Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice

Abstract

Alzheimer’s disease is characterized by cognitive dysfunction and aging is an important predisposing factor; however, the pathological and therapeutic mechanisms are not fully understood. Recently, the role of gut microbiota in Alzheimer’s disease has received increasing attention. The cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice was significantly decreased and the Chao 1 and Shannon indices, principal coordinates analysis, and principal component analysis results were notably abnormal compared with that of those in senescence-accelerated mouse resistant 1 (SAMR1) mice. Moreover, 27 gut bacteria at six phylogenetic levels differed between SAMP8 and SAMR1 mice. In a separate study, we transplanted fecal bacteria from SAMP8 or SAMR1 mice into pseudo germ-free mice. Interestingly, the pseudo germ-free mice had significantly lower cognitive function prior to transplant. Pseudo germ-free mice that received fecal bacteria transplants from SAMR1 mice but not from SAMP8 mice showed improvements in behavior and in α-diversity and β-diversity indices. In total, 14 bacteria at six phylogenetic levels were significantly altered by the gut microbiota transplant. These results suggest that cognitive dysfunction in SAMP8 mice is associated with abnormal composition of the gut microbiota. Thus, improving abnormal gut microbiota may provide an alternative treatment for cognitive dysfunction and Alzheimer’s disease.

Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse

“…Furthermore, APP/PS1 mice had significantly higher alpha-diversity compared to control animals at 8 months of age in a study by Harach et al (2017). In the senescence accelerated mouse prone 8 (SAMP8) model of AD, alpha diversity was significantly lower in 7-month old SAMP8 mice as compared to age-matched controls (Zhan et al, 2018). While differences in the mouse models of AD and experimental designs might be partly responsible for these conflicting results, the true association between alpha diversity of the gut microbiome and AD still needs to be elucidated.…”

“…The link between AD and alterations in the gut microbiome composition has already been established in several experimental animal models (Brandscheid et al, 2017;Harach et al, 2017;Shen et al, 2017;Zhang et al, 2017;Bauerl et al, 2018;Peng et al, 2018;Zhan et al, 2018) and clinical studies (Cattaneo et al, 2017;Vogt et al, 2017;Zhuang et al, 2018). However, the exact causal mechanism is still not understood.…”

Fecal Microbiota Transplantation in Neurological Disorders

“…FMT studies in animal models ( Table 8) Zhan et al (2018) observed that wild-type mice showed decreased cognitive function after broad-spectrum antibiotic treatment. Subsequently, spatial learning and memory improved after receiving feces from senescence-resistant mice (similar to control) compared to mice receiving feces from senescenceprone mice (similar to antibiotics plus vehicle).…”

Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve

“…Based on previous reports [13,15,24,25], broad-spectrum antibiotics (ampicillin 1 g/L, neomycin sulfate 1 g/L, metronidazole 1 g/L, Sigma-Aldrich Co. Ltd, St. Louis, MO, USA) dissolved in drinking water were given ad libitum to male C57BL/6 mice for 14 consecutive days (days 1-14). The drinking solution was renewed every 2 days.…”