Vaginalni mikrobiom kot dejavnik tveganja za prezgodnji porod

doktorska disertacija

Keli Hočevar (Author), Borut Peterlin (Mentor)

Abstract

Prezgodnji porod (PP) predstavlja vodilni vzrok neonatalne obolevnosti in umrljivosti. Kljub poročani povezavi med sestavo vaginalnega mikrobioma in PP, so bile predhodne raziskave v sklepih neskladne, sistemski mehanizmi preko katerih vaginalni mikrobiom vpliva na dovzetnost za PP, pa v veliki meri nepojasnjeni. Postavili smo naslednji hipotezi: (1) z analizo vaginalnega mikrobioma bomo ugotovili razlike v sestavi med slovenskimi nosečnicami, ki so rodile pred 37. tednom nosečnosti in nosečnicami, ki so rodile ob predvidenem terminu poroda, (2) potencialne razlike v sestavi vaginalnega mikrobioma so povezane s specifičnim globalnim ekspresijskim profilom v materini periferni krvi. Z namenom oceniti vlogo vaginalnega mikrobioma pri PP smo izvedli neodvisno raziskavo 16S sekvenciranja. Pri preiskovankah s PP smo ugotovili večjo mikrobno bogatost in raznolikost, zmanjšano zastopanost rodu Lactobacillus ter povečano zastopanost rodu Gardnerella in drugih z bakterijsko vaginozo in aerobnim vaginitisom povezanih rodov. Nadalje smo izvedli globalno transkriptomsko analizo RNA-sekvenciranja materine polne periferne krvi, z namenom ugotoviti ali je tvegani vaginalni mikrobiomski profil (CST IV/CST III) povezan s sistemskimi posledicami. Zaznali smo številne biološke poti, značilno povezane s PP (CST IV/CST III) med njimi signalno pot fosfatidilinositola, JAK-STAT, Fc gama-R fagocitozo in adherentne stike ter obogatene bolezenske in funkcijske procese, vključno z vnetnim odzivom, celičnim gibanjem, aktivacijo granulocitov, fagocitozo, kemotakso, organizacijo citoskeleta in adhezijo. V opravljeni raziskavi predstavljamo nadaljnje dokaze, da je sestava vaginalnega mikrobioma povezana s PP ter morebitno povezavo tveganega profila vaginalnega mikrobioma pri PP s hkratnimi transkriptomskimi spremembami periferne krvi. Z analizo prispevamo nova znanja potencialnih dejavnikov, ki privedejo do PP.

Keywords

prezgodnji porod;vaginalni mikrobiom;sekvenciranje naslednje generacije;16S rRNA sekvenciranje;RNA-sekvenciranje;transkriptom;disertacije;

Data

Language:	Slovenian
Year of publishing:	2020
Typology:	2.08 - Doctoral Dissertation
Organization:	UL BF - Biotechnical Faculty
Publisher:	[K. Hočevar]
UDC:	577.2:579.61:618.1(043.3)
COBISS:	25046531
Views:	597
Downloads:	143
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Vaginal microbiome as risk factor for preterm birth
Secondary abstract:	Preterm birth (PTB) represents a leading cause of neonatal morbidity and mortality. Despite the reported association between vaginal microbiome and PTB, previous research has been inconsistent in its conclusions, and the systemic mechanisms through which the vaginal microbiome influences susceptibility to PTB remain unexplained. We set the following hypotheses: (1) analysis of the vaginal microbiome will reveal differences in the composition between Slovenian pregnant women who delivered before completed 37th week of gestation and pregnant women who delivered at term, (2) potential differences in the composition of the vaginal microbiome are associated with a specific global expression profile in maternal peripheral blood. To re-evaluate the role of the vaginal microbiome in PTB, we conducted an independent 16S sequencing study. In PTB women, we report higher microbial richness and diversity, decreased abundance of genus Lactobacillus, increased abundance of Gardnerella, and other bacterial vaginosis and aerobic vaginitis-related genera. We performed a global transcriptomic analysis of maternal whole peripheral blood to determine whether a high-risk vaginal microbiome profile (CST IV/CST III) is associated with systemic consequences. We identified several biological pathways associated with PTB (CST IV/CST III), including phosphatidylinositol signaling pathway, JAK-STAT, Fc gamma-R phagocytosis, and adherent junctions, as well as enriched diseases and functions, including inflammatory response, cell movement, granulocyte activation, phagocytosis, chemotaxis, cytoskeletal organization, and adhesion. The present study represents further evidence that the vaginal microbiome composition is associated with PTB and the possible association of risk vaginal microbiome profile with concomitant transcriptomic changes in peripheral blood. We contribute new knowledge about the potential factors leading to PTB.
Secondary keywords:	preterm birth;vaginal microbiome;next-generation sequencing;16S rRNA sequencing;RNA-sequencing;transcriptome;
Type (COBISS):	Doctoral dissertation
Study programme:	0
Thesis comment:	Univ. v Ljubljani, Biotehniška fak.
Pages:	X, 95 f.
ID:	11950253