The human microbiome is the population of more than 100 trillion microorganisms that live in our gut, mouth, skin and elsewhere in our bodies. These microbial communities have numerous beneficial functions relevant to supporting life. They are needed to digest food, to prevent disease-causing bacteria from invading the body, to develop and maintain the immune system, and to synthesize essential nutrients and vitamins. According to experiment on mice, the types of lipids mice or animal consume affect the composition of their gut microbiota, which influences whether the animals develop obesity-related inflammation. lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased Toll-like receptor (TLR) activation and WAT inflammation and reduced insulin sensitivity compared with mice fed fish oil and that phenotypic differences between the dietary groups can be partly attributed to differences in microbiota composition. Trif?/? and Myd88?/? mice are protected against lard-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. The results indicate that gut microbiota exacerbates metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids. “The type of fat is really important for shaping microbial communities and their functional dynamics,” said Vanessa Leone. (University of Chicago). Consumption of high saturated and trans fat diets is thought to increase the risk of cardiovascular disease through upregulation of blood total- and LDL-cholesterol. On the other hand, health-promoting fats, such as mono and polyunsaturated fats, are crucial in alleviating risk of chronic disease. The typical Western diet is both high in saturated and trans fats while low in mono and polyunsaturated fats, therefore predisposing regular consumers to many health problems. Several human studies have suggested that a high-fat diet increases total anaerobic microflora and counts of Bacteroides. To specifically investigate the effects of different kinds of dietary fat on human gut microbiota, Fava et al. had subjects consume diets of varying fat content. They noted that consumption of a low-fat diet led to increased fecal abundance of Bifidobacterium with concomitant reductions in fasting glucose and total cholesterol, compared to baseline. On the other hand, a high saturated fat diet increased the relative proportion of Faecalibacterium prausnitzii. Finally, subjects with high monounsaturated fat intake did not experience shifts in the relative abundance of any bacterial genera, but did have overall reduced total bacterial load and plasma total- and LDL-cholesterol. In line with these findings, consumption of salmon–which is high in mono and polyunsaturated fats-was not noted to alter fecal microbiota composition. Studies in rats have shown that intake of a high-fat diet results in considerably less Lactobacillus intestinalis and disproportionately more propionate and acetate producing species, including Clostridiales, Bacteroides, and Enterobacteriales. Furthermore, the abundance of Lactobacillus intestinalis is negatively correlated with rat fat mass and body weight 51. Microbial changes have also been shown to control metabolic endotoxemia-induced inflammation in high-fat diet consuming mice. Mouse studies have also compared the differential effects of various lipids on intestinal microflora. A comparison of lard-derived and fish oil-derived lipids revealed that Bacteroidesand Bilophila were increased in lard-fed mice, while Actinobacteria (Bifidobacterium and Adlercreutzia), lactic acid bacteria (Lactobacillus and Streptococcus), and Verrucomicrobia (Akkermansia muciniphila) were increased in fish-oil-fed mice. Furthermore, lard-fed mice had increased systemic TLR activation, white adipose tissue inflammation, and impaired insulin sensitivity compared to mice consuming fish oil. It demonstrated that these findings are at least partly due to differences in gut microbiota between the two groups; transplantation of microbiota from one group to the other after antibiotic administration not only enriched the transplant recipient’s gut with dominant genera from the donor species, but also replicated the donor’s inflammatory and metabolic phenotypes. These results indicate that gut microbiota may promote metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids.