Gerald Friedman, MD, PhD, MS, FACP, MACG, AGAF, Guest Editor

Dr Molinaro and associates note that obesity-related disorders are associated with energy homeostasis and inflammation. Gut microbiota are involved in several host metabolic functions and may play an important role by increasing energy harvest from the diet, by regulating host metabolism, and by modulating inflammation. Experimental data suggest that manipulation of gut microbiota with prebiotics and probiotics can beneficially transiently affect adiposity and glucose metabolism. The authors analyze the potential gut microbiota–driven pathways that could represent novel targets for the treatment of obesity.

Drs Saavedra and Dattilo provide significant information regarding the role of early acquisition of microbiota in the perinatal period and the development of immune function. The time of development, the microbial profile, and the diversity of this ecosystem appear to be critical in eliciting appropriate host responses, especially adaptive immunity. In fact, the gut microbial patterns associated with healthy vaginally born, breast-fed infants differ from those experiencing early life events such as birth by cesarean section, premature birth, lack of breast feeding, and treatment with antibiotics. These early life events, associated with altered microbial composition, are in turn associated with diseases of infancy, childhood, and later life, specifically immune-related conditions. Bifidobacteria and Lactobacilli are nonpathogenic bacteria that elicit beneficial host responses. The possible role of dysbiosis contributing to necrotizing enterocolitis, allergic diatheses, inflammatory diseases, metabolic syndrome, and obesity is discussed.

In a commentary on the safety of probiotics, Dr Shanahan offers information relating to the long record of safety, particularly related to lactobacilli and bifidobacteria. In fact, the risk appears to be low with currently available probiotic products. Safety should be considered on a strain-by-strain basis. Due caution should be accorded patients with indwelling central venous catheters, patients with synthetic cardiac valves, and those with profound immunosuppression.

Dr Isolauri has had a deep and abiding interest in the relationship of developing commensal bacteria and the association of allergic diatheses. She notes that gut microbiota composition can discriminate between allergic and healthy children, and this distinction may antedate clinical manifestations of disease. Bifidobacteria species are the major determinants of disease risk. Diminished presence of this species is associated with an elevated maternal BMI, weight gain during pregnancy, absence of breast feeding, and infant delivery by Caesarean section. Specific probiotics may modulate early microbial colonization, which represents the first intervention target in allergic disease, together with their ability to reverse the increased intestinal permeability characteristic of children with atopic eczema and food allergy. Probiotics also enhance gut-specific IgA responses, which are frequently defective in children with food allergy.

In their discussion of the treatment of necrotizing enterocolitis with probiotics, Drs Kriston Gangu Li and W. Allan Walker provide a concise update of this emerging field. This devastating intestinal disease of preterm infants is the most common gastrointestinal emergency in the neonatal intensive care unit and is associated with significant morbidity and mortality. Several functional characteristics of the immature intestine render the prematurely born infant ill-equipped to manage the multiple microbial challenges of extrauterine life. Probiotic bacteria have the ability to positively influence the process of bacterial colonization and modify immature intestinal immune responses, thereby decreasing the risk of developing necrotizing enterocolitis.Orally administered probiotics represent a promising new area of disease prevention.

Nucleic acid–based methods of analysis are widely used to determine and monitor the composition of microbes. This methodology facilitates logistical planning and execution of microbiota analysis for probiotic, clinical, and nutritional trials using human subjects. It is known that the impact of ingested probiotics is transient, being only detected in the feces while the probiotic is consumed. Drs Lawley and Tannock recommend that temporal studies of the microbiota be carried out, thus providing information regarding the stability/variability of microbiota compositions over time. The methods described in this article range from relatively simple (PCR) to the technically sophisticated (metatranscriptomics). Generally, a study could commence with a screening of samples to determine whether it will be worthwhile expending further time and money on an in-depth analysis. PCR-DGGE (TTGE) or FISH/FC are cost-effective choices for this purpose. An example of this comprehensive approach is provided by a study of the microbiota of ileoanal pouches.

