Mehanizmi delovanja probiotičnih in protektivnih bakterij PCS 20, PCS 26 ter LGG v preprečevanju metaboličnega sindroma

Gorenjak, Mario

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Title:	Mehanizmi delovanja probiotičnih in protektivnih bakterij PCS 20, PCS 26 ter LGG v preprečevanju metaboličnega sindroma
Authors:	ID Gorenjak, Mario (Author) ID Skok, Pavel (Mentor) More about this mentor... ID Langerholc, Tomaž (Comentor)
Files:	DR_Gorenjak_Mario_2014.pdf (26,41 MB) MD5: D247D0AA0C54AA4EF4582589B64EB4C7
Language:	Slovenian
Work type:	Dissertation
Organization:	MF - Faculty of Medicine
Abstract:	Metabolični sindrom, znan tudi kot »sindrom X« ali »sindrom inzulinske rezistence«, narašča po vsem svetu, vključno z državami v razvoju. Presnovni sindrom je sestav klinično izraženih znakov, kot so centralna debelost, visok krvni tlak, povišana raven plazemske glukoze na tešče ali diagnosticirana sladkorna bolezen, nizek HDL in povišani serumski trigliceridi. Vse te sestavine skupaj ali posamezno vplivajo na razvoj srčno-žilnih bolezni, ki so vodilni vzrok smrti v sodobnem svetu. Izsledki preteklih raziskav so pokazali, da lahko probiotične/protektivne bakterije vplivajo na izboljšanje zdravja s pozitivnimi učinki na bolezni, ki so sestavine presnovnega sindroma, in sicer sladkorna bolezen, povišan krvni tlak, dislipidemija in nizkostopenjsko vnetje. Cilji doktorske disertacije so bili, ugotoviti, kateri izmed probiotičnih/protektivnih sevov Lactobacillus plantarum PCS 20, Lactobacillus plantarum PCS 26 in Lactobacillus rhamnosus GG deluje pozitivno v kaskadi molekularnih reakcij na ravni tankega črevesja, remodeliranja monocitov/makrofagov in adipocitov v humanem celičnem modelu nekarcinogenega izvora, ter podati znanstveno razlago mehanizmov možnega pozitivnega večnivojskega delovanja izbranih probiotičnih/protektivnih sevov pri bolnikih s presnovnim sindromom. V ta namen smo raziskavo razdelili na dva dela. Prvi del je zajemal predklinično in vitro laboratorijsko študijo, ki je ena izmed prvih v svetovnem merilu, ki je preučevala mehanizme delovanja probiotičnih/protektivnih bakterij v preprečevanju presnovnega sindroma z uporabo funkcionalnih celičnih modelov nekarcinogenega izvora, natančneje z uporabo celičnih linij humanega črevesnega epitelija, humanih monocitov/makrofagov in humanih visceralnih preadipocitov. Z in vitro laboratorijsko študijo smo dokazali, da probiotični/protektivni sev Lactobacillus plantarum PCS 26 izraža pozitivne učinke, ki bi v gostitelju s presnovnim sindromom lahko pripomogli k lajšanju posameznih sestavin sindroma, in hkrati uvedli tudi nov pristop k raziskovanju biosubstanc z uporabo funkcionalnih celičnih modelov humanega nekarcinogenega izvora. Drugi del raziskave je zajemal prospektivno, dvojno slepo in s placebom kontrolirano in vivo pilotno klinično študijo, v katero je bilo zajetih 16 prostovoljcev s presnovnim sindromom. Rezultati raziskav so pokazali, da probiotični protektivni sev Lactobacillus plantarum PCS 26 pozitivno vpliva na zmanjšanje obsega pasu, na znižanje koncentracije serumskega holesterola in na vzdrževanje ravni adiponektina v serumu. Ti vplivi skupaj pa lahko pripomorejo k lajšanju presnovnega sindroma predvsem z vidika klinične manifestacije in tveganj v povezavi s srčno-žilnimi boleznimi. Izvedene raziskave predstavljajo temeljno izhodišče za načrtovanje in izvedbo dolgoročne klinične študije v velikem obsegu, ki bi nam omogočila podrobnejši vpogled v mehanizme delovanja probiotičnih/protektivnih bakterij v preprečevanju ali lajšanju presnovnega sindroma.
Keywords:	presnovni sindrom, debelost, inzulinska rezistenca, dislipidemija, probiotične bakterije, funkcionalni celični modeli.
Place of publishing:	Maribor
Year of publishing:	2014
PID:	20.500.12556/DKUM-46643
COBISS.SI-ID:	5141055
NUK URN:	URN:SI:UM:DK:YQ1DVWVZ
Publication date in DKUM:	05.11.2014
Views:	3005
Downloads:	517
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Categories:	MF
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Secondary language

Language:	English
Title:	Mechanisms of action of probiotic and protective bacteria PCS 20, PCS 26, and LGG in prevention of the metabolic syndrome
Abstract:	The metabolic syndrome, also known as »syndrome X« or »insulin resistance syndrome«, is increasing worldwide, including developing countries. The metabolic syndrome is composed of clinical expressed symptoms as central obesity, high blood pressure, raised fasting plasma glucose or diagnosed diabetes, low HDL, and raised serum triglycerides. All those components together or independently contribute to the development of cardiovascular diseases, which are the leading cause of death in the modern world. The results from previous studies have shown that probiotic/protective bacteria have an influence on health improvement, and can exert positive effects on diseases as diabetes, high blood pressure, dyslipidemia and low-grade inflammation, which are all components of the metabolic syndrome. The objectives of this doctoral dissertation were to investigate which of probiotic/protective strains Lactobacillus plantarum PCS 20, Lactobacillus plantarum PCS 26 in Lactobacillus rhamnosus GG exert positive effects in the cascade of molecular reactions at the level of small intestines, at remodeling of monocytes/macrophages and adipocytes in human cell model of non-cancerous origin, and to provide scientific explanation of mechanisms of possible multi-leveled activity of selected probiotic/protective strains in patients with metabolic syndrome. For this purpose, we divided this research into two parts. The first part consisted of pre-clinical in-vitro laboratory study, which is one of the first in the world. It examined the mechanisms of actions of probiotic/protective cultures with the use of functional cell models of non-cancerous origin, more specifically, with the use of cell lines of human intestinal epithelium, human monocytes/macrophages and human visceral preadipocytes. In in-vitro laboratory study, we demonstrated that probiotic/protective strain Lactobacillus plantarum PCS 26 exerts positive effects, which could help to relieve the particular components of the syndrome in the host with metabolic syndrome, and also introduced a new approach to investigation of biosubstances with the use of functional cell models of human, non-cancerous origin. The second part of the research consisted of prospective, double-blind and placebo-controlled in-vivo pilot clinical study, which included 16 volunteers with the metabolic syndrome. Results have shown that probiotic/protective strain Lactobacillus plantarum PCS 26 exerts positive effects on reduction of waist circumference, on lowering of serum cholesterol concentration, and on maintenance of serum adiponektin levels. Those effects together can contribute to the alleviation of the metabolic syndrome, especially in terms of clinical manifestation and risks in relation to cardiovascular diseases. The conducted research represents a fundamental starting point for the planning and realization of long-term, large-scale clinical study, which would allow us a more detailed insight into the mechanisms of action of probiotic/protective cultures in the prevention or alleviation of the metabolic syndrome.
Keywords:	metabolic syndrome, obesity, insulin resistance, dyslipidemia, probiotic bacteria, functional cell models.

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