The Effect Of Tryptophan Metabolites On The Relationship Of Antibiotics Internal Exposure And Sleep Duration In The Elderly

Objective:To describe the level of urinary antibiotics,the level of serum tryptophan metabolites and sleep status of the elderly in Lu’an City,Anhui Province.Meanwhile,to investigate the relationship of urinary antibiotics concentration and sleep duration,the relationship of serum tryptophan metabolites level and sleep duration and the moderation effect of tryptophan metabolites on the relationship of antibiotics internal exposure and sleep duration.Methods:During June to September 2016,the cohort selected 1080 elderly people to conduct the questionnaire to obtain the basic information of the population including sleep status by stratified cluster sampling;By liquid chromatography-tandem mass spectrometry,the antibiotics concentration and serum tryptophan metabolites level of 986elderly were detected;the disparity of basic characteristic and detection frequency of the elderly with different sleep duration were described by variance analysis and Chi-square test,respectively;The distribution disparity of antibiotics concentration and tryptophan metabolites level of the elderly with different sleep duration were described by Mann-Whitney test;The linear correlation relationship among antibiotics concentration,tryptophan metabolites level and sleep duration were investigated by linear regression model;Binary logistic regression model was fitted to characterize the association of antibiotics concentration,tryptophan metabolites level and the risk of abnormal sleep duration.The tendency of the correlation of tryptophan metabolites level and abnormal sleep duration risk were characterized by the restricted cubic splines;Moderation effect model was applied to evaluate the moderation effect of tryptophan metabolites on the relationship between antibiotics internal exposure and sleep duration.Results:The number of the population with antibiotics concentration ranged 10-20μg/g in the abnormal nightly sleep duration was largest（17.8%）,while the number of the population with antibiotics concentration ranged 5-10μg/g in the normal nightly sleep duration was largest（17.0%）.The linear regression of antibiotics concentration and nightly sleep duration indicated that Tetracycline（TC）or Chloramphenicols（CAPs）had a negative correlation with nightly sleep duration（β:-0.08,95%CI:-0.51～-0.01）,（β:-0.11,95%CI:-0.96～-0.19）;The logistic regression revealed that the elderly with low levels of Oxytetracycline（OTC）had a lower risk of abnormal nightly sleep duration,compared to the reference（OR:0.49,95%CI:0.29～0.85）;The elderly with high levels of Azithromycin（AZI）had a higher risk of abnormal nightly sleep duration,compared to the reference（OR:1.95,95%CI:1.04～3.68）;The elderly with low levels of Doxycycline（DC）had a lower risk of abnormal total sleep duration,compared to the reference（OR:0.48,95%CI:0.24～0.96）.The level of Kynurenine/Tryptophan（KYN/TRP）or Kynurenic acid/Kynurenine（KA/KYN）was different between varied nightly sleep duration groups statistically（P=0.048,P=0.004）.The linear regression of antibiotics concentration and tryptophan metabolites concentration revealed that OTC,TC,Ofloxacin（OFX）or Ciprofloxacin（CFX）had a positive correlation with TRP（β:0.017,95%CI:0.006～0.027）,（β:0.026,95%CI:0.013～0.039）,（β:0.010,95%CI:0.002～0.018）,（β:0.009,95%CI:0.000～0.017）;DC had a negative correlation with KA（β:-0.023,95%CI:-0.043～-0.003）;OTC or TC had a positive correlation with Xanthurenic acid（XA）（β:0.014,95%CI:0.006～0.028）,（β:0.017,95%CI:0.013～0.042）;AZI had a negative correlation with 5-Hydroxytryptamine（5-HT）（β:-0.062,95%CI:-0.115～-0.008）;DC,CFX or Norfloxacin（NFX）had a positive correlation with Tryptamine（TA）（β:0.006,95%CI:0.010～0.109）,（β:0.047,95%CI:0.018～0.076）,（β:0.031,95%CI:0.005～0.057）;DC had a negative correlation with Indole-3-acetic acid（IAA）（β:-0.033,95%CI:-0.066～-0.001）;OTC、DC had a negative correlation with Indole-3-propionic acid（IPA）（β:-0.084,95%CI:-0.142～-0.025）,（β:-0.106,95%CI:-0.185～-0.027）;Florfenicol（FF）had a positive correlation with IPA（β:0.065,95%CI:0.016～0.114）.The linear regression of tryptophan metabolites concentration and nightly sleep duration revealed that KYN had a positive correlation with nightly sleep duration（β:0.69,95%CI:0.01～1.38）.The logistic regression of tryptophan metabolites and the risk of abnormal nightly sleep duration indicated that the elderly with KYN or 5-HT ranged P₃₃-P₆₆ concentration had a lower risk of abnormal nightly sleep duration（OR:0.54,95%CI:0.37～0.80）,（OR:0.65,95%CI:0.43～0.96）,compared to the reference;The elderly with KYN ranged>P₆₆concentration had a lower risk of abnormal nightly sleep duration（OR:0.54,95%CI:0.36～0.80）,the disparity existed between men and women;The elderly with IPA ranged>P₆₆ concentration had a lower risk of abnormal total sleep duration（OR:0.64,95%CI:0.44～0.93）;The elderly with XA ranged>P₆₆ concentration had a lower risk of abnormal total sleep duration（OR:1.52,95%CI:1.02～2.25）.Restricted cubic splines revealed that a non-linear correlation existed between 5-HT,KA/KYN and abnormal nightly sleep duration（P=0.009,P=0.045）respectively.5-HT had a moderation effect between the relationship of OTC and nightly sleep duration（β=0.07,t=2.23,P=0.026）;5-HT,TA had a moderation effect between the relationship of TC and nightly sleep duration（β=0.12,t=2.46,P=0.014）,（β=-0.12,t=-2.00,P=0.046）;XA had a moderation effect between the relationship of Enrofloxacin（EFX）and nightly sleep duration（β=-0.17,t=-2.50,P=0.013）;KA had a moderation effect between the relationship of AZI and total sleep duration（β=0.23,t=2.35,P=0.019）;TA had a moderation effect between the relationship of TC and total sleep duration（β=-0.15,t=-2.08,P=0.038）;TRP,TA had a moderation effect between the relationship of DC and total sleep duration（β=0.15,t=1.97,P=0.049）,（β=0.17,t=2.09,P=0.037）;Conclusion:（1）The elderly with low levels of OTC or DC had a lower risk of abnormal sleep duration,while the elderly with high levels of AZI had a higher risk of abnormal sleep duration（2）There is a linear correlation among antibiotics concentration and the level of TRP,XA,KA,5-HT,IAA or IPA.（3）KYN,5-HT or KYN/TRP had a lower risk of abnormal sleep duration.KA/KYN or XA/KYN had a higher risk of abnormal sleep duration.（4）TRP,5-HT,TA,XA or KA/KYN had a moderation effect on the relationship between antibiotics exposure and sleep duration.