ABSTRACT
Background: Growing evidence has well documented the close association between the gut microbiome and allergic respiratory disease, which has been notably represented by allergic asthma. However, it is unclear whether this association is a causal link. Therefore, we investigated the potential causal associations between the gut microbiome and allergic asthma or other allergic diseases. Methods: In this study, we performed two-sample Mendelian randomization (MR) analyses by using the publicly available genome-wide association study (GWAS) summary data. Single-nucleotide polymorphisms (SNPs) that significantly correlated were selected as instrumental variables. The inverse variance weighted (IVW) method was used to examine the potential causal gut microbial genera for allergic asthma and other allergic diseases. The robustness of the primary findings of the MR analyses was ensured by using different sensitivity analyses. Results: Combining the findings from multiple analyses, the host genetic-driven increases in Butyricimonas at the genus level were positively correlated with the risk of allergic asthma. In addition, phylum Bacteroidetes and class Bacteroidia were also found to have negative associations with the risk of allergic asthma; genus Slackia was identified as having potential causal effects with allergic asthma. No clear evidence of pleiotropy and heterogeneity was observed in genus Butyricimonas. Butyricimonas was also found to have an association with allergic rhinitis, but not with other allergic diseases. Conclusion: Our findings indicate that there are new gut microbial genera that were causally associated with the risk of allergic asthma and other allergic diseases, and offer novel insights into the pathogenesis of allergic respiratory diseases.
ABSTRACT
OBJECTIVE: Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. RESEARCH DESIGN AND METHODS: Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aß aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. RESULTS: Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aß aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. CONCLUSIONS: Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.
