Research Article: High fat diet alters gut microbiota but not spatial working memory in early middle-aged Sprague Dawley rats

Date Published: May 29, 2019

Publisher: Public Library of Science

Author(s): Nikita Girish Deshpande, Juhi Saxena, Tristan G. Pesaresi, Casey Dylan Carrell, Grayson Breneman Ashby, Min-Ken Liao, Linnea Ruth Freeman, Andras Bilkei-Gorzo.


As the global population ages, and rates of dementia rise, understanding lifestyle factors that play a role in the development and acceleration of cognitive decline is vital to creating therapies and recommendations to improve quality of later life. Obesity has been shown to increase risk for dementia. However, the specific mechanisms for obesity-induced cognitive decline remain unclear. One potential contributor to diet-induced cognitive changes is neuroinflammation. Furthermore, a source of diet-induced inflammation to potentially increase neuroinflammation is via gut dysbiosis. We hypothesized that a high fat diet would cause gut microbe dysbiosis, and subsequently: neuroinflammation and cognitive decline. Using 7-month old male Sprague Dawley rats, this study examined whether 8 weeks on a high fat diet could impact performance on the water radial arm maze, gut microbe diversity and abundance, and microgliosis. We found that a high fat diet altered gut microbe populations compared to a low fat, control diet. However, we did not observe any significant differences between dietary groups on maze performance (a measure of spatial working memory) or microgliosis. Our data reveal a significant change to the gut microbiome without subsequent effects to neuroinflammation (as measured by microglia characterization and counts in the cortex, hippocampus, and hypothalamus) or cognitive performance under the parameters of our study. However, future studies that explore duration of the diet, composition of the diet, age of animal model, and strain of animal model, must be explored.

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The prevalence of obesity among US adults is above 36%, and has been rising significantly since the 1980s [1]. Diet is a significant lifestyle factor in the development of diabetes, hypertension, heart disease, and obesity. The Western Diet is characterized by high saturated fat, cholesterol and simple sugar content [2–4]. Alternatively, diets including fish, n-3 fatty acids, and a high ratio of polyunsaturated fatty acids to saturated fatty acids are associated with decreased risk for developing dementia [5]. Both epidemiological studies in humans and animal studies have begun to elucidate the potential effects of diet on cognition, and the mechanisms through which these effects occur. A comprehensive review of epidemiological studies of fat intake and cognition found support for the hypothesis that diets high in saturated fatty acids and trans-fatty acids are associated with higher risk of cognitive decline and dementia, whereas diets high in polyunsaturated fats or monounsaturated fats are associated with decreased risk for dementia [6].

The current study measured the change in gut microbes following consumption of a high-fat or control diet, performance on the water radial arm maze, and Iba-1 immunohistochemistry in three relevant brain regions. Contrary to our hypothesis, we observed changes to gut microbe populations without subsequent effects to neuroinflammation or working memory behavior.




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