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Metabolic syndrome is a cluster of three or more metabolic disorders including insulin resistance, obesity, and hyperlipidemia. Obesity has become the epidemic of the twenty-first century with more than 1.6 billion overweight adults. Due to the strong connection between obesity and type 2 diabetes, obesity has received wide attention with subsequent coining of the term “diabesity.” Recent studies have identified unique contributions of the immensely diverse gut microbiota in the pathogenesis of obesity and diabetes. Several mechanisms have been proposed including altered glucose and fatty acid metabolism, hepatic fatty acid storage, and modulation of glucagon-like peptide (GLP)-1. Importantly, the relationship between unhealthy diet and a modified gut microbiota composition observed in diabetic or obese subjects has been recognized. Similarly, the role of diet rich in polyphenols and plant polysaccharides in modulating gut bacteria and its impact on diabetes and obesity have been the subject of investigation by several research groups. Gut microbiota are also responsible for the extensive metabolism of polyphenols thus modulating their biological activities. The aim of this review is to shed light on the composition of gut microbes, their health importance and how they can contribute to diseases as well as their modulation by polyphenols and polysaccharides to control obesity and diabetes. In addition, the role of microbiota in improving the oral bioavailability of polyphenols and hence in shaping their antidiabetic and antiobesity activities will be discussed.The healthy human gut represents a complex and highly variable ecological system consisting of several microbes belonging to bacteria, fungi and virus domains, in addition to host epithelial cells. Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria are the major phyla colonizing the stomach and intestine of healthy adults. The exact role of gut microbiota is not fully elucidated but many studies implicate microbiota to perform tasks that are known to be useful for the human host such as modulating intermediate metabolism and the immune system. Diet-induced changes in the composition/diversity of gut microbes are thus believed to participate in the pathogenesis of certain diseases through modifying different metabolic processes in the host.Less diverse intestinal microbiota have been reported in metabolic disorders. While the association between increased Firmicutes/Bacteroidetes ratio and metabolic diseases is still controversial, more recent studies associated Akkermansia and Lactobacillus species with central obesity and fasting hyperglycemia.Polyphenols, oligo-, and poly-saccharides can influence the composition of gut microbiota by favoring beneficial bacteria and inhibiting growth and activity of pathogenic species and thus constitute a promising avenue for the prevention and treatment of metabolic disorders.Given all the above considerations, the perspectives for targeting the gut microbiome in the context of metabolic diseases keeps being highly relevant and timely. First and foremost, there remains a need to refine research on specific microbes that may be more specifically involved in metabolic diseases rather than considering broader categories, such as phyla. Among challenges that should be met, more studies should focus on the roles and potential mechanisms of action of non-bacterial gut microbes, since these remain poorly understood. Continued research efforts should also result in the better understanding of the modes of action of pre- and pro-biotics in metabolic diseases, notably in terms of metabolic and inflammatory mediators.There also remains a lot to be done to further elucidate the intricate interactions between prebiotics (polyphenols and fibers) on the one hand, and probiotics (gut microbes), on the other, notably in what pertains to the metabolism of prebiotics by the latter and the influence this has on the bioactivity of the former. In this context, experimental approaches and tools have now evolved that can meet this challenge. For instance, one could think of combining bacterial metagenomics with plant metabolomics and hence study relationships through the use of powerful bioinformatics.Overall, and in a very pragmatic sense, academics and industrial partners will need to work together to develop safe and reliable products that can help prevent and mitigate the ill effects of metabolic syndrome and related obesity and diabetes. In this context, a promising approach may be to further explore symbiotic products that can combine pre- and pro-biotics in novel and efficient ways.Eid HM, Wright ML, Anil Kumar NV, Qawasmeh A, Hassan STS, Mocan A, Nabavi SM, Rastrelli L, Atanasov AG and Haddad PS (2017) Significance of Microbiota in Obesity and Metabolic Diseases and the Modulatory Potential by Medicinal Plant and Food Ingredients. Front. Pharmacol. 8:387. doi: 10.3389/fphar.2017.00387