The Effect On The Level Of Plasma Gastrointestinal Hormones And Bile Acids Of The Patients With Functional Constipation By Transcutaneous Neuromodulation Therapy

Backgroud and objective:As a common functional gastrointestinal disease,functional constipation(FC)is mainly characterized by low defecation frequency,defecation difficulty,and defecation.Recently,Transcutaneous Neuromodulation(TN)has gained much attention due to its electroacupuncture and acupuncture-like effect,which is non-invasive and more operative.In preliminary study,patients benefited a lot from TN on Zusanli and Posterior tibial nerve.As the imbalance of gastrointestinal hormone in FC patients becomes more and more attractive,emerging evidence have confirmed that electroacupuncture and acupuncture may play an vital role in regulation the disorder.Serotonin(5-HT),one of the essential gut hormone secreted from entero-chromaffin cells can be activated by bile acids which is suggested in newly researches.Meanwhile,the abnormal metabolism of bile acids was found in patients with FC,indicating its role in modulation of gut function and hormone secretion to influence gut transmission.Therefore,the experiment aims to observe the impacts of TN treatment on the level of plasma gastrointestinal hormones and bile acids and to further explore its mechanism.Methods:According to the adjusted inclusion and exclusion standards.The FC patients and healthy volunteers were recruited,dividing into treatment group and healthy control group.Because the previous study has established sham-TN as a control,and the effectiveness of TN treatment was proved.This study aimed to explore the TN treatment mechanism for the purpose,so we did not set up sham-TN group.Following 1 week's non-interventional clinical observation.the TN treatment was used for Zusanli and Posterior Tibial Nerve twice a day(Stimulus parameters:Train On-time of 2sec and offtime of 3sec,pulse width of 0.5ms,Pulse frequency of 25Hz,and amplitude of 2-10mA)for 4 weeks.And then the patients were followed for 4 weeks.Treatment responses were evaluated by Patient Assessment of Constipation Symptom(PAC-SY),Patient Assessment of Constipation Quality of Life(PAC-QOL),Bristol score(BSS),Self-rating Anxiety scale(SAS).and Self-rating Depression Scale(SDS).Blood samples were collected before and after 4 weeks' treatment.Plasma levels of 5-HT.Motilin(MTL),Somatostatin(SS)and Vasoactive intestinal peptide(VIP)were measured by enzyme linked immunosorbent assay.liquid chromatography tandem mass spectrometry was used for determining the level of 12 kinds of bile acids(Tauroursodeoxycholate TUDCA.Taurocholic acid hydrate TCA,Taurochenodeoxycholate TCDCA,Taurodeoxycholate hydrate TDCA,Chenodeoxycholate CDCA.Ursodeoxycholic acid UDCA,Cholic acid CA,Lithocholic acid LCA,Taurolithocholate TLCA,Glycochenodeoxycholic acid GCDCA,Glycocholic acid hydrate GCA.Glycodeoxycholic acid GDCA).Results:20 patients were enrolled and 17 of them finished the treatment,while 20 healthy people were enrolled as controls.1.The frequency of spontaneous defecation was improved,PAC-SYM and PAC-QOL scores decreased after treatment at the 3rd.4th and 8th week(P<0.05).SAS and SDS scores decreased after treatment at the 4th and 8th week(P<0.05).The BSS after treatment returned to type 3 and type 4 at 4th week.2.Before treatment,the plasma level of 5-HT and MTL of the FC patients were lower than healthy controls,while the plasma level of SS were higher than healty controls(P<0.05).After treament.the FC patient's plasma level of 5-HT and MTL were higher than before,while the plasma level of SS were lower(P<0.05).After treatment,the plasma level of 5-HT and SS was no significant difference compared with the healthy controls.the plasma level of MTL were lower than healthy controls(P>0.05).There was no significant difference in the plasma level of VIP between groups(P>0.05).3.Compared with the healthy control group,the plasma level of TDCA,TCA,TLCA in FC group increased significantly.After treament the plasma level of TDCA?TCA?TLCA were lower than before(P<0.05).There was no significant difference in the plasma level of TUDCA,TCDCA,UDCA,CDCA,GCA,GCDCA,GDCA,CA between groups(P>0.05).LCA before and after treatment were lower than the detection limit.4.There was no significant correlation between gastrointestinal hormones(5-HT,MTL,SS)and subtype bile acids(TDCA,TCA,TLCA)(P>0.05).Conclusions:1.TN treatment can relief the symptoms of FC,improve the life quality and symptom of anxiety and depression with high safety.It was effective after 4 week's follow-up.2.FC patients have gastrointestinal hormones disorders.The plasma level of MTL and 5-HT may be increased by the TN treatment,while the plasma level of SS may be decreased.3.FC patients have bile acid metabolism disorders.TN may regulate the bile acid metabolism of FC patients.4.There was no significant correlation between gastrointestinal hormones(5-HT,MTL,SS)and subtype bile acids(TDCA,TCA,TLCA)of FC patients.