Characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome

CHEN Yue; LU Yan-Bo; WU Jun-Hua; QIU Hai-Yan

doi:10.7499/j.issn.1008-8830.2309129

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Chinese Journal of Contemporary Pediatrics ›› 2024, Vol. 26 ›› Issue (6) : 575-583. DOI: 10.7499/j.issn.1008-8830.2309129

CLINICAL RESEARCH

Characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome

CHEN Yue, LU Yan-Bo, WU Jun-Hua, QIU Hai-Yan

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Abstract

Objective To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites. Results A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (P<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and L-isoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, N-acetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (P<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (P<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism. Conclusions Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS.

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Obstructive sleep apnea-hypopnea syndrome / Intestinal metabolite / Biomarker / Metabolic function / Child

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CHEN Yue, LU Yan-Bo, WU Jun-Hua, QIU Hai-Yan. Characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(6): 575-583 https://doi.org/10.7499/j.issn.1008-8830.2309129

References

1 Bitners AC, Arens R. Evaluation and management of children with obstructive sleep apnea syndrome[J]. Lung, 2020, 198(2): 257-270. PMID: 32166426. PMCID: PMC7171982. DOI: 10.1007/s00408-020-00342-5.
2 Lo Bue A, Salvaggio A, Insalaco G. Obstructive sleep apnea in developmental age. A narrative review[J]. Eur J Pediatr, 2020, 179(3): 357-365. PMID: 31940071. DOI: 10.1007/s00431-019-03557-8.
3 Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of childhood obstructive sleep apnea syndrome[J]. Pediatrics, 2012, 130(3): 576-584. PMID: 22926173. DOI: 10.1542/peds.2012-1671.
4 Menzies B, Teng A, Burns M, et al. Neurocognitive outcomes of children with sleep disordered breathing: a systematic review with meta-analysis[J]. Sleep Med Rev, 2022, 63: 101629. PMID: 35439720. DOI: 10.1016/j.smrv.2022.101629.
5 Gulotta G, Iannella G, Vicini C, et al. Risk factors for obstructive sleep apnea syndrome in children: state of the art[J]. Int J Environ Res Public Health, 2019, 16(18): 3235. PMID: 31487798. PMCID: PMC6765844. DOI: 10.3390/ijerph16183235.
6 Nowak N, Engler A, Thiel S, et al. Validation of breath biomarkers for obstructive sleep apnea[J]. Sleep Med, 2021, 85: 75-86. PMID: 34280868. DOI: 10.1016/j.sleep.2021.06.040.
7 Yoon DW, Shin HW. Sleep tests in the non-contact era of the COVID-19 pandemic: home sleep tests versus in-laboratory polysomnography[J]. Clin Exp Otorhinolaryngol, 2020, 13(4): 318-319. PMID: 33176398. PMCID: PMC7669320. DOI: 10.21053/ceo.2020.01599.
8 Zhang X, Wang S, Xu H, et al. Metabolomics and microbiome profiling as biomarkers in obstructive sleep apnoea: a comprehensive review[J]. Eur Respir Rev, 2021, 30(160): 200220. PMID: 33980666. PMCID: PMC9489097. DOI: 10.1183/16000617.0220-2020.
9 Bujak R, Struck-Lewicka W, Markuszewski MJ, et al. Metabolomics for laboratory diagnostics[J]. J Pharm Biomed Anal, 2015, 113: 108-120. PMID: 25577715. DOI: 10.1016/j.jpba.2014.12.017.
