The mammalian gastrointestinal tract is much more complex than previously appreciated. A single layer of epithelial cells covers the entire gastrointestinal tract, so providing the largest interface with the environment. The gut epithelium is a sensor of the luminal environment, not only controlling digestive, absorptive, and secretory functions, but also relaying information to the mucosal immune, vascular and nervous systems. These functions involve a complex array of pattern recognition receptors (PRRs) and cell types that elaborate growth factors, cytokines, and extracellular matrix proteins. Moreover, enteric microbes may hijack PRR-activated pathways as part of their pathogenic arsenal through ‘host mimicry’. Understanding the cross-talk between enteric microbiota and the host under both physiological and pathological circumstances may provide key information on the pathogenesis of local as well as systemic diseases. This knowledge may potentially lead to the identification of novel therapeutic strategies for the treatment of these disorders.
The hygiene hypothesis links the growing epidemic of clinical manifestations of allergy, atopic eczema, allergic rhinoconjunctivitis and asthma to reduced exposure to microbes at an early age as a result of environmental changes in the industrialized world. These include improved sanitation and living conditions, vaccinations and antimicrobial therapy, together with declining family size and changes in dietary intake. The discovery of three subgroups of regulatory T cells has revolutionized the original immunological basis of the hygiene hypothesis, the so-called T helper 1/T helper 2 paradigm. In a case of defective oral tolerance allergy ensues. Recent experimental and clinical findings clearly indicate that both the development and maintenance of oral tolerance is dependent on these immunosuppressive regulatory T cells. Moreover, gut microbiota has been demonstrated to be crucial for the appropriate expression and function of the regulatory T cells, thus connecting microbiota closely to allergy. Indeed, many of the cross-sectional studies have shown a different composition of gut microbiota in children with atopic eczema and healthy controls. Most of the published prospective follow-up studies so far have also found that alterations in gut microbiota precede development of allergy. Changes in the amount of bifidobacteria, clostridia and Escherichia coli have been the most common findings in these studies. There has been, however, considerable variation in the settings of different prospective studies, making it difficult to interpret probable causes for variable results. The future studies addressing the issue should not only use novel molecular techniques of gut microbiota assessment, but also take into consideration several other aspects discussed in this paper.
Crohn’s disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract that together comprise a spectrum of diseases entitled inflammatory bowel disease (IBD). The human intestine is colonized with commensal microbiota in concentrations that exceed the number of cells in the human body. Under normal physiologic conditions there is an interplay between these bacteria and the human host in a process that maintains the integrity of the immune system in health and disease. Gut microbiota play an important role in IBD. Commensal and pathologic bacteria comprise part of the etiology of IBD, and the gut microbiota in patients with IBD is different from that in healthy controls. Their influence is probably brought about in initiation of disease as well as in flare-ups, and it is logical to assume that manipulation of the gut microbiota could be a preventive measure in IBD evolution and may play a therapeutic role in disease exacerbation. This review will briefly discuss issues related to studying gut microbiota, the interplay of these microbiota with the immunologic system in IBD, and focus on the role of microbiota in the etiology, flare-ups and treatment of IBD.
The growing epidemic of obesity is no longer restricted to developed countries. In 2005, the World Health Organization alerted that there were approximately 400 million obese adults worldwide, and approximately 20 million children worldwide were overweight. Obesity is a complex health issue with serious consequences such as type 2 diabetes, cardiovascular diseases, and others. Behavioral, genetic and environmental factors have been addressed as contributing factors for overweight and obesity. Recent evidence indicates that the community of microorganisms that dwell in the gut, known as the gut microbiota, can influence nutrient absorption and energy storage. The microbiotic composition has been shown to differ between obese and lean mice and humans alike, suggesting that modulation of the gut microbiotic composition offers a new avenue for the treatment of obesity and overweight. This review revises the available scientific evidence supporting these speculations. Recent results obtained from studies focusing on the contributions of gut microbiota to diabetes are also summarized in this review.