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Friday, January 9, 2015

The gut microbiota and inflammatory non-communicable diseases: Associations and potentials for gut microbiota therapies

The health of our modern society is being threatened by a plethora of chronic inflammatory non-communicable diseases (NCDs) which share in common, an underlying low-grade inflammation. These include early onset NCDs such as allergy, asthma and some autoimmune diseases and later onset NCDs including cardiovascular disease (CVD), metabolic disease and neurodegenerative disorders. While inflammation and the pathways to disease are multifactorial, the altered gut colonization patterns associated with declining microbial diversity is a central theme, and increasingly implicated in the physiological, immunological and metabolic dysregulation seen in many NCDs. Upon review of the current literature, West et al discuss the relationships between gut colonization and inflammatory NCDs, and gut microbiota modulation strategies for their treatment and prevention (J Allergy Clin Immunol 2015; 135: 3-13).

The critical role of the gut microbiota in immune development has been well documented in germ free animal models, demonstrating the failure of normal maturation and, in particular, failure of the systemic immune regulatory networks that result in both allergic and autoimmune phenomena. Data from several animal models have formed a basis to further explore the role of gut microbiota in early programming of host responses in humans. Collectively, recent literature suggests that the imprinting of human gut microbiota may commence already in utero and is then further shaped by postnatal exposures such as cesarean or vaginal delivery, antibiotics to the mother or infant, breastfeeding, and introduction to solid foods.

Culture independent DNA-based studies have demonstrated associations between reduced gut microbiota diversity and early onset NCDs including atopy, eczema, and asthma. Furthermore, inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes have been shown to be associated with dysbiosis. It is also suggested that the early microbial environment drives more sustained predisposition to low-grade inflammation into adulthood and the propensity for later onset NCDs. Aberrations in the gut microbiota may also have implications for obesity-associated NCDs.

The most widely used approach for treatment and prevention of NCDs has been to administer probiotics. For example, specific probiotics promote favorable intestinal colonization and their fermented products have anti-inflammatory, immunomodulatory, and metabolic effects, although the effects are variable when evaluated in clinical trials. Fecal microbiota transplantation (FMT) is an emerging therapy that has been successful in the treatment of Clostridium difficile infection and possibly IBD. While much remains unknown, multidisciplinary and integrative approaches may ultimately lead to improved strategies to overcome the disease epidemic of modern civilizations. 

Question for the authors:
Most treatment and prevention research focuses on early development and manipulation of the gut microbiota. What is known about treatment of allergic and autoimmune diseases in adults through diet and lifestyle modifications that directly alter the gut microbiota composition?

Most treatment and prevention research focuses on early development and manipulation of the gut microbiota. What is known about treatment of allergic and autoimmune diseases in adults through diet and lifestyle modifications that directly alter the gut microbiota composition?

There is clear evidence that diet impacts gut microbiota composition, however intervention studies aiming at modulating the gut microbiota in adults with allergic or autoimmune disease are scarce.  Dietary patterns such as the Mediterranean diet have been associated with increased asthma control in cross-sectional studies although the effect on gut microbiota composition was not studied. However, there is some support that a Mediterranean-style diet may influence gut microbiota.  In a small pilot study, Marlow et al 2013, examined the effects of a Mediterranean-influenced dietary intervention on inflammatory biomarkers and gut microbiota in eight Crohn’s disease patients. This 6-week dietary intervention resulted in a trend for reduced inflammation and ”normalised” gut microbiota with an increase in Bacteroidetes and the Clostridium clusters, and a decrease in Proteobacteria and Bacillaceae.

Even though most probiotic prevention and treatment studies have targeted a pediatric population, there are also randomized controlled trials with probiotics (although most commonly given as supplements and not incorporated in the diet) for treatment of allergic disease also in adults. The results have been variable, although meta-analyses generally show no benefit of probiotics for treatment of allergic disease.

The impact of lifestyle modifications other than diet in this context is even less studied. Benjamin et al 2012, reported smoking to be associated with an increase in Bacteroides-Prevotella both in patients with active Crohn’s disease and in healthy controls suggesting that smoking may at least partially contribute to the dysbiotic state. Stress is another lifestyle  factor with potential to impact gut microbiota composition via the gut-brain axis, however there is a paucity of studies in the context of allergic and autoimmune disease.

Clearly, there is need for well-designed dietary and life-style intervention studies targeting gut microbiota in both allergic and autoimmune disease.

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