With regards sphingomyelins, MET mice displayed increased levels of SM OH C, SM OH C: and SM C; while, conversely, PKF mice showed reduced levels of the latter two metabolites. MET mice were found to have increased levels of PC ae C: and decreased PC ae C. Finally, the two therapeutics acted conversely with regards acylcarnitine entities.PKF mice displayed increased levels of hexadecenoylcarnatine; while MET mice presented with reduced levels of tetradecanoylcarnatine. Dorea relative abundance was positively Targetmol’s Acetaldehyde,Acetaldehyde correlated with several acylcarnitines, and negatively correlated with a range of phosphatidylcholines and a single sphingomyelin. While we acknowledge the major impact that diet imposes on our gut microbiome, until recently, little consideration had been given to the potential impact that the thousands of regularly prescribed oral medications may have on this plastic enteric ecosystem.In line with this, we set out to assess the effect of a novel DPP inhibitor on the gut microbiota composition of metabolically dysfunctional mice.In addition, our objectives extended to directly compare these effects with those of metformin, in order to assess whether such alterations may be the result of metabolism correction, or rather if they are therapy specific.Finally, we examined the downstream effects of both therapeutics on several classes of potentially metabolically important host plasma metabolites.Metformin remains a firstline therapeutic in the management of TDM, acting in part through the suppression of hepatic gluconeogenesis and promotion of insulin sensitivity. In line with this, MET mice in the present study displayed increased insulin sensitivity and improved cholesterol handling, with reduced weight gain and mesenteric adiposity.The vildagliptin analogue PKF is a DPP inhibitor and therefore confers its beneficial effects by extending the halflife of endogenous GLP.Consistent with this, PKF animals demonstrated improved cholesterol metabolism, a trend towards improved glucose handling and reduced mesenteric adipose tissue.These physiological changes are, for the most part, in line with the expected outcomes for each metabolic parameter, suggesting that the therapeutics functioned reasonably well in this animal model of metabolic dysfunction.Already mentioned, the administration of metformin to both animal and man has been shown to alter the composition of the gut microbiota with potency, and is rivalled in the consistency of these effects only by antibiotic regimes.In the current study and animal model of metabolic dysfunction, metformin produced many of the same effects which have been demonstrated previously, thereby reiterating this consistency.The results of this smallscale phase I trial are eagerly awaited.Curiously, metformin appeared to drastically reduce the gut microbiota diversity of obese mice, an effect which has been reported previously in rodents. This result initially appears paradoxical in light of current knowledge, as microbiota diversity and gene richness have been found to associate tightly with metabolic fitness in human cohorts. In fact, the antimicrobial attributes of metformin are now a topic of discussion having been demonstrated against several common pathogens in vitro. In addition, metformin therapy is often associated with adverse gastrointestinal tract symptoms, with up to a quarter of patients experiencing bloating, nausea or diarrhoea. It may be of interest to stratify clinical patients on metformin monotherapy that are symptomatic and nonsymptomatic of gastrointestinal symptoms and to examine the composition of the gut microbiota to assess whether this may be microbiallymediated.