Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials

Abstract

The enteric flora comprise approximately 95% of the total number of cells in the human body and are capable of eliciting immune responses while also protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract (GIT) may also be implicated in the pathogenesis of several chronic conditions such as inflammatory bowel disease (IBD). The University College Cork-based Probiotic Research Group has successfully isolated and identified lactic acid bacteria (LAB) which exhibit beneficial probiotic traits. These characteristics include the demonstration of bile tolerance; acid resistance; adherence to host epithelial tissue; and in vitro antagonism of potentially-pathogenic micro-organisms or those which have been implicated in promoting inflammation. The primary objective of this report is to describe the strategy adopted for the selection of potentially effective probiotic bacteria. The study further describes the evaluation of two members of the resulting panel of micro-organisms (Lactobacillus salivarius subsp. salivarius UCCl18 and Bifidobacterium longum infantis 35624) under in vitro conditions and throughout in vivo murine and human feeding trials. Specifically, an initial feeding study completed in Balb/c mice focused upon (i) effective delivery of the probiotic micro-organisms to the GIT and evaluation of the ability of the introduced strains to survive transit through, and possibly colonise, the murine GIT; (ii) accepting the complexity of the hostile GIT and faecal environments, development of a method of enumerating the introduced bacterial strains using conventional microbiological techniques; and (iii) assessment of the effects of administered bacterial strains on the numbers of specific recoverable indigenous bacteria in the murine GIT and faeces. Additional research, exploiting the availability of murine models of inflammatory bowel disease, demonstrated the beneficial effects of administering probiotic combinations of Lactobacillus salivarius UCC1l8 and Bifidobacterium longum in/antis 35624 in prevention of illness-related weight loss. A further ethically-approved feeding trial, successfully conducted in 80 healthy volunteers, demonstrated that yoghurt can be used as a vehicle for delivery of Lactobacillus salivarius strain UCCl18 to the human GIT with considerable efficacy in influencing gut flora and colonisation.

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

“…This study describes the behaviour and effects, following its administration to healthy adult humans, of L. salivarius U CC118, a strain which was originally isolated from the ileal-caecal region of the intestinal tract of a healthy human adult (20,21). Previously, speci c criteria were employed to determine the suitability of the strain for use as a probiotic.…”

“…Previously, speci c criteria were employed to determine the suitability of the strain for use as a probiotic. These included the ability of the strain to survive in human gastric acid at pH 2.5 and growth at physiological concentrations of human bile (0.03% v:v) (20,21). Strain U CC118, originally isolated as crypt-adhering bacteria, was also previously con rmed to be strongly adhesive to the human adenocarcinoma cell lines Caco-2 and H T-29 (20,21).…”

“…These approaches resulted in the isolation of Lactobacillus strains from healthy human adults (20,21) and their subsequent assessment in murine models (22). In this study, our objective was to further characterise the probiotic Lactobacillus salivarius strain U CC118 and to focus speci cally upon: (i) effective delivery of the probiotic micro-organism to the human gut using fermented and non-fermented delivery vehicles; (ii) evaluation of the ability of the strain to survive transit through (and persist within) the human intestinal tract; (iii) accepting the complexity of the hostile intestinal and faecal environments, assessment of a method of enumerating the introduced bacterial strain using conventional microbiological techniques; (iv) determining the effect of probiotic consumption on the numbers of faecal-borne selected indigenous bacteria; and (v) evaluation of immune recognition of the consumed probiotic bacteria.…”

A Mucus Adhesion Promoting Protein, MapA, Mediates the Adhesion ofLactobacillus reuterito Caco-2 Human Intestinal Epithelial Cells

“…1,2) In recent years, the relationship between resident LAB and the host animal and the role of colonization of the GI tract by LAB in promoting the health of the host (that is, their benefit as probiotics) have garnered attention. 3,4) In particular, adhesion of LAB to the host GI tract is considered an important factor in this health-promoting effect, because it triggers physiological, immunological stimulation in host animals. Therefore, the adhesion of LAB to the GI tract or colonization to the GI tract by these organisms has been investigated using mucus, tissue samples, cell lines, and components of the extracellular matrix.…”

Fermented milks: a historical food with modern applications–a review

“…However, the microflora of the human intestinal tract in both infants and adults is highly complex and many bacterial species have been identified; the topic has been extensively researched, and the following selected reviews provide relevant information with specific emphasis on probiotic microorganisms and their health applications to humans (Robinson, 1991;Fuller, 1992Fuller, , 1997Sanders, 1994;Salminen et al, 1996aSalminen et al, , 1998bMarshall & Tamime, 1997a;Holzapfel et al, 1998;Salminen & von Wright, 1998;Dunne et al, 1999;Hirayama & Rafter, 1999;Lee et al, 1999;Tannock, 1999;Fuller & Perdigon, 2000;Salminen, 2001). Periodically, Danone Vitapole Recherché publishes monographs (Capron et al, 2000;Malagelada et al, 1999;Denariaz et al, 1999;Gibson et al, 2000;Hartley et al, 2001) and World Newsletter (23 issues have been published) updating the health aspects associated with fermented milks.…”