The Role of the Gut Microbiome, Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders.

There is a growing recognition that both the gut microbiome and the immune system are involved in a number of psychiatric illnesses, including eating disorders. This should come as no surprise, given the important roles of diet composition, eating patterns, and daily caloric intake in modulating both biological systems. Here, we review the evidence that alterations in the gut microbiome and immune system may serve not only to maintain and exacerbate dysregulated eating behavior, characterized by caloric restriction in anorexia nervosa and binge eating in bulimia nervosa and binge eating disorder, but may also serve as biomarkers of increased risk for developing an eating disorder. We focus on studies examining gut dysbiosis, peripheral inflammation, and neuroinflammation in each of these eating disorders, and explore the available data from preclinical rodent models of anorexia and binge-like eating that may be useful in providing a better understanding of the biological mechanisms underlying eating disorders. Such knowledge is critical to developing novel, highly effective treatments for these often intractable and unremitting eating disorders.

Estradiol treatment attenuates high fat diet-induced microgliosis in ovariectomized rats.

Consumption of a high fat diet (HFD) increases circulating free fatty acids, which can enter the brain and promote a state of microgliosis, as defined by a change in microglia number and/or morphology. Most studies investigating diet-induced microgliosis have been conducted in male rodents despite well-documented sex differences in the neural control of food intake and neuroimmune signaling. This highlights the need to investigate how sex hormones may modulate the behavioral and cellular response to HFD consumption. Estradiol is of particular interest since it exerts a potent anorexigenic effect and has both anti-inflammatory and neuroprotective effects in the brain. As such, the aim of the current study was to investigate whether estradiol attenuates the development of HFD-induced microgliosis in female rats. Estradiol- and vehicle-treated ovariectomized rats were fed either a low-fat chow diet or a 60% HFD for 4 days, after which they were perfused and brain sections were processed via immunohistochemistry for microglia-specific Iba1 protein. Four days of HFD consumption promoted microgliosis, as measured via an increase in the number of microglia in the arcuate nucleus (ARC) of the hypothalamus and nucleus of the solitary tract (NTS), and a decrease in microglial branching in the ARC, NTS, lateral hypothalamus (LH), and ventromedial hypothalamus. Estradiol replacement attenuated the HFD-induced changes in microglia accumulation and morphology in the ARC, LH, and NTS. We conclude that estradiol has protective effects against HFD-induced microgliosis in a region-specific manner in hypothalamic and hindbrain areas implicated in the neural control of food intake.