10 Xue J, Allaband C, Zhou D, et al. Influence of intermittent hypoxia/hypercapnia on atherosclerosis, gut microbiome, and metabolome[J]. Front Physiol, 2021, 12: 663950. PMID: 33897472. PMCID: PMC8060652. DOI: 10.3389/fphys.2021.663950.
11 Allaband C, Lingaraju A, Martino C, et al. Intermittent hypoxia and hypercapnia alter diurnal rhythms of luminal gut microbiome and metabolome[J]. mSystems, 2021, 6(3): e0011621. PMID: 34184915. PMCID: PMC8269208. DOI: 10.1128/mSystems.00116-21.
12 Wu J, Lu Y, Cai X, et al. Gut microbiota dysbiosis in 4- to 6-year-old children with obstructive sleep apnea-hypopnea syndrome[J]. Pediatr Pulmonol, 2022, 57(9): 2012-2022. PMID: 35580999. DOI: 10.1002/ppul.25967.
13 中国儿童OSA诊断与治疗指南制订工作组, 中华医学会耳鼻咽喉头颈外科学分会小儿学组, 中华医学会儿科学分会呼吸学组, 等. 中国儿童阻塞性睡眠呼吸暂停诊断与治疗指南（2020）[J]. 中国循证医学杂志, 2020, 20(8): 883-900. DOI: 10.7507/1672-2531.202005147.
14 Ko CY, Liu QQ, Su HZ, et al. Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities[J]. Clin Sci (Lond), 2019, 133(7): 905-917. PMID: 30957778. PMCID: PMC6465302. DOI: 10.1042/CS20180891.
15 Liu G, Li J, Li Y, et al. Gut microbiota-derived metabolites and risk of coronary artery disease: a prospective study among US men and women[J]. Am J Clin Nutr, 2021, 114(1): 238-247. PMID: 33829245. PMCID: PMC8277432. DOI: 10.1093/ajcn/nqab053.
16 Yu L, Xu Q, Wang P, et al. Secoisolariciresinol diglucoside-derived metabolite, enterolactone, attenuates atopic dermatitis by suppressing Th2 immune response[J]. Int Immunopharmacol, 2022, 111: 109039. PMID: 35914449. DOI: 10.1016/j.intimp.2022.109039.
17 Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, et al. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes[J]. Front Genet, 2015, 6: 148. PMID: 25941533. PMCID: PMC4403557. DOI: 10.3389/fgene.2015.00148.
18 Lau SK, Lam CW, Curreem SO, et al. Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway[J]. Cell Biosci, 2015, 5: 26. PMID: 26097677. PMCID: PMC4475313. DOI: 10.1186/s13578-015-0018-x.
19 Chen Z, Han S, Zhou D, et al. Effects of oral exposure to titanium dioxide nanoparticles on gut microbiota and gut-associated metabolism in vivo[J]. Nanoscale, 2019, 11(46): 22398-22412. PMID: 31738363.DOI: 10.1039/c9nr07580a.
20 Jira W, Spiteller G, Carson W, et al. Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients[J]. Chem Phys Lipids, 1998, 91(1): 1-11. PMID: 9488997. DOI: 10.1016/s0009-3084(97)00095-9.
21 Corteselli EM, Gibbs-Flournoy E, Simmons SO, et al. Long chain lipid hydroperoxides increase the glutathione redox potential through glutathione peroxidase 4[J]. Biochim Biophys Acta Gen Subj, 2019, 1863(5): 950-959. PMID: 30844486. PMCID: PMC6823641. DOI: 10.1016/j.bbagen.2019.03.002.
22 Leroux M, Lemery T, Boulet N, et al. Effects of the amino acid derivatives, β-hydroxy-β-methylbutyrate, taurine, and N-methyltyramine, on triacylglycerol breakdown in fat cells[J]. J Physiol Biochem, 2019, 75(3): 263-273. PMID: 30919256. DOI: 10.1007/s13105-019-00677-5.
23 Choi HS, Kim SL, Kim JH, et al. Plant volatile, phenylacetaldehyde targets breast cancer stem cell by induction of ROS and regulation of Stat3 signal[J]. Antioxidants (Basel), 2020, 9(11): 1119. PMID: 33202749. PMCID: PMC7697623. DOI: 10.3390/antiox9111119.
24 Swietlik EM, Ghataorhe P, Zalewska KI, et al. Plasma metabolomics exhibit response to therapy in chronic thromboembolic pulmonary hypertension[J]. Eur Respir J, 2021, 57(4): 2003201. PMID: 33060150. PMCID: PMC8012591. DOI: 10.1183/13993003.03201-2020.
