論文 - 詳細
| RRC ID | 54363 |
|---|---|
| 著者 | Iatsenko I, Boquete JP, Lemaitre B. |
| タイトル | Microbiota-Derived Lactate Activates Production of Reactive Oxygen Species by the Intestinal NADPH Oxidase Nox and Shortens Drosophila Lifespan. |
| ジャーナル | Immunity |
| Abstract |
Commensal microbes colonize the gut epithelia of virtually all animals and provide several benefits to their hosts. Changes in commensal populations can lead to dysbiosis, which is associated with numerous pathologies and decreased lifespan. Peptidoglycan recognition proteins (PGRPs) are important regulators of the commensal microbiota and intestinal homeostasis. Here, we found that a null mutation in Drosophila PGRP-SD was associated with overgrowth of Lactobacillus plantarum in the fly gut and a shortened lifespan. L. plantarum-derived lactic acid triggered the activation of the intestinal NADPH oxidase Nox and the generation of reactive oxygen species (ROS). In turn, ROS production promoted intestinal damage, increased proliferation of intestinal stem cells, and dysplasia. Nox-mediated ROS production required lactate oxidation by the host intestinal lactate dehydrogenase, revealing a host-commensal metabolic crosstalk that is probably broadly conserved. Our findings outline a mechanism whereby host immune dysfunction leads to commensal dysbiosis that in turn promotes age-related pathologies. |
| 巻・号 | 49(5) |
| ページ | 929-942.e5 |
| 公開日 | 2018-11-20 |
| DOI | 10.1016/j.immuni.2018.09.017 |
| PII | S1074-7613(18)30432-1 |
| PMID | 30446385 |
| MeSH | Animals Carrier Proteins / genetics Carrier Proteins / metabolism Drosophila / physiology* Dysbiosis Gene Expression Intestinal Mucosa / immunology Intestinal Mucosa / metabolism Intestinal Mucosa / microbiology L-Lactate Dehydrogenase / genetics L-Lactate Dehydrogenase / metabolism Lactic Acid / metabolism* Longevity* Microbiota* Mutation NADPH Oxidases / genetics NADPH Oxidases / metabolism* Reactive Oxygen Species / metabolism* Signal Transduction Symbiosis |
| IF | 22.553 |
| 引用数 | 30 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 100 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | 5988R-1 5988R-3 |