Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice
Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/11/12/1283 |
| _version_ | 1797503000255660032 |
|---|---|
| author | Larry D. Sanford Laurie L. Wellman Richard P. Ciavarra Edward C. Oldfield Rouzbeh Shams Jennifer L. Copare David A. Johnson |
| author_facet | Larry D. Sanford Laurie L. Wellman Richard P. Ciavarra Edward C. Oldfield Rouzbeh Shams Jennifer L. Copare David A. Johnson |
| author_sort | Larry D. Sanford |
| collection | DOAJ |
| description | Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axis. Male C57BL/6NCrl mice (4 to 5 per cage, fed standard lab chow) experienced SF via mechanical stimulation at 2 min intervals during the light (SF) and dark (DD, dark disturbances) periods. Home cage (HC) controls were undisturbed. After 10 days, fecal samples were collected at light onset, midday, light offset, and midnight. Samples were also collected after 10 days without SF. Subsequently, the mice were randomized across groups and allowed 20 additional days of recovery followed by 10 days of SF or DD. To assess effects on the microbiota, 16S rRNA sequencing was used, and mesenteric lymph nodes (MLNs) and cortex and medial prefrontal cortex were analyzed using cytokine arrays. SF and DD produced significant alterations in the microbiota compared to HC, and DD had greater impact than SF on some organisms. SF produced marked suppression in MLNs of chemokines that regulate inflammation (CCL3, CCL4 and their receptor CCR5) and maintain the immune mucosal barrier (Cxcl13) at the same time that cortical cytokines (IL-33) indicated neuroinflammation. DD effects on immune responses were similar to HC. These data suggest that SF alters the microbiome and suppresses mucosal immunity at the same time that mediators of brain inflammation are upregulated. The translational implications for potential application to clinical care are compelling. |
| first_indexed | 2024-03-10T03:44:13Z |
| format | Article |
| id | doaj.art-bfdde7f885c44cc294a840a3fb32cb67 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T03:44:13Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-bfdde7f885c44cc294a840a3fb32cb672023-11-23T09:13:14ZengMDPI AGLife2075-17292021-11-011112128310.3390/life11121283Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in MiceLarry D. Sanford0Laurie L. Wellman1Richard P. Ciavarra2Edward C. Oldfield3Rouzbeh Shams4Jennifer L. Copare5David A. Johnson6Sleep Research Laboratory, Center for Integrative Neuroscience and Inflammatory Diseases, Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USASleep Research Laboratory, Center for Integrative Neuroscience and Inflammatory Diseases, Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USAMicrobiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USAGastroenterology Division, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USAGastroenterology Division, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USAGastroenterology Division, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USAGastroenterology Division, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USABi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axis. Male C57BL/6NCrl mice (4 to 5 per cage, fed standard lab chow) experienced SF via mechanical stimulation at 2 min intervals during the light (SF) and dark (DD, dark disturbances) periods. Home cage (HC) controls were undisturbed. After 10 days, fecal samples were collected at light onset, midday, light offset, and midnight. Samples were also collected after 10 days without SF. Subsequently, the mice were randomized across groups and allowed 20 additional days of recovery followed by 10 days of SF or DD. To assess effects on the microbiota, 16S rRNA sequencing was used, and mesenteric lymph nodes (MLNs) and cortex and medial prefrontal cortex were analyzed using cytokine arrays. SF and DD produced significant alterations in the microbiota compared to HC, and DD had greater impact than SF on some organisms. SF produced marked suppression in MLNs of chemokines that regulate inflammation (CCL3, CCL4 and their receptor CCR5) and maintain the immune mucosal barrier (Cxcl13) at the same time that cortical cytokines (IL-33) indicated neuroinflammation. DD effects on immune responses were similar to HC. These data suggest that SF alters the microbiome and suppresses mucosal immunity at the same time that mediators of brain inflammation are upregulated. The translational implications for potential application to clinical care are compelling.https://www.mdpi.com/2075-1729/11/12/1283chemokinecytokineimmune systemmicrobiomeneuroinflammation |
| spellingShingle | Larry D. Sanford Laurie L. Wellman Richard P. Ciavarra Edward C. Oldfield Rouzbeh Shams Jennifer L. Copare David A. Johnson Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice Life chemokine cytokine immune system microbiome neuroinflammation |
| title | Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice |
| title_full | Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice |
| title_fullStr | Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice |
| title_full_unstemmed | Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice |
| title_short | Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice |
| title_sort | differential effect of light and dark period sleep fragmentation on composition of gut microbiome and inflammation in mice |
| topic | chemokine cytokine immune system microbiome neuroinflammation |
| url | https://www.mdpi.com/2075-1729/11/12/1283 |
| work_keys_str_mv | AT larrydsanford differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice AT laurielwellman differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice AT richardpciavarra differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice AT edwardcoldfield differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice AT rouzbehshams differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice AT jenniferlcopare differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice AT davidajohnson differentialeffectoflightanddarkperiodsleepfragmentationoncompositionofgutmicrobiomeandinflammationinmice |