Evaluation of Zonulin Levels, Trimethylamine-N-oxide, Indoxyl Sulphate and P-Cresol Sulphate Levels in Patients with Hashimoto's Thyroiditis

Project no. 32527 · Status: Kapanmış (Yayın bekleniyor) · 2024

Summary

<p>Hashimoto&#39;s&nbsp;thyroiditis&nbsp;(HT)&nbsp;is&nbsp;a&nbsp;common&nbsp;autoimmune&nbsp;disorder&nbsp;that&nbsp;affects&nbsp;women&nbsp;7-10&nbsp;times&nbsp;more&nbsp;frequently&nbsp;than&nbsp;men.&nbsp;It&nbsp;develops&nbsp;due&nbsp;to&nbsp;inactivation&nbsp;regions&nbsp;on&nbsp;the&nbsp;X&nbsp;chromosome,&nbsp;which&nbsp;are&nbsp;modulated&nbsp;by&nbsp;genetic&nbsp;susceptibility,&nbsp;environmental&nbsp;factors,&nbsp;and&nbsp;microbiome&nbsp;composition,&nbsp;leading&nbsp;to&nbsp;an&nbsp;imbalance&nbsp;in&nbsp;self-tolerance&nbsp;mechanisms.&nbsp;Patients&nbsp;require&nbsp;hormone&nbsp;replacement&nbsp;with&nbsp;oral&nbsp;levothyroxine,&nbsp;and&nbsp;if&nbsp;left&nbsp;untreated,&nbsp;it&nbsp;can&nbsp;have&nbsp;serious&nbsp;adverse&nbsp;effects&nbsp;on&nbsp;health&nbsp;and&nbsp;ultimately&nbsp;lead&nbsp;to&nbsp;death.&nbsp;As&nbsp;intestinal&nbsp;permeability&nbsp;is&nbsp;an&nbsp;issue&nbsp;in&nbsp;HT&nbsp;patients,&nbsp;the&nbsp;composition&nbsp;and&nbsp;abundance&nbsp;of&nbsp;the&nbsp;gut&nbsp;microbiota&nbsp;also&nbsp;show&nbsp;marked&nbsp;differences.&nbsp;This&nbsp;phenomenon&nbsp;led&nbsp;us&nbsp;to&nbsp;consider&nbsp;whether&nbsp;the&nbsp;gut&nbsp;microbiota&nbsp;could&nbsp;influence&nbsp;the&nbsp;progression&nbsp;of&nbsp;HT&nbsp;via&nbsp;permeability.&nbsp;It&nbsp;has&nbsp;been&nbsp;demonstrated&nbsp;in&nbsp;the&nbsp;literature&nbsp;that&nbsp;metabolites&nbsp;derived&nbsp;from&nbsp;the&nbsp;gut&nbsp;microbiota,&nbsp;such&nbsp;as&nbsp;uremic&nbsp;toxins&nbsp;(Trimethylamine-N-oxide&nbsp;(TMAO),&nbsp;indoxyl&nbsp;sulphate,&nbsp;and&nbsp;P-cresol&nbsp;sulphate),&nbsp;contribute&nbsp;to&nbsp;the&nbsp;progression&nbsp;of&nbsp;cardiovascular&nbsp;diseases&nbsp;associated&nbsp;with&nbsp;increased&nbsp;intestinal&nbsp;permeability.&nbsp;However,&nbsp;their&nbsp;effect&nbsp;on&nbsp;autoimmune&nbsp;diseases&nbsp;is&nbsp;unclear.&nbsp;A&nbsp;systematic&nbsp;and&nbsp;detailed&nbsp;study&nbsp;showing&nbsp;how&nbsp;HT&nbsp;patients&nbsp;are&nbsp;affected&nbsp;has&nbsp;not&nbsp;yet&nbsp;been&nbsp;conducted.&nbsp;The&nbsp;aim&nbsp;of&nbsp;the&nbsp;study&nbsp;is&nbsp;to&nbsp;examine&nbsp;zonulin&nbsp;protein&nbsp;levels&nbsp;to&nbsp;determine&nbsp;intestinal&nbsp;permeability&nbsp;in&nbsp;patients,&nbsp;to&nbsp;determine&nbsp;the&nbsp;levels&nbsp;of&nbsp;uremic&nbsp;toxins&nbsp;that&nbsp;increase&nbsp;as&nbsp;a&nbsp;result&nbsp;of&nbsp;this&nbsp;permeability,&nbsp;and&nbsp;to&nbsp;investigate&nbsp;their&nbsp;relationship&nbsp;with&nbsp;the&nbsp;disease.The&nbsp;study&nbsp;will&nbsp;include&nbsp;two&nbsp;groups:&nbsp;HT&nbsp;patients&nbsp;and&nbsp;healthy&nbsp;controls.&nbsp;Zonulin&nbsp;protein&nbsp;levels&nbsp;will&nbsp;be&nbsp;measured&nbsp;using&nbsp;the&nbsp;ELISA&nbsp;method,&nbsp;while&nbsp;trimethylamine-N-oxide&nbsp;(TMAO),&nbsp;indoxyl&nbsp;sulphate&nbsp;and&nbsp;p-cresol&nbsp;sulphate&nbsp;levels&nbsp;will&nbsp;be&nbsp;measured&nbsp;using&nbsp;the&nbsp;LC/MS-MS&nbsp;method.&nbsp;This&nbsp;study&nbsp;was&nbsp;supported&nbsp;by&nbsp;the&nbsp;<strong>Ege&nbsp;University&nbsp;Research&nbsp;and&nbsp;Research&nbsp;Unit.&nbsp;</strong></p><p></p><p>The&nbsp;unique&nbsp;aspect&nbsp;of&nbsp;the&nbsp;proposed&nbsp;project&nbsp;is&nbsp;that&nbsp;(i)&nbsp;the&nbsp;effect&nbsp;of&nbsp;increased&nbsp;levels&nbsp;of&nbsp;uremic&nbsp;toxins&nbsp;(Trimethylamine-N-oxide&nbsp;(TMAO),&nbsp;indoxyl&nbsp;sulfate&nbsp;and&nbsp;P-cresol&nbsp;sulfate)&nbsp;due&nbsp;to&nbsp;increased&nbsp;intestinal&nbsp;permeability&nbsp;in&nbsp;hypertensive&nbsp;patients&nbsp;on&nbsp;the&nbsp;disease&nbsp;is&nbsp;investigated&nbsp;for&nbsp;the&nbsp;first&nbsp;time,&nbsp;and&nbsp;(ii)&nbsp;the&nbsp;response&nbsp;in&nbsp;these&nbsp;parameters&nbsp;is&nbsp;evaluated&nbsp;by&nbsp;comparing&nbsp;it&nbsp;with&nbsp;the&nbsp;healthy&nbsp;group.</p>

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