metabolites causing immune reactions. short-chain fatty acids (scfas) have been linked to a decrease in allergic inflammation in asthma while both scfas and b vitamins have been shown to decrease ibd inflammation. scfas (acetate, butyrate and propionate) are metabolites created by bacteria in the gut, these molecules then inhibit histone deacetylases (hdacs) as well as g protein-coupled receptors, acting as signaling molecules. inhibition of hdacs downregulates nuclear factor-κb (nf-κb) and the pro-inflammatory tumor necrosis factor (tnf) as well as having anti-inflammatory effects on macrophages and dendritic cells. activation of mucosal immunity and the intestinal microbiota may contribute to inflammatory bowel disease. many bacteria cause inflammation in the gut including escherichia coli, which replicate in macrophages and secretes cytokine tumor necrosis factor. however, some bacteria, including the human symbiont b. fragilis, may prevent colitis by producing polysaccharide a (psa). psa induces production of il-10, an immunosuppressive cytokine that suppresses inflammation. treatment of bone-marrow-derived dendritic cells and naïve cd4+ t cells with purified psa resulted in increased il-10 production. to mimic colitis and activate inflammatory t cells in an experimental condition, wild-type mice were treated with trinitrobenzen sulphonic acid (tnbs). thereafter, these mice were given psa orally. pro-inflammatory cytokine expression (il-17a and tnfα) in cd4+ cells was measured with elisa. the researchers found that compared to the cd4+ cells in the control mice, cd4+ cells in psa-treated mice produced reduced levels of the pro-inflammatory cytokines il-17a and tnfα. furthermore, after intestinal colonization with b. fragilis, il-23 expression by splenocytes was markedly reduced. these data suggest that psa secreted by b. fragilis suppresses the inflammatory process during colitis by leading to increased production of il-10 and decreased production of il-17, tnfα, and il-23. commensal bacteria may also regulate immune responses that cause allergies. for example, commensal bacteria stimulate tlr4, which may inhibit allergic responses to food. metabolic disorders major metabolic diseases have been found to be impacted by gut microbiota metabolites, including heart disease, kidney disease, type 2 diabetes and obesity. breakdown of l-carnitine from red meat by gut microbes into trimethylamine n-oxide (tmao) has been associated with atherosclerosis, which can lead to obesity, heart disease and type 2 diabetes while both heart and kidney disease events can be predicted by high free p-cresol levels. scfas modulates renin secretion by binding olfr78, lowering blood pressure and decreasing the risk of kidney disease. studies with germ-free mice have suggested that the absence of gut microbes protects against obesity. while the exact mechanism by which microbes play a role in obesity has yet to be elucidated, it has been hypothesized that the intestinal microbiota is involved in converting food to usable energy and fat storage. neurological disorders gut microbiota impacts many facets of human health, even neurological disorders that can caused by molecule or hormone imbalance. autism spectrum disorder (asd), central nervous system dysfunction and depression have all been found to be impacted by the microbiota. blood-brain barrier transport while asd is regularly described by behavioral differences it also can present with gastrointestinal symptoms. dysbiosis of the gi tract has been noted in some asd individuals, leading to an increased intestinal permeability. in the mouse model mice with asd and gi tract dysbiosis (maternal immune activation) increased intestinal permeability was found as was corrected by the introduction of human gut bacterial symbiont b. fragilis. microglia development have a pivotal role in central nervous system dysfunction, bacterial metabolite scfas regulate microglia homeostasis that is crucial for regular cns development. also pivotal for brain development is the creation of tight junctions at the blood-brain barrier in order to control passage between the blood and brain. germ-free mice have increased blood-brain barrier permeability due to decreased expression of tight junction proteins occludin and claudin-5 as compared to normal gut microbiota mice. butyrate-producing bacteria and the dopamine metabolite 3,4-dihydroxyphenylacetic acid have been linked to higher quality of life indicators while γ-aminobutyric acid has been linked to higher levels of depression.