Various disease states are associated with an imbalance of protective and pathogenic bacteria in the gut, termed dysbiosis. Current evidence reveals that dietary factors affect the microbial ecosystem in the gut. Changes to community structure of the intestinal microbiota are not without consequence considering the wide effects that the microbes have on both local and systemic immunity. The goal of this review is to give insight into the importance of gut microbiota in disease development and the possible therapeutic interventions in clinical settings. We introduce the complex tripartite relationship between diet, microbes and the gut epithelium.
This is followed by a summary of clinical evidence of dietinduced dysbiosis as a contributing factor in the development of gastrointestinal diseases like inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Finally, the current dietary and microbial interventions to promote a healthy microbial
profile will be reviewed.
The paradigm of disease burden in the developed world has changed drastically in the last few decades from predominately infections to immune-mediated diseases (autoimmunity and allergy) because of alterations in the Western lifestyle (improved sanitation, immunizations, antibiotic usage and altered dietary intake). A diverse balanced microbiota is necessary for the development of an appropriate innate and adaptive immune response. There is strong evidence that disruption of the normal colonization process can lead to alterations in the important symbiotic relationship that is necessary for immune homeostasis. For example, infants born by cesarean section or receiving excessive perinatal antibiotics have inadequate initial colonization and aberrant mucosal immune function. As a result, later in childhood, they express an increased incidence in asthma and autoimmune diseases (e.g. celiac disease). An important component of initial colonization is the infant’s diet. Breast milk contains a variety of nondigestible oligosaccharides which function as prebiotics preferentially stimulating proliferation of Bifidobacteria and Lactobacilli , important health-promoting bacteria, and cause fermentation of the oligosaccharides into short-chain fatty acids. In the absence of breastfeeding for the first 6 months of life, formula containing pre- and probiotics
may overcome an initial inadequate colonization process and help establish a normal mucosal immune system.
Overweight and obesity can currently be considered a major threat to human health and well-being. Recent scientific advances point to an aberrant compositional development of the gut microbiota and low-grade inflammation as contributing factors, in conjunction with excessive energy intake. A high-fat/energy diet alters the gut microbiota composition, which reciprocally engenders excessive energy harvesting and storage. Further, microbial imbalance increases gut permeability, leading to metabolic endotoxemia, inflammation and insulin resistance. Local intestinal immunologic homeostasis is achieved by tolerogenic immune responses to microbial antigens. In the context of amelioration of insulin sensitivity and decreased adiposity, the potential of gut microbiota modulation with specific probiotics and prebiotics lies in the normalization of aberrant microbiota, improved gut barrier function and creation of an anti-inflammatory
milieu. This would suggest a role for probiotic/prebiotic interventions in the search for preventive and therapeutic applications in weight management.
Steady advances in our knowledge of the composition and function of the human microbiome at multiple body sites including the gut, skin and airways will likely contribute to our understanding of mechanisms of probiotic action by beneficial microbes. Microbe:microbe and microbe:human interactions are important considerations as we select probiotics for pediatric patients in the future. Although our knowledge about the composition of the microbiome is progressing rapidly, many gaps exist about the functional capacity and metabolic machinery of the human microbiome. Based on a limited amount of data, probiotics appear capable of altering the composition and function of the microbiome. Probiotics may be part of dietary strategies that combine ways to enhance microbiome function with nutrients that may be converted to active compounds promoting human health. Probiotics have yielded beneficial effects in numerous
studies in the context of different diseases in pediatric gastroenterology. These disease states include necrotizing enterocolitis, antibiotic-associated diarrhea and colitis, acute gastroenteritis and irritable bowel syndrome. In the skin and airways, it is unclear if probiotics can affect the function of the microbiome to reduce the impact of diseases such as asthma and atopic dermatitis. An enhanced understanding of the effects of probiotics on the microbiome should facilitate selection of optimal probiotic strains for specific
diseases in the future.