Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial

Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.

Food is a primordial need for our survival and well-being. However, diet is not only essential to maintain human growth, reproduction, and health, but it also modulates and supports the symbiotic microbial communities that colonize the digestive tract-the gut microbiota. Type, quality, and origin of our food shape our gut microbes and affect their composition and function, impacting host-microbe interactions. In this review, we will focus on dietary fibers, which interact directly with gut microbes and lead to the production of key metabolites such as short-chain fatty acids, and discuss how dietary fiber impacts gut microbial ecology, host physiology, and health. Hippocrates' notion "Let food be thy medicine and medicine be thy food" remains highly relevant millennia later, but requires consideration of how diet can be used for modulation of gut microbial ecology to promote health.