Figure 1: Interplay of gut microbiome-intestinal epithelial cells (enterocytes, goblet cells and paneth cells) and host metabolism and immunity. The commensal, symbiotic, and pathogenic microorganisms provide a great variety of nutrients and metabolites for host metabolism, for energy homeostasis of organs and tissues, and for the innate and adaptive immune cell activation and function. A shift toward dysbiosis results from a decrease in symbiont and/or an increase in pathobiont bacteria in intestinal lumen. Increases in nitrate and oxygen (O2) allow the growth of facultative anaerobic bacteria. Increase in the gut permeability and release of PAMPs, such as peptidoglycan and LPS, and DAMPs, such as double-stranded RNA, mtDNA, and ATP. Increase in the production of cytokines, chemokines, nitric oxide (NO), and reactive oxygen species (ROS) by dendritic cells and macrophages causes local and systemic inflammation. Chronic, low-grade systemic inflammation leads to impaired insulin action, insulin resistance, obesity, hypertension, and metabolic syndrome. Probiotics, prebiotics, fecal therapy, and small molecules targeting host genes and specific bacterial species or phylum/class may help to reestablish tissue homeostasis and microbiome healthy. SCFAs: short-chain fatty acids; PAMPs: pathogen-associated molecular patterns; DAMPs: damage-associated molecular patterns; LPS: lipopolysaccharide; AMPs: antimicrobial peptides; IgA: immunoglobulin A.