Probiotics and gastrointestinal disease: successes, problems and future prospects

Abstract

Gastrointestinal disease is a major cause of morbidity and mortality worldwide each year. Treatment of chronic inflammatory gastrointestinal conditions such as ulcerative colitis and Crohn's disease is difficult due to the ambiguity surrounding their precise aetiology. Infectious gastrointestinal diseases, such as various types of diarrheal disease are also becoming increasingly difficult to treat due to the increasing dissemination of antibiotic resistance among microorganisms and the emergence of the so-called 'superbugs'. Taking into consideration these problems, the need for novel therapeutics is essential. Although described for over a century probiotics have only been extensively researched in recent years. Their use in the treatment and prevention of disease, particularly gastrointestinal disease, has yielded many successful results, some of which we outline in this review. Although promising, many probiotics are hindered by inherent physiological and technological weaknesses and often the most clinically promising strains are unusable. Consequently we discuss various strategies whereby probiotics may be engineered to create designer probiotics. Such innovative approaches include; a receptor mimicry strategy to create probiotics that target specific pathogens and toxins, a patho-biotechnology approach using pathogen-derived genes to create more robust probiotic stains with increased host and processing-associated stress tolerance profiles and meta-biotechnology, whereby, functional metagenomics may be used to identify novel genes from diverse and vastly unexplored environments, such as the human gut, for use in biotechnology and medicine.

Figures

Figure 1

Recent advances in the design of more effective probiotic cultures by (A) improving probiotic tolerance to stresses encountered during food manufacture and storage. (B) Improving in vivo resistance to host specific stresses, thus facilitating improved gut colonization and persistence and (C) designer probiotics which specifically target pathogens and/or toxins; thus improving prophylactic and therapeutic effect [52].

Figure 2

Patho-biotechnology - the exploitation of pathogen derived virulence associated and stress survival factors for beneficial applications. Pathogens and probiotics experience an almost identical set of challenges during gastrointestinal transit. A virulence associated factor in a pathogen may thus be exploited as a beneficial host adaptive system in a probiotic [66].

Figure 3

(A) [14C]glycine betaine uptake in the Lactobacillus salivarius wild type (yellow bar) and the BetL complemented strain UCC118-BetL+ (red bar). (B) Growth of L. salivarius wild type (yellow circles) and UCC118-BetL+ (red circles) in MRS broth with 7% added NaCl [77].

Figure 4

(A) Effect of bilE on the gastrointestinal persistence of Bifidobacterium breve bilE+ (black) and Bifidobacterium breve bilE- (white) were used for peroral inoculation of female BALB/c mice (n = 5). Bifidobacterium breve counts were determined in stools at 48 hour intervals. (B) At day 19 mice were sacrificed and Bifidobacterium breve harbouring bilE (white bars) were recovered at significantly higher numbers in the intestines and caeca than the controls (black) [79].