Academic Journal
Intestinal endogenous metabolites affect neuroinflammation in 5×FAD mice by mediating 'gut-brain' axis and the intervention with Chinese Medicine
| Title: | Intestinal endogenous metabolites affect neuroinflammation in 5×FAD mice by mediating 'gut-brain' axis and the intervention with Chinese Medicine |
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| Authors: | Xinru Gu, Miaoxuan Fan, Yanyan Zhou, Yan Zhang, Linna Wang, Wenya Gao, Tao Li, Hongjie Wang, Nan Si, Xiaolu Wei, Baolin Bian, Haiyu Zhao |
| Source: | Alzheimer’s Research & Therapy, Vol 16, Iss 1, Pp 1-18 (2024) |
| Publisher Information: | BMC, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry LCC:Neurology. Diseases of the nervous system |
| Subject Terms: | Alzheimer’s disease (AD), Neuroinflammation, Short-chain fatty acid (SCFA), Gut microbiome, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: | Abstract Background Emerging evidence suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression. However, it remained unclear how the gut microbiome and neuroinflammation in the brain mutually interact or how these interactions affect brain functioning and cognition. Here we hypothesized that “gut-brain” axis mediated by microbial derived metabolites was expected to novel breakthroughs in the fields of AD research and development. Methods Multiple technologies, such as immunofluorescence, 16s rDNA sequencing, mass spectrometry-based metabolomics (LC-QQQ-MS and GC-MS), were used to reveal potential link between gut microbiota and the metabolism and cognition of the host. Results Microbial depletion induced by the antibiotics mix (ABX) verified that “gut-brain” can transmit information bidirectionally. Short-chain fatty acid-producing (SCFAs-producing) bacteria and amino acid-producing bacteria fluctuated greatly in 5×FAD mice, especially the reduction sharply of the Bifidobacteriaceae and the increase of the Lachnospiraceae family. Concentrations of several Tryptophan-kynurenine intermediates, lactic acid, CD4+ cell, and CD8+ cells were higher in serum of 5×FAD mice, whilst TCA cycle intermediates and Th1/Th2 were lower. In addition, the levels of iso-butyric acid (IBA) in feces, serum, and brain of 5×FAD mice were increased compared with WT-M mice, especially in serum. And IBA in the brain was positively correlated with Aβ and proinflammatory factors. Conclusion Together, our finding highlighted that the alternation in gut microbiota affected the effective communication between the “gut-brain” axis in 5×FAD mice by regulating the immune system, carbohydrate, and energy metabolism. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1758-9193 |
| Relation: | https://doaj.org/toc/1758-9193 |
| DOI: | 10.1186/s13195-024-01587-5 |
| Access URL: | https://doaj.org/article/fcddb19fdfe64895836e9e6fcda5e2c0 |
| Accession Number: | edsdoj.fcddb19fdfe64895836e9e6fcda5e2c0 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 17589193 |
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| DOI: | 10.1186/s13195-024-01587-5 |
| Published in: | Alzheimer’s Research & Therapy |
| Language: | English |