25 Naudí A, Caro P, Jové M, et al. Methionine restriction decreases endogenous oxidative molecular damage and increases mitochondrial biogenesis and uncoupling protein 4 in rat brain[J]. Rejuvenation Res, 2007, 10(4): 473-484. PMID: 17716000. DOI: 10.1089/rej.2007.0538.
26 Ren B, Wang L, Mulati A, et al. Methionine restriction improves gut barrier function by reshaping diurnal rhythms of Inflammation-Related microbes in aged mice[J]. Front Nutr, 2021, 8: 746592. PMID: 35004799. PMCID: PMC8733897. DOI: 10.3389/fnut.2021.746592.
27 Xu Z, Wu Y, Tai J, et al. Risk factors of obstructive sleep apnea syndrome in children[J]. J Otolaryngol Head Neck Surg, 2020, 49(1): 11. PMID: 32131901. PMCID: PMC7057627. DOI: 10.1186/s40463-020-0404-1.
28 Chuang HH, Hsu JF, Chuang LP, et al. Different associations between tonsil microbiome, chronic tonsillitis, and intermittent hypoxemia among obstructive sleep apnea children of different weight status: a pilot case-control study[J]. J Pers Med, 2021, 11(6): 486. PMID: 34071547. PMCID: PMC8227284. DOI: 10.3390/jpm11060486.
29 Sookoian S, Pirola CJ. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis[J]. Obes Surg, 2013, 23(11): 1815-1825. PMID: 23740153. DOI: 10.1007/s11695-013-0981-4.
30 Byrne TJ, Parish JM, Somers V, et al. Evidence for liver injury in the setting of obstructive sleep apnea[J]. Ann Hepatol, 2012, 11(2): 228-231. PMID: 22345340.
31 Chen LD, Huang ZW, Huang YZ, et al. Untargeted metabolomic profiling of liver in a chronic intermittent hypoxia mouse model[J]. Front Physiol, 2021, 12: 701035. PMID: 34305653. PMCID: PMC8298499. DOI: 10.3389/fphys.2021.701035.
32 Wlodarska M, Luo C, Kolde R, et al. Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation[J]. Cell Host Microbe, 2017, 22(1): 25-37.e6. PMID: 28704649. PMCID: PMC5672633. DOI: 10.1016/j.chom.2017.06.007.
33 Wang F, Zou J, Xu H, et al. Effects of chronic intermittent hypoxia and chronic sleep fragmentation on gut microbiome, serum metabolome, liver and adipose tissue morphology[J]. Front Endocrinol (Lausanne), 2022, 13: 820939. PMID: 35178032. PMCID: PMC8846366. DOI: 10.3389/fendo.2022.820939.
34 Zeng Z, Jin T, Ni J, et al. Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study[J]. Semin Arthritis Rheum, 2022, 57: 152095. PMID: 36126568. DOI: 10.1016/j.semarthrit.2022.152095.
35 Zhang X, Coker OO, Chu ES, et al. Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites[J]. Gut, 2021, 70(4): 761-774. PMID: 32694178. PMCID: PMC7948195. DOI: 10.1136/gutjnl-2019-319664.
36 Meslier V, Laiola M, Roager HM, et al. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake[J]. Gut, 2020, 69(7): 1258-1268. PMID: 32075887. PMCID: PMC7306983. DOI: 10.1136/gutjnl-2019-320438.
37 Dong Y, Wang P, Lin J, et al. Characterization of fecal metabolome changes in patients with obstructive sleep apnea[J]. J Clin Sleep Med, 2022, 18(2): 575-586. PMID: 34534066. PMCID: PMC8804979. DOI: 10.5664/jcsm.9668.
38 Xu H, Li X, Zheng X, et al. Pediatric obstructive sleep apnea is associated with changes in the oral microbiome and urinary metabolomics profile: a pilot study[J]. J Clin Sleep Med, 2018, 14(9): 1559-1567. PMID: 30176961. PMCID: PMC6134247. DOI: 10.5664/jcsm.7336.
39 Zhang Y, Luo H, Niu Y, et al. Chronic intermittent hypoxia induces gut microbial dysbiosis and infers metabolic dysfunction in mice[J]. Sleep Med, 2022, 91: 84-92. PMID: 35286865. DOI: 10.1016/j.sleep.2022.02.003.