LAUSR

ost immune responses and the gut microbiota are Htightly connected and collectively contribute to the regulation of metabolic homeostasis. Disturbance of this interplay is implicated in the development of the metabolic syndrome, a multifactorial condition characterized by insulin resistance, dysglycemia, hypercholesterolemia, hypertension, and hepatic steatosis. The underlying pathogenic mechanisms are complex and not completely understood; however, obesity or visceral adiposity stands as a primary trigger, driven by complex cellular mechanisms of de novo lipogenesis and insulin resistance. A main risk factor for obesity-associated metabolic syndrome is chronic consumption of low-fiber, high-fat Western-style diet (WSD). WSD is known to modulate host immunity to promote inflammatory processes in a variety of organs including gut, liver, and fat tissue. Macrophage polarization toward M1 phenotypes seems to play an important role in developing systemic inflammation. In addition, gut microbiota composition changes rapidly in response to dietary modification, and shifts in bacterial composition and function, often referred to as dysbiosis, have been described in patients with metabolic disease, suggesting that the influx of detrimental bacterial products or changes in bacterial metabolism promote chronic “low-grade” tissue inflammation. A decade ago, the scientific community started to unravel the complex role of gut microbial triggers in promoting obesityassociated metabolic disorders. In this issue, Tran et al focus on studying the contribution of the gut microbiota and the downstream inflammatory signaling pathways in WSD-induced adipose tissue inflammation and metabolic disturbances. To confirm the relevance of gut bacteria to host phenotype, the authors used 3 approaches to modulate the microbiota composition, namely germ-free mice, conventional mice treated with antibiotics, and ex–germ-free mice colonized with the previously characterized 8-member minimal consortium, altered Schaedler Flora (ASF), known to mimic normal gut microbiota physiology. Interestingly, absence of microbiota resulted in the amelioration of metabolic disturbances such as dysglycemia and elevated serum cholesterol levels, as well as inflammation. In contrast to the first observations from Gordon and colleagues in germ-free mice demonstrating that the development of obesity requires the presence of gut bacteria, Gewirtz and colleagues now confirmed recent studies that the absence of complex microbial communities did not reduce WSD-induced weight gain or adiposity. However, microbiota eradication reduced innate immune cell infiltrates and proinflammatory cytokine expression in antibiotic-treated and germ-free mice. Furthermore, ASF and germ-free