Dr T.J. Borody is a leading investigator in the analysis and clinical application of fecal microbiota transplantation (FMT) in the treatment of gastrointestinal illnesses. This procedure has gained widespread recognition in light of the recent Clostridium difficile infection (CDI) epidemic in Canada, the United States, and Europe. The success rate, particularly in patients with recurrent CDI, has been dramatically impressive. This article provides an overview of the history of FMT, a review of FMT publications for CDI, and a discussion of the concept of the gut microbiota as a virtual organ. The authors then provide a rationale for FMT use in inflammatory bowel disease (IBD) and other possible emerging applications. Finally, a discussion is offered of how FMT is currently performed and how FMT may be performed in the future.

Dr Eamonn Quigley offers clinicians and investigators a concise, even-handed, in-depth analysis of the impact of probiotics on the various subdivisions of functional bowl disorders. An examination of the scientific basis for the use of probiotics in irritable bowel syndrome (IBS) reveals that new onset IBS may follow bacteriologically confirmed bacterial gastroenteritis. Postinfectious IBS may have long-lasting symptoms possibly based on low-grade inflammation and immune activation secondary to microbial–host engagement. Additionally, there is some evidence that inflammatory and immune processes may contribute to enteric neuromuscular dysfunction. Selected probiotics may be of value by exerting antibacterial (or antiviral) effects, increasing secretory IgA production, enhancing barrier function, preventing colonization by pathogenic bacteria, and reducing proinflammatory cytokine activity. There is some evidence that IBS patients may be deficient in strains and numbers of bifidobacteria and lactobacilli. Changes in the composition of microbiota with probiotics may produce beneficial metabolic functions by altering the efficiency of fermentation of complex carbohydrates, improving mucus barrier function, decreasing intraluminal gas production, and affecting motor dysfunction. Modulation of selected microbiota might benefit slow-transit constipated patients by accelerating motor transit. Specific bacteria, particularly selected bifidobacteria strains, have demonstrable impact on improving global symptoms of IBS. Probiotics in general seem to be most effective in reducing symptoms of bloating and flatulence. The role of probiotics in functional bowel disorders remains to be defined, requiring more long-term randomized, placebo-controlled studies defining optimal strain, dose, and formulation.

Dr G. Friedman offers corroborative evidence favoring the use of probiotics in the prevention of symptoms of antibiotic-associated diarrhea (AAD). Lactobacilli, Saccharomyces boulardii , and selected multistrain combinations, in appropriate dosages, are all clinically useful. The safety profile is generally acceptable particularly in view of the short-term use of an antibiotic when accompanied by a probiotic. C difficile colitis is the most common gastrointestinal infection, exceeding all other gastrointestinal infections combined. There has been a dramatic increase in CDI worldwide during the past decade. In-hospital morbidity and mortality, particularly among the elderly, are continuing to rise. In part, this has been related to a virulent strain, NAP1/B1/027, the virulence of which is enhanced by higher levels of toxins A and B, as well as by a greater tendency for recurrent CDI. Antibiotic therapy is a trigger precipitating AAD, which may lead to CDI. Selected probiotics have been effective in reducing AAD and preventing CDI.

Drs Fedorak and Demeria provide an in-depth analysis of probiotic bacteria in the prevention and treatment of IBD. There is little doubt that commensal bacteria play a significant role in the genesis of IBD in genetically predisposed patients. The precise mechanisms involved in the establishment and progression of IBD with respect to the host bacterial populations remain to be elucidated. There is good evidence supporting the use of probiotics in patients who have developed pouchitis. In patients with mild to moderate ulcerative colitis, probiotic preparations have similar efficacy to conventional treatment with aminosalicylates. Currently, there is insufficient evidence to support the use of probiotics in Crohn’s disease. Well-designed, large, randomized controlled trials utilizing specific strains and appropriate dosages are required for probiotics to become mainstream therapy.