests; D014295:Trimethoprim / Q000494:pharmacology; D037521:Virulence Factors
chemical_list: D000617:Aminoglycosides; D000890:Anti-Infective Agents; D002087:Butyrates; D004269:DNA, Bacterial; D037521:Virulence Factors; D014295:Trimethoprim
keywords: Butyrate; Butyricicoccus pullicaecorum; Genome analysis; MIC; Probiotics; Safety assessment