Probiotics, Prebiotics, and Commensal Bacteria: Perspectives and Clinical Applications in Gastroenterology

This issue of the Gastroenterology Clinics of North America targets the basic science and clinical applications relating to the role of commensal bacteria in health and disease. Unresolved controversies regarding the mechanisms of action and clinical use of pre- and probiotics are being resolved by basic scientists and clinical investigators. The perspectives and potential clinical applications are offered by an international group of outstanding investigators. Each investigator's work is an expression of his analytic skills and creativity, and this issue represents a rich diversity of investigative research. Our hope is that this issue will provide a platform for understanding the many potential clinical applications in this exciting area of research.

Dysregulated immune responses in genetically susceptible hosts can result in a group of inflammatory and allergic illnesses. The research gives particular emphasis to the manipulation of bacterial flora for the betterment of human host health by the addition of probiotics and prebiotics. The induction of protective immune responses in normal hosts by commensal bacteria is fully discussed.

Dr. Tannock states that the principles of microbial ecology are essential to an understanding of the relationship between the gut microbiota and the human host. A major advance in determining culturable bacterial species involves the revelation that the ribosomal subunit RNA (16S RNA) contained regions of nucleotide base sequences that were highly conserved across the world. These were interspersed with variable V regions containing the signatures of phylogenetic groups and species. This allowed extraction of bacterial RNA and DNA-PCR amplification, making it possible to enumerate the various phylogenetic groups of bacteria inhabiting the human gut. Dr. Tannock confirms that the bacterial community of the large bowel is well regulated and resists minor perturbations. The core or true gut microbiota may be confined to relatively few populations that provide major metabolic activities. Dr. Tannock offers a research road map for future endeavors involving gut microbiota.

Drs. Kalliomaki and Walker provide a molecular and biochemical basis for the protective physiologic processes of commensal bacteria. They clearly demonstrate the interactive relationships of innate and adaptive cellular immunity with an emphasis on microbial epithelial crosstalk. The implications of these findings with reference to Crohn's disease and ulcerative colitis are examined. Possible pathways of inflammatory effects of selected probiotics offer insight as to their mechanism of action.

Drs. MacDonald and Gordon evaluate the extent to which the products of commensal flora regulate immune responses in the gut. A key to understanding the immune response was the discovery of mammalian pattern recognition receptors, the toll-like receptors whose function is to recognize conserved structures on bacteria and viruses. Signaling through toll-like receptors affects dendritic cell function, which in turn will determine T cell differentiation and antibody responses to T-dependent antigens. These authors detail the interactions of microbial flora with dendritic cells and discuss the role of bacterial flora in regulating oral tolerance.

Dr. Bengmark offers a historical perspective of the impact of dietary evolutionary changes on the incidence and prevalence of chronic diseases throughout the world. The microbial connection emphasizes how alteration of bacterial flora may play a significant role in altering human health and in particular inflammatory diseases. He examines the role of antioxidants and complex carbohydrates on chronic illnesses. Finally, he offers an analysis of commercially available pre- and probiotics and their potential clinical application for gastrointestinal diseases.

Drs. Salminen and Isolauri introduce the topic of gut inflammation and barrier function by describing the impact of indigenous microflora on immunophysiologic regulation at an early age. The importance of host–microbe interaction is most vital in the neonatal period, when the establishment of a normal microbiota provides the host with the most substantial antigen challenge, with a strong stimulatory effect on gut-associated lymphoid tissue. Impaired gut barrier may be the explanation for an infant's proneness to allergic and infectious diseases. The authors discuss the promotion of gut barrier by probiotics and the potential for clinical application.

Dr. Vanderhoof and clinical nurse specialist R.J. Young present data relating to bacterial colonization at birth and the subsequent immunologic implications for the infant. Mechanisms of probiotic actions are elucidated, followed by validation of clinical studies relating to diarrheal and allergic illnesses in the pediatric population.

Drs. Rioux, Madsen, and Fedorak discuss the role of bacteria as inciting agents evoking inflammatory bowel disease in genetically predisposed animals and humans. They summarize the literature examining therapeutic efficacy of pre- and probiotics in human inflammatory bowel disease and experimental colitis in animal studies. Evidence classifying methodologic quality of clinical trials in Crohn's disease, ulcerative colitis, and pouchitis is offered. The authors make recommendations for future basic science and clinical research.

Drs. Doron, Snydman, and Gorbach detail historical events leading to the discovery of the most studied lactobacillus: Lactobacillus GG. Bacteriologic characterization and clinical applications are offered.

Strong evidence exists supporting the use of Lactobacillus GG for the treatment and prevention of acute diarrhea in children and antibiotic-associated diarrhea. Potential applications for the treatment and prevention of allergies, childhood respiratory infections, prevention of dental caries, irritable bowel syndrome, and a wide variety of other illnesses are discussed.

Drs. Gionchetti, Lammers, Rizzelo, and Campieri provide an analysis of the basic and clinical contributions of the probiotic VSL#3. The initial studies of this agent on pouchitis provided an impetus for clinical and laboratory investigations of probiotics worldwide. Bacteriological background of patients with inflammatory bowel disease, possible mechanisms of action of probiotics, and the rationale for employing multiple strains of probiotics as therapy are discussed. Clinical studies of VSL#3 in ulcerative colitis, pouchitis, and Crohn's disease are analyzed. Current and future research agendas are discussed.

An in-depth evaluation of the only yeast-derived probiotic, Saccharomyces boulardii, is provided by Drs. Buts and Bernasconi. This agent has been studied in France for over 50 years. The pharmacodynamic properties, mechanisms of action, basic laboratory studies, and clinical applications are detailed. This agent does not materially affect existing microflora, yet it has properties that inactivate bacterial toxins, inhibit toxin binding, stimulate the host immune system, and provide trophic effects on the intestinal mucosa. Treatment of antibiotic-associated diarrhea and Clostridium difficile colitis have demonstrated efficicacy in randomized controlled trials. Further application in traveler's diarrhea, AIDS-related diarrhea, and inflammatory bowel disease are being pursued.

Dr. Quigley explains the theoretic basis for the possible use of probiotics in functional bowel disease. Particular attention is accorded the potential modification of mucosal immune processes following postinfective irritable bowel syndrome. Further evidence of low-grade inflammation and immune activation in irritable bowel syndrome suggests a role for a bacterial dysbiosis possibly correctable with probiotics. This is clearly an area of potential study for functional bowel disease.

Dr. Floch and Mr. Montrose provide an analysis of the literature pertaining to the use of probiotics in humans. They have cataloged the clinical entities and the multiple trials on adults and children. Evidence suggests efficacy in shortening childhood and adult diarrhea, preventing and treating antibiotic-associated diarrhea, and treatment of pouchitis. Further clinical applications await randomized controlled trials.