Abstract
The aim of this research was to test the hypothesis that changes in the intestinal microbiota lead to the alternation of histidine metabolism and Th17/Treg cell imbalance in obstructive sleep apnea (OSA) patients. In total, 46 subjects were enrolled in the study, with 32 subjects in the OSA group and 14 in the healthy group, according to polysomnography examinations. Basic clinical characteristics were collected for this analysis. Feces were collected from OSA patients to detect the gut microbiota using 16S rRNA sequencing. Peripheral blood was obtained to detect the Th17/Treg cell ratio by flow cytometry. The present research demonstrated that at the phylum level, OSA patients have a disproportionate Firmicutes/Bacteroidetes ratio with increased Firmicutes and decreased Bacteroidetes in the gut microbiota compared to the healthy population. A Metastats analysis also indicated that the family Rikenellaceae was prevalent in the control group but not the OSA group. In addition, the abundance of Clostridium_XlVa was reduced and the abundance of Alistipes was elevated in healthy subjects at the genus level. Furthermore, a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis identified the alternation of metabolic pathways in OSA patients. The current study also identified an imbalance of Th17/Treg cells in OSA patients, with OSA patients having an elevated number of Treg cells compared to the control group. We determined that the abundance of Rikenellaceae and Alistipes increased and Clostridium_XlVa decreased in patients with OSA, which may have caused an imbalance in the proportion of Th17/Treg cells.
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The datasets used and analysed during the current study available from the corresponding author on reasonable request.
Change history
14 May 2022
A Correction to this paper has been published: https://doi.org/10.1007/s00203-022-02951-5
References
Anderson ME Jr, Buchwald ZS, Ko J, Aurora R, Sanford T (2014) Patients with pediatric obstructive sleep apnea show altered T-cell populations with a dominant TH17 profile. Otolaryngol Head Neck Surg 150:880–886. https://doi.org/10.1177/0194599814521780
Badran M, Ayas N, Laher I (2014) Insights into obstructive sleep apnea research. Sleep Med 15:485–495. https://doi.org/10.1016/j.sleep.2014.01.009
Berry RB et al (2012) Rule for Scoring Respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 8:597–619. https://doi.org/10.5664/jcsm.2172
Durgan DJ et al (2016) Role of the gut microbiome in obstructive sleep apnea-induced hypertension. Hypertension 67:469–474. https://doi.org/10.1161/HYPERTENSIONAHA.115.06672
Furusawa Y et al (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–450. https://doi.org/10.1038/nature12721
Ganesh BP et al (2018) Prebiotics, probiotics, and acetate supplementation prevent hypertension in a model of obstructive sleep apnea. Hypertension 72:1141–1150. https://doi.org/10.1161/HYPERTENSIONAHA.118.11695
Jialing L et al (2020) Changes in serum inflammatory cytokine levels and intestinal microbiota in a self-healing dextran sodium sulfate-induced ulcerative colitis murine model. Life Sci 263:118587. https://doi.org/10.1016/j.lfs.2020.118587
Ko CY et al (2019) Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities. Clin Sci (lond) 133:905–917. https://doi.org/10.1042/CS20180891
Li Z et al (2016) Efficacy of nasal continuous positive airway pressure on patients with OSA with erectile dysfunction and low sex hormone levels. Respir Med 119:130–134. https://doi.org/10.1016/j.rmed.2016.09.0019
Lucking EF et al (2018) Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs. EBioMedicine 38:191–205. https://doi.org/10.1016/j.ebiom.2018.11.010
Mashaqi S, Gozal D (2019) Obstructive sleep apnea and systemic hypertension: gut dysbiosis as the mediator? J Clin Sleep Med 15:1517–1527. https://doi.org/10.5664/jcsm.7990
Matsushita M et al (2021) Gut microbiota-derived short-chain fatty acids promote prostate cancer growth via IGF1 signaling. Cancer Res 81:4014–4026. https://doi.org/10.1158/0008-5472.CAN-20-4090
Moreno-Indias I et al (2015) Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J 45:1055–1065. https://doi.org/10.1183/09031936.00184314
Moreno-Indias I et al (2016) Normoxic recovery mimicking treatment of sleep apnea does not reverse intermittent hypoxia-induced bacterial dysbiosis and low-grade endotoxemia in mice. Sleep 39:1891–1897. https://doi.org/10.5665/sleep.6176
Ni K, Zhao L, Wu J, Chen W, HongyaYang LX (2015) Th17/Treg balance in children with obstructive sleep apnea syndrome and the relationship with allergic rhinitis. Int J Pediatr Otorhinolaryngol 79:1448–1454. https://doi.org/10.1016/j.ijporl.2015.06.026
Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177:1006–1014. https://doi.org/10.1093/aje/kws342
Shen J et al (2020) The chemopreventive effects of Huangqin-tea against AOM-induced preneoplastic colonic aberrant crypt foci in rats and omics analysis. Food Funct 11:9634–9650. https://doi.org/10.1039/d0fo01731k
Smith PM et al (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–573. https://doi.org/10.1126/science.1241165
Ye JY et al (2012) The treg/th17 imbalance in patients with obstructive sleep apnoea syndrome. Mediators Inflamm 2012:815308. https://doi.org/10.1155/2012/815308
Ye J et al (2015) CD4(+)T-lymphocyte subsets in nonobese children with obstructive sleep apnea syndrome. Pediatr Res 78:165–173. https://doi.org/10.1038/pr.2015.76
Zhang H, Hui D, Li Y, **ong G, Fu X (2019) Canmei formula reduces colitis-associated colorectal carcinogenesis in mice by modulating the composition of gut microbiota. Front Oncol 9:1149. https://doi.org/10.3389/fonc.2019.01149.eCollection2019
Zimmermann P, Messina N, Mohn WW, Finlay BB, Curtis N (2019) Association between the intestinal microbiota and allergic sensitization, eczema, and asthma: a systematic review. J Allergy Clin Immunol 143:467–485. https://doi.org/10.1016/j.jaci.2018.09.025 (Epub 2018 Dec 29 PMID: 30600099)
Acknowledgements
We thank Traci Raley, MS, ELS, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac) for editing a draft of this manuscript.
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Natural Science Foundation of Zhejiang Province (LY18H290008), Natural Science Foundation of China (81973590) and the Medical and Health Science and Technology Plan of Zhejiang Province (2019309530) provided financial support in the form of researcher funding. The sponsor had no role in the design or conduct of this research.
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FW drafted the manuscript, QYL, TYT and HYW collected the samples and analyze data, TZ contributed to perform detection and prepare tables, ZJL conceived and planned the study design. All authors read and approved the final manuscript.
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The study was conducted according to the World Medical Association Declaration of Helsinki in 1975, as revised in 1983, and was approved by the Ethic Committee of Zhejiang Hospital.
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Wang, F., Liu, Q., Wu, H. et al. The dysbiosis gut microbiota induces the alternation of metabolism and imbalance of Th17/Treg in OSA patients. Arch Microbiol 204, 217 (2022). https://doi.org/10.1007/s00203-022-02825-w
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DOI: https://doi.org/10.1007/s00203-022-02825-w