The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut
The gut microbiome plays a key role in the maintenance of host metabolic homeostasis and health. Most metabolic processes cycle with a 24-hour rhythm, but the extent to which the microbiome influences metabolite cycling under different conditions, such as variations in dietary composition, remains l...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/97130 |
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| author | Yueliang Zhang Sara B Noya Yongjun Li Jichao Fang Amita Sehgal |
| author_facet | Yueliang Zhang Sara B Noya Yongjun Li Jichao Fang Amita Sehgal |
| author_sort | Yueliang Zhang |
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| description | The gut microbiome plays a key role in the maintenance of host metabolic homeostasis and health. Most metabolic processes cycle with a 24-hour rhythm, but the extent to which the microbiome influences metabolite cycling under different conditions, such as variations in dietary composition, remains largely unknown. In this study, we utilized high temporal resolution metabolite profiling of the Drosophila gut to investigate the role of the microbiome in metabolite cycling. We find that the microbiome increases the number of oscillating metabolites despite the previous finding that it dampens transcript cycling in the gut. Time-restricted feeding also promotes metabolite cycling and does so to a larger extent in germ-free flies, thereby increasing cycling in these flies to levels comparable to those in microbiome-containing flies. Enhancement of cycling by the microbiome depends upon a circadian clock, which also maintains phase in the face of changes in the microbiome. Interestingly, a high protein diet increases microbiome-dependent metabolite cycling, while a high sugar diet suppresses it. Gene Ontology identifies amino acid metabolism as the metabolic pathway most affected by changes in the gut microbiome, the circadian clock, and timed feeding, suggesting that it is subject to regulation by multiple inputs. Collectively, our observations highlight a key role of the gut microbiome in host metabolite cycling and reveal a complex interaction with internal and external factors. |
| format | Article |
| id | doaj-art-e3a9ea8731b8474c8ce7b007bf0ad448 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-e3a9ea8731b8474c8ce7b007bf0ad4482025-08-20T03:28:32ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011310.7554/eLife.97130The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gutYueliang Zhang0Sara B Noya1Yongjun Li2Jichao Fang3Amita Sehgal4https://orcid.org/0000-0001-7354-9641HHMI, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, ChinaHHMI, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesHHMI, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesInstitute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, ChinaHHMI, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesThe gut microbiome plays a key role in the maintenance of host metabolic homeostasis and health. Most metabolic processes cycle with a 24-hour rhythm, but the extent to which the microbiome influences metabolite cycling under different conditions, such as variations in dietary composition, remains largely unknown. In this study, we utilized high temporal resolution metabolite profiling of the Drosophila gut to investigate the role of the microbiome in metabolite cycling. We find that the microbiome increases the number of oscillating metabolites despite the previous finding that it dampens transcript cycling in the gut. Time-restricted feeding also promotes metabolite cycling and does so to a larger extent in germ-free flies, thereby increasing cycling in these flies to levels comparable to those in microbiome-containing flies. Enhancement of cycling by the microbiome depends upon a circadian clock, which also maintains phase in the face of changes in the microbiome. Interestingly, a high protein diet increases microbiome-dependent metabolite cycling, while a high sugar diet suppresses it. Gene Ontology identifies amino acid metabolism as the metabolic pathway most affected by changes in the gut microbiome, the circadian clock, and timed feeding, suggesting that it is subject to regulation by multiple inputs. Collectively, our observations highlight a key role of the gut microbiome in host metabolite cycling and reveal a complex interaction with internal and external factors.https://elifesciences.org/articles/97130microbiomecircadian rhythmmetabolite cycling |
| spellingShingle | Yueliang Zhang Sara B Noya Yongjun Li Jichao Fang Amita Sehgal The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut eLife microbiome circadian rhythm metabolite cycling |
| title | The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut |
| title_full | The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut |
| title_fullStr | The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut |
| title_full_unstemmed | The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut |
| title_short | The microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the Drosophila gut |
| title_sort | microbiome interacts with the circadian clock and dietary composition to regulate metabolite cycling in the drosophila gut |
| topic | microbiome circadian rhythm metabolite cycling |
| url | https://elifesciences.org/articles/97130 |
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