AUTHOR=Bi Tingting , Zhang Lijing , Zhan Libin , Feng Ruiqi , Zhao Tian , Ren Weiming , Hang Tianyi , Zhou Wen , Lu Xiaoguang TITLE=Integrated Analyses of Microbiomics and Metabolomics Explore the Effect of Gut Microbiota Transplantation on Diabetes-Associated Cognitive Decline in Zucker Diabetic Fatty Rats JOURNAL=Frontiers in Aging Neuroscience VOLUME=14 YEAR=2022 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.913002 DOI=10.3389/fnagi.2022.913002 ISSN=1663-4365 ABSTRACT=

Diabetes-associated cognitive decline (DACD), one of the complications of type 2 diabetes (T2DM), correlates significantly with the disorder in glycolipid metabolism, insulin/leptin resistance, and accumulation of β-amyloid (Aβ). Although gut microbiota transplantation (GMT), a novel non-invasive physiotherapy strategy, has been a promising intervention to alleviate the symptoms of T2DM, its protective effect on progressive cognitive decline remains elusive. Here, we transplanted the gut microbiota of healthy or cognitive decline donor rats into ZDF or LZ rats, and integrated microbiomics and metabolomics to evaluate the directional effect of the gut microbiota on the recipient rats. The basal metabolism phenotype changed in ZDF rats instead of in LZ rats. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, stimulate the brain insulin and leptin signaling pathways, and regulate the deposition of Aβ in the brain. It is worth noting that 10 species of genera, such as Parabacteroides, Blautia, and Lactobacillus, can regulate 20 kinds of metabolites, such as propanoic acid, acetic acid, and citramalic acid, and having a significant improvement on the cognitive behavior of ZDF rats. In addition, the correlation analysis indicated the gut microbiota and metabolites are highly associated with host phenotypes affected by GMT. In summary, our study indicates that altering the microbiota-gut-brain axis by reshaping the composition of gut microbiota is a viable strategy that has great potential for improving cognitive function and combatting DACD.