Emily Soto Actions Download Free 18 High Quality
Modifications in gut microbial composition induced by diet and other factors can play an important role in the metabolic changes associated with obesity, including glucose intolerance, insulin resistance and inflammation in fat and liver [1, 2, 8, 11]. These interactions are complex and depend on multiple factors, such as host genetics; diet composition and quantity; presence of probiotics, prebiotics, or antibiotics; and other environmental factors [8, 10]. In the present study, we show that modification of gut microbiota due to HFD feeding of mice results in multiple behavioral abnormalities indicative of anxiety and depression. These include increased time spent in the dark compartment of a dark-light box, increased latency to feed in a novelty-suppressed feeding test, decreased exploration in an open-field test and increased marble burying activity. We show that antibiotic treatment improves not only the metabolic abnormalities induced by the HFD, but many of the behavioral changes associated with diet-induced obesity. Indeed, two weeks of treatment with either vancomycin or metronidazole reverses HFD-induced hyperglycemia and glucose intolerance (without affecting body weight) and corrects the depressive and anxiety-like behaviors. As 6 weeks on high-fat diet led to increased body weight gain compared to chow, it is not possible to separate the effect of mild diet-induced obesity (DIO) from the effects of the high-fat diet itself on behavior. However, antibiotic treatment did not lead to changes in food intake or body composition or block the HFD-induced weight gain, although it did reverse most of the behavioral changes. Thus, whether the behavioral changes in the HFD mice are due to the diet itself or mild obesity, the response to antibiotics indicates that they are, at least in part, due to the changing microbiome. This is further supported by the fact that the effect of HFD and antibiotics improvement could be reproduced in germ-free mice by fecal transfer of gut microbiota. Mechanistically, the improved behavioral tests are associated with a reversal of brain insulin resistance and signs of brain inflammation observed in DIO mice, as well as changes in brain metabolites, some neurotransmitters and the neurotrophic factor BDNF. Although vancomycin targets gram-positive bacteria, and metronidazole targets anaerobic bacteria, in the context of HFD-induced obesity, both antibiotics have similar effects on insulin signaling, inflammation, metabolism and behavior, suggesting the gut bacteria involved are sensitive to both antibiotics.
Emily Soto Actions Download Free 18
Taken together, our data indicate that modifications in gut microbiome of DIO mice drive changes in both host metabolism and host behavior. Indeed, HFD-fed mice develop central insulin resistance and altered behaviors indicative of anxiety and depression. Antibiotic treatment of HFD-fed mice, which causes major remodeling of the gut microbiome , improves peripheral and central insulin sensitivity, and reverses these behavioral/mood abnormalities. These effects are reversible when antibiotics are stopped and transferable to germ-free mice by cecal bacterial transfer. These effects of gut microbiota on the brain and behavior are mediated by changes in brain insulin signaling and inflammation, and by the modulation of neurotransmitters, metabolites and other neuroactive molecules, such as BDNF. Understanding these gut-brain interactions may open novel approaches to treatment of mood and behavioral disorders.