Characterization of fecal metabolome changes in patients with obstructive sleep apnea

Dong, Ying; Wang, Pan; Lin, Junling; Han, Chide; Jiao, Jie; Zuo, Kun; Chen, Mulei; Yang, Xinchun; Cai, Jun; Jiang, He; Guo, Xiaojuan; Li, Jing

doi:10.5664/jcsm.9668

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…The importance of plasma long-chain fatty acid levels (especially arachidonic acid) as an important assessment was emphasized in an investigation of the interaction between sleep quality, stress, depressive symptoms, and polyunsaturated fatty acid status in hypertensive patients (32). In addition, a 180-day, single-center, randomized, double-blind, placebo-controlled trial showed that depressed children taking docosahexaenoic acid (DHA) + arachidonic acid (AA) supplements had signi cantly improved sleep compared to the group with placebo (33). Another study observed reduced arachidonic acid levels in fecal samples from patients with obstructive sleep apnea (OSA) (34).…”

Section: Discussionmentioning

confidence: 99%

Causal Effects of 1400 Blood Metabolites And Sleep Disorders: A Mendelian Randomization Study

ma,

min,

huanghong

et al. 2024

Preprint

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Background: There is growing evidence that sleep disorders (SD) affect changes in the body's metabolic microbiota, such as serum levels of glucose, lipid metabolites, insulin, adrenaline, and cortisol, which are all modified by sleep. However, the causal relationship between these serum metabolites and SD remains undetermined. Methods: A comprehensive two-sample Mendelian randomization (MR) study was performed to investigate the causal relationship between blood microbiota characteristics and SD. Additionally, reverse MR analyses were performed to mitigate the effects of reverse causality, genetic correlation, and linkage disequilibrium (LD). Moreover, the screened significant metabolites were further examined in an additional dataset. Finally, potential metabolic pathways associated with SD were exposed by enrichment analysis. Results: In a survey of 1400 metabolites, 201 exhibited statistical significance (P<0.05) in an inverse variance weighted (IVW) model. Among these, 18 known metabolites and four unknown metabolites were found to be significantly associated with SD (PFDR<0.05), with six of them being validated in the validation set. Enrichment analysis revealed the involvement of five typical metabolites in 23 central metabolic pathways (P<0.05). Notably, glycine, D-lysine, cyclic adenosine monophosphate, guanosine, and arachidonic acid could serve as key markers based on their roles in the pathways, disease characterization prediction, and localization. Furthermore, inverse Mendelian randomization analysis indicated that six known metabolites and three unknown metabolites were significantly associated with SD (PFDR<0.2), and these metabolites were implicated in 15 core metabolic pathways (P<0.05). Among them, cortisone, cortisol, N-acetyl-L-aspartic acid, and arachidonic acid played crucial roles. These findings provide novel insights for early screening, prevention, and treatment of SD. Conclusions:This study reveals the potential relationship between blood microbiota and SD using a two-sample Mendelian randomization approach, and the findings provide new insights into the role of genetic exposure interactions in the development of SD.

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Section: Discussionmentioning

confidence: 99%

Causal Effects of 1400 Blood Metabolites And Sleep Disorders: A Mendelian Randomization Study

ma,

min,

huanghong

et al. 2024

Preprint

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“…FBAP7 knock-out mice displayed an increase in wake during the light phase, indicating that FBAP7 is required for normal sleep inhibition [ 51 ]. More recently, it was reported that a reduction in stearic acid was observed in stool samples from patients with obstructive sleep apnea disease [ 52 ], which indicates that stearic acid may play an important role in controlling sleep. In particular, one additional ZSSG ingredient examined in the current study is pregnane xenobiotic receptor (PXR, NR1I2).…”

Section: Discussionmentioning

confidence: 99%

Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture

Ren,

Wu,

Wang

et al. 2023

Chin Med

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Background Ziziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement. Methods Mice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients. Results ZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model (P < 0.05). ZSSG significantly enhanced the brain content of GABA in mice. Furthermore, ZSSG also significantly decreased sleep latency-induced by sodium barbital in mice (P < 0.05). Metabolic analysis revealed significant differences in 10 metabolites between ZSSG group and the groups administering ZSS or GABA. Lastly, using the network-based ingredient screening model, we discovered potential four active ingredients and three pairwise ingredient combinations with synergistic effect on insomnia from ZSSG among 85 ingredients identified by UPLC-Q/TOF–MS. Also, we have constructed an online computation platform. Conclusion Our data demonstrated that ZSSG improved the sleeping quality of mice and helped to balance metabolic disorders-associated with sleep disorders. Moreover, based on the network-based prediction method, the four potential active ingredients in ZSSG could serve as quality markers-associated with insomnia. The network-based framework may open up a new avenue for the discovery of active ingredients of herbal medicine for treating complex chronic diseases or symptoms, such as insomnia.

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“…The fecal metabolome provides a functional readout of the gut microbiome and its interactions with the host [ 63 ]. Accordingly, fecal metabolomic features accurately discriminate between OSA patients and healthy controls and are associated with OSA severity [ 64 ].…”

Section: Altered Gut Microbiome In Osa: Implications For Hypertension...mentioning

confidence: 99%

Is the Gut Microbiome Implicated in the Excess Risk of Hypertension Associated with Obstructive Sleep Apnea? A Contemporary Review

et al. 2023

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Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder and an established risk factor for cardiovascular diseases, including hypertension. The pathogenesis of elevated blood pressure (BP) in OSA is multifactorial, including sympathetic overdrive, vascular aberrations, oxidative stress, inflammation, and metabolic dysregulation. Among the mechanisms potentially involved in OSA-induced hypertension, the role of the gut microbiome is gaining increasing attention. Perturbations in the diversity, composition, and function of the gut microbiota have been causally linked to numerous disorders, and robust evidence has identified gut dysbiosis as a determinant of BP elevation in various populations. In this brief review, we summarize the current body of literature on the implications of altered gut microbiota for hypertension risk in OSA. Data from both preclinical models of OSA and patient populations are presented, and potential mechanistic pathways are highlighted, along with therapeutic considerations. Available evidence suggests that gut dysbiosis may promote the development of hypertension in OSA and may thus be a target for interventions aimed at attenuating the adverse consequences of OSA in relation to cardiovascular risk.

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Characterization of fecal metabolome changes in patients with obstructive sleep apnea

Cited by 8 publications

References 51 publications

Causal Effects of 1400 Blood Metabolites And Sleep Disorders: A Mendelian Randomization Study

Causal Effects of 1400 Blood Metabolites And Sleep Disorders: A Mendelian Randomization Study

Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture

Is the Gut Microbiome Implicated in the Excess Risk of Hypertension Associated with Obstructive Sleep Apnea? A Contemporary Review

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