Inflammation and gut microbiota contribute to the cognitive deficits induced by cafeteria diet

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Embargoed until 2022-04-01
Copyright: Leigh, Sarah-Jane
Abstract
Diets rich in saturated fat and sugar impair hippocampal-dependent cognition in both humans and rodents. Two potential mechanisms underlying this diet-induced cognitive dysfunction are inflammation and gut microbiome composition. Work described in this thesis investigated the effects of interventions targeting these mechanisms using male Sprague-Dawley rats fed a high-fat, high-sugar western-style cafeteria diet. Rats fed this diet exhibited impaired spatial recognition memory, metabolic disturbances and faecal microbiome alterations, including reductions in relative Lactobacillus abundance. These rats exhibited consistent upregulation of pro-inflammatory Il6 gene expression in white adipose tissue, with less consistent changes observed in the expression of other cytokines and toll-like receptors. Cafeteria diet increased Aif1 expression in the dorsal hippocampus across all studies, with less consistent upregulation of Il6 and Gfap gene expression. The studies in Chapter 3 examined whether co-administration of the antibiotic and anti-inflammatory drug minocycline prevented diet-induced cognitive impairment across six weeks exposure, while Chapter 4 examined the effects of minocycline implementation after diet-induced cognitive impairment had been established. Minocycline both prevented and reversed cognitive impairment and hippocampal pro-inflammatory gene upregulation in cafeteria-fed rats, while impairing cognition and increasing pro-inflammatory gene expression in chow-fed controls. Minocycline treatment and cafeteria diet independently altered faecal microbiome composition, and Desulfovibrio piger abundance was significantly associated with spatial recognition memory in both protocols. A pilot study (Chapter 5) extended these findings by treating cafeteria-fed rats with a targeted Lactobacillus probiotic based on the species depleted by cafeteria diet. This treatment alleviated the diet-induced impairments in spatial recognition memory. These findings were extended by the study described in Chapter 6 which showed that the probiotic transiently prevented cafeteria diet-induced cognitive impairment while altering gut microbiome composition and white adipose gene expression. In summary, interventions targeting the microbiome restored cognition in cafeteria-fed rats. However, the probiotic benefits were transient, and minocycline caused adverse outcomes in healthy controls. These results overall highlight the fundamental role of inflammation and gut microbiome composition in cafeteria diet-induced cognitive impairment and provide new insight into the interconnectedness of inflammatory processes and microbiota responses to dietary interventions.
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Author(s)
Leigh, Sarah-Jane
Supervisor(s)
Morris, Margaret
Westbrook, R Frederick
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Publication Year
2019
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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