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In recent decades, obesity has become one of the most common lifestyle-associated disorders. Obesity is a major contributing factor for several other lifestyles associated disorders such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. Although genetics and lifestyle have been directly implicated in the onset and progression of obesity, recent studies have established that gut microbiome plays a crucial role in obesity progression. A higher proportion of Firmicutes and a skewed Firmicutes/Bacteroidetes ratio may contribute to gut dysbiosis and subsequent disturbances in the overall body metabolisms. Like gut microbiome, the oral cavity of humans also harbors a characteristic microbial population called “oral microbiome”. The oral microbiome has also been implicated in the development of obesity due to its modulating effects on the gut microbiome. Due to its critical role in obesity, alteration in the gut microbiome has been suggested as one of the therapeutic strategies to manage obesity itself. For example, fecal microbiome transfer, or the use of probiotics and prebiotics have been suggested. These therapies not only restore the gut microbiome to the “pre-obese stage” but also ameliorate many functional aspects of the metabolic syndrome such as systemic inflammation, insulin resistance, and fat accumulation. However, the efficacy and safety of some of the methods have not been tested for their long-term implications, and further research in this area is warranted to understand the molecular mechanisms involved in this process completely.

Intestinal hyperpermeability is a complex metabolic process mediated by different pathways in close relation to the gut microbiota. Previous studies suggested that the gut microbiota is involved in different metabolic regulations, and its imbalance is associated with several metabolic diseases, including obesity. It is well known that intestinal hyperpermeability is associated with dysbiosis, and the combination of these two conditions can lead to an increase in the level of low-grade inflammation in obese patients due to an increase in pro-inflammatory cytokine levels. Inflammatory bowel syndrome often accompanies this condition causing an alteration of the intestinal mucosa and thus reinforcing the dysbiosis and gut hyperpermeability. The onset of metabolic disorders depends on violations of the integrity of the intestinal barrier as a result of increased intestinal permeability. Chronic inflammation due to endotoxemia is responsible for the development of obesity. Metabolic disorders are associated with dysregulation of the microbiota-gut-brain axis and with an altered composition of gut flora. In this review, we will discuss the mechanisms that illustrate the relationship between hyperpermeability, the composition of the gut microbiota, and obesity.