Crijevna mikrobiota kod djece s akutnim leukemijama

master's thesis

• Title (english): Intestinal microbiota in children with acute leukemias
• Author: Vid Ujaković
• Mentor: Ernest Bilić (mentor)
• Committee member: Irena Senečić-Čala (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Ernest Bilić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Akutne leukemije predstavljaju najčešću dječju malignost, a definiramo ih kao bolesti, koje karakterizira zastoj sazrijevanja i diferencijacije uz nekontrolirano dijeljenje malignih stanica limfocitnog ili mijeloidnog reda. Znajući da se i do 5% živorođene djece rađa s određenim mutacijama, koje predisponiraju za razvoj leukemije, a samo malen broj ovakve djece i oboli, počeo se razmatrati utjecaj okolišnih čimbenika u two-hit modelima razvoja leukemija. Prva teorija je bila tzv. „hipoteza odgođene infekcije“ koja se temeljila na pretpostavci da bi infekcije mogle predisponirati razvoju leukemija, uzevši u obzir sličnu dob vrhunca
incidencije, u usporedbi s drugim bolestima uz koje vežemo izlaganje stranim antigenima, poput alergija. V(D)J rekombinacija predstavlja glavnu postnatalnu genetsku modifikaciju B limfocita, no ipak pokazalo se da ona sama nije dovoljna za razvoj malignog klona, nego je potrebna i određena sklonost prema patološkom upalnom odgovoru. Znajući da je imunološki
trening B-limfocita usko povezan s crijevnom florom i da su svi čimbenici, koji utječu na smanjenu raznolikost crijevne flore djeteta (carski rez, izostanak dojenja, socijalna izolacija i antibiotici), povezani s povećanim rizikom od leukemija, smatra se da bi upravo crijevna disbioza mogla biti sekundarni čimbenik u two-hit modelima. Prilikom izrade ovog rada, prvo sam se osvrnuo na fiziološki razvoj crijevne mikrobiote djeteta i na to kako pojedini čimbenici okoliša ometaju tok razvoja crijevne flore. Nakon toga, bavio sam se crijevnom florom u trenutku postavljanja dijagnoze, a potom i interakcijom između kemoterapijskih protokola, antibiotika, razvoja GVHD-a i crijevne flore. Naposljetku, bavio sam se metodama modifikacije flore poput FMT-a, pro-, pre- i postbiotika te racionalnog korištenja antibiotika.

Abstract (english)

Acute leukemias represent the most common childhood malignancy. They are defined as
diseases characterized by arrested maturation and differentiation, accompanied by uncontrolled
proliferation of malignant cells of lymphocytic or myeloid origin. Recognizing that up to 5%
of newborns harbor mutations predisposing them to leukemia development and that only a
fraction of those develop leukemia, the influence of environment in two-hit models of leukemia
development has been contemplated. The initial theory, the "delayed infection hypothesis,"
proposed that infections predispose to leukemia development. This theory considered a shared
age peak of incidence with other diseases linked to exposure to foreign antigens, such as
allergies. While the V(D)J recombination represents a major postnatal genetic modification of
B lymphocytes, it is thought that this process alone is insufficient for the development of the
malignant clone. Rather, a predisposition to a pathological inflammatory response is required.
Understanding the association between the immune training of B lymphocytes and the gut flora,
and considering factors diminishing the diversity of gut flora (e.g., cesarean delivery, lack of
breastfeeding, social isolation and antibiotics), it has been proposed that gut dysbiosis might be
a secondary factor in two-hit models. This paper delves into the development of the gut flora
and explores how specific factors disrupt this process. Subsequently, it addresses gut dysbiosis
at the time of diagnosis, followed by an insight into the interplay between chemotherapy,
antibiotics, GVHD and gut flora. Finally, it examines methods of modifying gut flora, such as
FMT, pro-, pre- and postbiotics, as well as the rational use of antibiotics.

• Keywords: akutne leukemije; crijevna disbioza; okoliš i patogeneza leukemija; crijevna flora u liječenju leukemija; metode modifikacije crijevne flore
• Keywords (english): acute leukemias; gut dysbiosis; environment and leukemia development; gut flora in leukemia treatment; methods of gut flora modification
• Language: croatian
• URN:NBN: urn:nbn:hr:105:105589
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-07-01 17:54:26