Type 2 diabetes mellitus and obesity are associated with increased rates of depression, anxiety and other mood disorders. Furthermore, a diet that contains large quantities of fat can alter the gut microbiota by reducing bacterial diversity and modifying the microbial composition. In addition, research suggests that changes to the overall bacterial composition of the gut microbiota can induce systemic insulin resistance, which is notable for neuropsychiatric disorders as the brain is sensitive to fluctuations in serum levels of insulin.

Credit: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY/Getty

What remained unclear, however, was whether dietary changes and changes to the gut microbiota by antibiotics affected mood and behaviour and, more importantly, whether these changes to behaviour were mediated by changes in the microbiome in the gut. Now, C. Ronald Kahn and colleagues have reported that the modification of gut microbiota due to high-fat diet (HFD) feeding results in multiple behavioural abnormalities indicative of anxiety and depression in mice.

the modification of gut microbiota due to high-fat diet (HFD) feeding results in multiple behavioural abnormalities

To assess whether a link exists between the gut microbiota and brain function in the context of obesity, the authors fed mice a HFD with or without the addition of antibiotics that modify the microbiome independent of diet. Khan and colleagues then assessed the behaviour of the mice and tested whether changes in behaviour could be transferred to germ-free mice via the transfer of gut microbiota.

“We showed that a HFD induced changes in behaviour consistent with increased anxiety and depression,” explains Kahn. “These changes were reversed by antibiotic treatment that further modified the microbiome and the behaviours were transferable to germ-free mice.” The investigators also found that the behavioural changes in the mice were associated with changes in insulin signalling in the brain, as well as changes in neurotransmitters and metabolites in the blood that can affect brain function.

“Our current goal is to identify the metabolites that are produced by the microbiome that cause these behavioural changes,” concludes Khan. “If [we can achieve this], we can potentially use these metabolites to design new targets for treatment of anxiety and depressive disorders.”