A Randomised Controlled Trial of a Probiotic Lactobacillus Strain in Healthy Adults: Assessment of its Delivery, Transit and Influence on Microbial Flora and Enteric Immunity

Abstract

In severa l intestinal disease states, altered micro ora, impaired gut barrier and:or intestinal in ammation offer a rationale for the effective therapeut ic use of probiotic microorganisms. However , for most candidat e probiotic organisms there is a lack of evidence detailing their characterisation and effects on host ora and immunity. We have previously reported the isolation and characterisation, from surgically resected segment s of the huma n gastrointestinal tract (GIT), of potential probiotic lactic acid bacteria (LAB). We have also described subsequen t animal experimen ts that evaluated the establishment , persistence and localisation of speci c probiotic Lactobacillus strains within the murine intestinal tract, in addition to their ability to in uence the developmen t of murine in ammatory disorders. In these studies, transit and surviva l of Lactobacillus salivarius U CC118 at the ileum was demonstrat ed using enteral tube sampling of six healthy volunteer s following consumption of a single dose (150 ml) of fermented milk-born e probiotic (10 8 colony forming units per ml (CF U :ml)). Subsequently, we performed a randomised controlled trial of 80 volunteer s fed strain UCC118 (10 8 CF U:day for 21 d), using two oral delivery vehicles (fresh milk, n ¾ 20 vs. fermented milk, n ¾ 20; controls, n ¾ 20 for each). Throughout this feeding period , and for up to 100 days following cessation of feeding, the number s of total culturable lactobacilli and of the administered Lactobacillus U CC118 present in faeces were monitored. F ive subjects (5:40; fresh milk, four; fermented milk, one) were still excretin g the probiotic lactobacilli 21 days post-cessatio n of feeding, while one subject (fermented milk) was still colonised up to 100 days after feeding. Consumpt ion of fermented milk-born e UCC118 cells resulted in signi cantly increased levels of faecal-borne enterococci and lactobacilli. N umber s of bi dobacteria, coliforms and bacteroides were not signi cantly altered. In addition, changes in salivary IgA levels against U CC118 cells and increased granulocyt e phagocytic activity were observed following consumption of the fermented milk-borne probiotic. In summary, Lactobacillus UCC118 was found to effectively transit (and persist within) the human intestinal tract, to modify the faeca l ora and to engage the immune system.

Mechanisms of adherence of a probioticLactobacillusstrain during and afterin vivoassessment in ulcerative colitis patients

“…There has been unresolved speculation as to whether the health benefits associated with probiotic consumption are dependent on the microorganisms becoming long-term residents in the gut. However, in this study the introduced lactobacilli were detected at levels comparable to those observed in the previously reported studies (24,36), and they remained recoverable, at least at low levels, for a period of 7 days after cessation of consumption. This suggests that continual ingestion of beneficial microbes will probably be required for most individuals if probiotics in their current form are to be exploited for enhancement of health.…”

“…As in previous studies completed in healthy volunteers (36) and mild-moderately active Crohn's disease patients (24), the probiotic bacteria were administered to the ulcerative colitis patients as components of a fermented milk product. There has been unresolved speculation as to whether the health benefits associated with probiotic consumption are dependent on the microorganisms becoming long-term residents in the gut.…”

Survival ofLactobacillus caseiin the Human Digestive Tract after Consumption of Fermented Milk

“…The apparent survival of L. casei DN-114 001 Rif was greater during the first 2 h of collection (51.2% to 10.0%) than what had been previously reported for other lactobacilli in the ileum (e.g., 0.5% for Lactobacillus fermentum KLD [24]; 1.5% for a commercial strain of Lactobacillus acidophilus [16]) or in the small intestine (e.g., 7% and 11.8% for Lactobacillus plantarum NCIMB 8826 [24] and for Lactobacillus salivarius UCC118 [5], respectively).…”

Influence of Adhesion and Bacteriocin Production by Lactobacillus salivarius on the Intestinal Epithelial Cell Transcriptional Response

“…This has been demonstrated for a number of bacteria, including Escherichia coli, where colicin producers were more persistent than nonproducers (16), and Streptococcus mutans, where a mutant with enhanced mutacin production was more successful at colonizing the oral tract than the wild-type strain (18). UCC118 is strongly adherent to epithelial cells (47) and is known to be able to persist in the gut for a substantial length of time after ingestion (8). The induction of bacteriocin gene expression reported here is likely to enhance the colonization potential of L. salivarius through inhibition of competing organisms and may well be a factor in the persistence of UCC118 in the gastrointestinal tract (GIT).…”