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Concentration of short chain fatty acids produced by gut microbiota are related with cognitive dysfunction in a murine model of Alzheimer´s disease
1 , 1 , 1 , * 2
1  Departamento de Genética y Biología Molecular, Cinvestav Unidad Zacatenco. Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, CDMX Código Postal 07360. Ciudad de México Tel: +52 (55) 5747 3800.
2  Departamento de Farmacología, Cinvestav Unidad Zacatenco. Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, CDMX Código Postal 07360. Ciudad de México Tel: +52 (55) 5747 3800.

Abstract:

Introduction. Alzheimer´s disease (AD) is the most common dementia in aged population and is characterized by cognitive impairment and dysbiosis, not to mention amyloid plaques, neurofibrillary tangles and reactive gliosis as the main hallmarks in the brain. Currently, there is not an effective treatment against this condition. Recent reports have suggested an elevated abundance of pro-inflammatory bacteria in the gut microbiota (GM) of transgenic (Tg) AD models compared to wild type (WT) animals. Moreover, the short chain fatty acids (SCFAs) propionate and butyrate, produced by GM, have been reported as pro- and anti-inflammatory species respectively. Methods. In order to determine changes in GM diversity and SCFAs concentration related with cognitive impairment in AD pathology, we used 6 months-old WT and AD Tg male mice to evaluate working and spatial memory status utilizing T- and water-maze paradigms respectively, SCFAs (acetate, propionate and butyrate) concentration in feces using high performance liquid chromatography (HPLC), and GM diversity, enrichment and functional predictive metabolism by DNA sequencing. Results. We observed increases in the proportion of lactic acid bacterial taxa, and also in the concentration, proportion and predictive metabolism of propionate for Tg compared to WT mice. Acetate and butyrate fecal amounts, in addition to working and spatial memory scores, were decreased in Tg animals. Conclusions. Our data suggests lactic acid bacterial increases, acetate and butyrate reductions, and an enhanced propionate metabolism and production could be related with AD pathology. Further studies are need in order to attribute cognitive dysfunctions to these changes.

Keywords: Alzheimer; microbiota; propionate; butyrate; acetate; memory; neuroinflammation.
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