Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances
AimChronic intermittent hypoxia (CIH) is a key characteristic of obstructive sleep apnea (OSA) syndrome, a chronic respiratory disorder. The mechanisms of CIH-induced metabolic disturbance and histopathological damage remain unclear.MethodsCIH-induced rats underwent daily 8-h CIH, characterized by o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1224396/full |
| _version_ | 1827382970565001216 |
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| author | Cong Li Song Shi |
| author_facet | Cong Li Song Shi |
| author_sort | Cong Li |
| collection | DOAJ |
| description | AimChronic intermittent hypoxia (CIH) is a key characteristic of obstructive sleep apnea (OSA) syndrome, a chronic respiratory disorder. The mechanisms of CIH-induced metabolic disturbance and histopathological damage remain unclear.MethodsCIH-induced rats underwent daily 8-h CIH, characterized by oxygen levels decreasing from 21% to 8.5% over 4 min, remaining for 2 min, and quickly returning to 21% for 1 min. The control rats received a continuous 21% oxygen supply. The levels of hypersensitive C reactive protein (h-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and nuclear factor kappa-B (NF-κB) were measured by ELISA. Histological analysis of the soft palates was conducted using HE staining. The microbial profiling of fecal samples was carried out by Accu16STM assay. Untargeted metabolomics of serum and soft palate tissue samples were analyzed by UPLC-MS. The protein expression of cAMP-related pathways in the soft palate was determined by Western blot.ResultsAfter 28 h of CIH induction, a significant increase in pro-inflammatory cytokines was observed in the serum, along with mucosal layer thickening and soft palate tissue hypertrophy. CIH induction altered the diversity and composition of fecal microbiota, specifically reducing beneficial bacteria while increasing harmful bacteria/opportunistic pathogens. Notably, CIH induction led to a significant enrichment of genera such as Dorea, Oscillibacter, Enteractinococcus, Paenibacillus, Globicatella, and Flaviflexus genera. Meanwhile, Additionally, CIH induction had a notable impact on 108 serum marker metabolites. These marker metabolites, primarily involving amino acids, organic acids, and a limited number of flavonoids or sterols, were associated with protein transport, digestion and absorption, amino acid synthesis and metabolism, as well as cancer development. Furthermore, these differential serum metabolites significantly affected 175 differential metabolites in soft palate tissue, mainly related to cancer development, signaling pathways, amino acid metabolism, nucleotide precursor or intermediate metabolism, respiratory processes, and disease. Importantly, CIH induction could significantly affect the expression of the cAMP pathway in soft palate tissue.ConclusionsOur findings suggest that targeting differential metabolites in serum and soft palate tissue may represent a new approach to clinical intervention and treatment of OSA simulated by the CIH. |
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| format | Article |
| id | doaj.art-969a99556f884f29b9b3d2f96458e5d5 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-08T14:31:10Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-969a99556f884f29b9b3d2f96458e5d52024-01-12T10:19:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-01-011410.3389/fendo.2023.12243961224396Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbancesCong LiSong ShiAimChronic intermittent hypoxia (CIH) is a key characteristic of obstructive sleep apnea (OSA) syndrome, a chronic respiratory disorder. The mechanisms of CIH-induced metabolic disturbance and histopathological damage remain unclear.MethodsCIH-induced rats underwent daily 8-h CIH, characterized by oxygen levels decreasing from 21% to 8.5% over 4 min, remaining for 2 min, and quickly returning to 21% for 1 min. The control rats received a continuous 21% oxygen supply. The levels of hypersensitive C reactive protein (h-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and nuclear factor kappa-B (NF-κB) were measured by ELISA. Histological analysis of the soft palates was conducted using HE staining. The microbial profiling of fecal samples was carried out by Accu16STM assay. Untargeted metabolomics of serum and soft palate tissue samples were analyzed by UPLC-MS. The protein expression of cAMP-related pathways in the soft palate was determined by Western blot.ResultsAfter 28 h of CIH induction, a significant increase in pro-inflammatory cytokines was observed in the serum, along with mucosal layer thickening and soft palate tissue hypertrophy. CIH induction altered the diversity and composition of fecal microbiota, specifically reducing beneficial bacteria while increasing harmful bacteria/opportunistic pathogens. Notably, CIH induction led to a significant enrichment of genera such as Dorea, Oscillibacter, Enteractinococcus, Paenibacillus, Globicatella, and Flaviflexus genera. Meanwhile, Additionally, CIH induction had a notable impact on 108 serum marker metabolites. These marker metabolites, primarily involving amino acids, organic acids, and a limited number of flavonoids or sterols, were associated with protein transport, digestion and absorption, amino acid synthesis and metabolism, as well as cancer development. Furthermore, these differential serum metabolites significantly affected 175 differential metabolites in soft palate tissue, mainly related to cancer development, signaling pathways, amino acid metabolism, nucleotide precursor or intermediate metabolism, respiratory processes, and disease. Importantly, CIH induction could significantly affect the expression of the cAMP pathway in soft palate tissue.ConclusionsOur findings suggest that targeting differential metabolites in serum and soft palate tissue may represent a new approach to clinical intervention and treatment of OSA simulated by the CIH.https://www.frontiersin.org/articles/10.3389/fendo.2023.1224396/fullobstructive sleep apneachronic intermittent hypoxiagut microbiotametabolomicscAMP pathway |
| spellingShingle | Cong Li Song Shi Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances Frontiers in Endocrinology obstructive sleep apnea chronic intermittent hypoxia gut microbiota metabolomics cAMP pathway |
| title | Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances |
| title_full | Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances |
| title_fullStr | Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances |
| title_full_unstemmed | Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances |
| title_short | Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances |
| title_sort | gut microbiota and metabolic profiles in chronic intermittent hypoxia induced rats disease associated dysbiosis and metabolic disturbances |
| topic | obstructive sleep apnea chronic intermittent hypoxia gut microbiota metabolomics cAMP pathway |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1224396/full |
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