Dataset Information

Contribution of Gut Microbiota to Immunological Changes in Alzheimer's Disease.

ABSTRACT: Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer's disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.

SUBMITTER: van Olst L

PROVIDER: S-EPMC8200826 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Contribution of Gut Microbiota to Immunological Changes in Alzheimer's Disease.

van Olst Lynn L Roks Sigrid J M SJM Kamermans Alwin A Verhaar Barbara J H BJH van der Geest Anne M AM Muller Majon M van der Flier Wiesje M WM de Vries Helga E HE

Frontiers in immunology 20210531

Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer's disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature o ...[more]

PMID: 34135909

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Project description:Gut microbiota dysbiosis plays a significant role in the progression of liver disease, and no effective drugs are available for the full spectrum. In this study, we aimed to explore the dynamic changes of gut microbiota along the liver disease spectrum, together with the changes in cognition and brain metabolism. Sprague-Dawley rats were divided into four groups reflecting different stages of liver disease: control diet (NC); high-fat, high-cholesterol diet (HFHC), emulating non-alcoholic steatohepatitis; control diet + thioacetamide (NC + TAA), simulating acute liver failure; and high-fat, high-cholesterol diet + thioacetamide (HFHC + TAA) to assess the effect of the superimposed damages. The diet was administered for 14 weeks and the thioacetamide was administrated (100 mg/kg day) intraperitoneally over 3 days. Our results showed changes in plasma biochemistry and liver damage across the spectrum. Differences in gut microbiota at the compositional level were found among the experimental groups. Members of the Enterobacteriaceae family were most abundant in HFHC and HFHC + TAA groups, and Akkermansiaceae in the NC + TAA group, albeit lactobacilli genus being dominant in the NC group. Moreover, harm to the liver affected the diversity and bacterial community structure, with a loss of rare species. Indeed, the superimposed damage group (HFHC + TAA) suffered a loss of both rare and abundant species. Behavioral evaluation has shown that HFHC, NC + TAA, and HFHC + TAA displayed a worsened execution when discriminating the new object. Also, NC + TAA and HFHC + TAA were not capable of recognizing the changes in place of the object. Furthermore, working memory was affected in HFHC and HFHC + TAA groups, whereas the NC + TAA group displayed a significant delay in the acquisition. Brain oxidative metabolism changes were observed in the prefrontal, retrosplenial, and perirhinal cortices, as well as the amygdala and mammillary bodies. Besides, groups administered with thioacetamide presented an increased oxidative metabolic activity in the adrenal glands. These results highlight the importance of cross-comparison along the liver spectrum to understand the different gut-microbiota-brain changes. Furthermore, our data point out specific gut microbiota targets to design more effective treatments, though the liver-gut-brain axis focused on specific stages of liver disease.

Dataset Information

Contribution of Gut Microbiota to Immunological Changes in Alzheimer's Disease.

Publications

Contribution of Gut Microbiota to Immunological Changes in Alzheimer's Disease.

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