Reproductive aging drives deterministic microbiota assembly to mitigate uterine oxidative phosphorylation impairment via spermidine production in laying hens.
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Abstract
Background: Reproductive aging represents a critical physiological bottleneck characterized by a progressive decline in tissue homeostasis and physiological function. While the gut microbiota is known to shift during host aging, the ecological forces governing the assembly of the reproductive microbiota and its functional feedback on uterine homeostasis remain poorly understood.
Results: We demonstrated that uterine aging drives a transition from stochastic to deterministic microbial community assembly, selecting for a microbiota enriched in Rhodococcus in aged laying hens. Multi-omics analyses revealed that this deterministic shift acts as a compensatory mechanism to counteract age-related energy metabolism decline in the uterus. Mechanistically, the aged uterus suffered from oxidative phosphorylation impairment due to PARP1-mediated NAD+ depletion in response to accumulated DNA damage. However, the specific colonization of Rhodococcus ruber, or the administration of its metabolite spermidine, rescued this phenotype. Spermidine improved uterine energy metabolism by inducing PINK1/Parkin-mediated mitophagy, thereby restoring mitochondrial quality control and ATP production essential for eggshell biomineralization.
Conclusions: This study uncovers a previously unrecognized role of the microbiota in reproductive aging: resident microbes enhance oxidative phosphorylation in the aged uterus through the metabolite spermidine, which induces mitophagy. This process alleviates cellular energy deficiency caused by PARP1-mediated NAD + depletion, elucidating a key mechanism of host-microbe interaction in maintaining uterine energy homeostasis during aging. Video Abstract.
期刊介绍：
Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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