Free Fatty Acids Profiles Are Related to Gut Microbiota Signatures and Short-Chain Fatty Acids

A growing body of evidence highlights the relevance of free fatty acids (FFA) for human health, and their role in the cross talk between the metabolic status and immune system. Altered serum FFA profiles are related to several metabolic conditions, although the underlying mechanisms remain unclear. Recent studies have highlighted the link between gut microbiota and host metabolism. However, although most of the studies have focused on different clinical conditions, evidence on the role of these mediators in healthy populations is lacking. Therefore, we have addressed the analysis of the relationship among gut microbial populations, short-chain fatty acid (SCFA) production, FFA levels, and immune mediators (IFNγ, IL-6, and MCP-1) in 101 human adults from the general Spanish population. Levels of selected microbial groups, representing the major phylogenetic types present in the human intestinal microbiota, were determined by quantitative PCR. Our results showed that the intestinal abundance of Akkermansia was the main predictor of total FFA serum levels, displaying a negative association with total FFA and the pro-inflammatory cytokine IL-6. Similarly, an altered FFA profile, identified by cluster analysis, was related to imbalanced levels of Akkermansia and Lactobacillus as well as increased fecal SCFA, enhanced IL-6 serum levels, and higher prevalence of subclinical metabolic alterations. Although no differences in nutritional intakes were observed, divergent patterns in the associations between nutrient intakes with intestinal microbial populations and SCFA were denoted. Overall, these findings provide new insights on the gut microbiota–host lipid metabolism axis and its potential relevance for human health, where FFA and SCFA seem to play an important role.This work was funded through the Grant GRUPIN14-043 “Microbiota Humana, Alimentación y Salud” funded by “Plan Regional de Investigación del Principado de Asturias,” Asturias, Spain and by the grants AGL2010-14952 from Spanish “Plan Nacional I+D+I” and by Biopolis SL within the framework of the e-CENIT Project SENIFOOD from the Spanish Ministry of Science and Innovation. JR-C and NS benefit from postdoctoral contracts supported by the Grant GRUPIN14-043 and by a Clarín regional contract cofinanced by the Marie Curie CoFund European Program, respectively. Regional grants received cofounding from European Union FEDER funds.The authors acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe