Summary: | <p>Abstract</p> <p>Background</p> <p>The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. However, unlike pathogenic bacteria; they are often inadequately equipped to endure the physicochemical stresses of gastrointestinal (GI) delivery in the host. Herein we outline a patho-biotechnology strategy to improve gastric delivery and host adaptation of a probiotic strain <it>Bifidobacterium breve </it>UCC2003 and the generally regarded as safe (GRAS) organism <it>Lactococcus lactis </it>NZ9000.</p> <p>Results</p> <p><it>In vitro </it>bile tolerance of both strains was significantly enhanced (<it>P </it>< 0.001), following heterologous expression of the <it>Listeria monocytogenes </it>bile resistance mechanism BilE. Strains harbouring <it>bilE </it>were also recovered at significantly higher levels (<it>P </it>< 0.001), than control strains from the faeces and intestines of mice (<it>n </it>= 5), following oral inoculation. Furthermore, a <it>B. breve </it>strain expressing <it>bilE</it> demonstrated increased efficacy relative to the wild-type strain in reducing oral <it>L. monocytogenes </it>infection in mice.</p> <p>Conclusion</p> <p>Collectively the data indicates that bile tolerance can be enhanced in <it>Bifidobacterium </it>and <it>Lactococcus </it>species through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract.</p>
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