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Impact of dietary arachidonic acid intake on the gut microbiota and the gut-brain axis. Consequences for prevention of Alzheimer's disease by probiotics

Abstract : Alzheimer's disease (AD) is a neurodegenerative disease associated with aging, consisting of a major public health problem worldwide. There is currently no effective treatment or established preventions for this disease, highlighting the importance of the design of preventive strategies in the fight against this disease. Western diets are particularly rich in ω-6 fatty acids, especially arachidonic acid (ARA), which are converted into many inflammation mediators in the organism. Previous laboratory results have shown that dietary intake of ARA sensitizes mice to the neurotoxicity of Aβ peptide oligomers, the main agent of AD. In this thesis work, we studied the impact of this dietary intake of ARA on the fecal microbiota and the microbiota-gut-brain axis. For 9 to 12 weeks, three groups of 15 mice have consumed one of these 3 diets : a conventional murine diet (“Sdt-ARA” of 5% lipids), a moderately high-fat diet of 15% lipids including 31.9% of linoleic acid ("HL-ARA"), and a diet of 15% lipids including 25.3% linoleic acid and 6.6% ARA ("HL+ARA").Analysis of the fecal microbiota revealed that the "HL-ARA" diet promotes proliferation of the Bifidobacterium pseudolongum strain, which has been show to possess anti-inflammatory activities. Furthermore, the supply of ARA suppresses this proliferation by favouring Escherichia-Shigella multiplication (with potentiating effects on inflammation). A 3-to-11-fold increase in mRNA levels of the pro-inflammatory cytokines IL-1β and TNFα has been observed in the colon of mice fed with the "HL+ARA" diet. Enrichment of ARA led to an increase of the expression of other mediators of colon inflammation such as CD40, adiponectin, and ICAM-1, as well as the claudin 1 and occludin markers which are components of cellular tight junctions. Therefore, these changes in expression suggest that the integrity of the intestinal barrier has been compromised. Moreover, dietary intake of ARA led to a 10 fold increase in TNFα mRNA levels in mesenteric adipose tissue, while the impact on the liver was found to be much more moderate. At the cerebral level, a 9 weeks food intake of ARA led to a 1.5-1.8-fold increase in the protein level of GFAP in the hippocampus and the cortex, while no changes of the microglial marker Iba1 has not been reported. We also found decreased levels of IL-6 and TNFα mRNA in the global brain tissue.These results indicate that dietary intake of ARA induces low-grade systemic inflammation which may promote the expansion of an Alzheimer's-like process in the brain if an inducing signal occurs. As such, we also evaluated the impact of an innovative oral administration model of D-galactose, which has been described as an aging accelerator compound , leading to impairment of cognitive capacities, and the appearance of amyloid plaques in the mouse brains through elevated oxidative stress. We also studied the survival in the digestive tract of two strains of Streptococcus thermophilus with anti-inflammatory activity in vitro as reported by previous laboratory work, and of a strain of Lactobacillus plantarum capable of metabolizing ω-6 polyunsaturated fatty acids in conjugated fatty acids. This thesis work aims to assess the ability of these probiotic strains to fight against low-grade inflammation induced by dietary intake of ARAs and oxidative stress induced by D-galactose. New work is underway in the laboratory to investigate in more details all the biological processes at work in the different models and to determine the impact of probiotics on a combined administration of D-galactose and an ARA-enriched diet.
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Submitted on : Wednesday, April 6, 2022 - 2:48:59 PM
Last modification on : Thursday, April 7, 2022 - 3:31:06 AM


  • HAL Id : tel-03632777, version 1


Katleen Pinchaud. Impact of dietary arachidonic acid intake on the gut microbiota and the gut-brain axis. Consequences for prevention of Alzheimer's disease by probiotics. Food and Nutrition. Université de Lorraine, 2021. English. ⟨NNT : 2021LORR0190⟩. ⟨tel-03632777⟩



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