Abstract
BackgroundThe 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 Bifidobacterium breve UCC2003 and the generally regarded as safe (GRAS) organism Lactococcus lactis NZ9000.ResultsIn vitro bile tolerance of both strains was significantly enhanced (P < 0.001), following heterologous expression of the Listeria monocytogenes bile resistance mechanism BilE. Strains harbouring bilE were also recovered at significantly higher levels (P < 0.001), than control strains from the faeces and intestines of mice (n = 5), following oral inoculation. Furthermore, a B. breve strain expressing bilE demonstrated increased efficacy relative to the wild-type strain in reducing oral L. monocytogenes infection in mice.ConclusionCollectively the data indicates that bile tolerance can be enhanced in Bifidobacterium and Lactococcus species through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract.
Highlights
The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel
Proof that the operon was heterologously expressed in both bacterial strains was evident as a single mRNA transcript was obtained by reverse transcription polymerase chain reaction (RT-PCR) analysis (Fig. 2) in vitro studies showing increased bile resistance supports this by indicating that the bile resistance locus was functional
We utilised levels of porcine bile (1% w/v) that were lethal for the bacterial species examined and are likely to approximate in vivo levels in regions of the small intestine where bile is most concentrated [20]
Summary
The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. Proof of principle and efficacy has been demonstrated with the inert food organism Lactococcus lactis which has been engineered to secrete IL-10 locally within the gut in murine models of IBD in order to alleviate symptoms of gastrointestinal inflammation [7]. Despite their obvious clinical potential, these strains are often poorly adapted to conditions encountered in the upper gastrointestinal tract (page number not for citation purposes). Sleator et al, (2005) have shown that bilE does not play a role in osmotolerance, but a major role in bile tolerance
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