Efekt bezlepkové diety na zbytkovou kapacitu β-buněk, imunitní funkci a střevní mikrobiom dětí s nově manifestovaným diabetem 1. typu

• Název práce v češtině: Efekt bezlepkové diety na zbytkovou kapacitu β-buněk, imunitní funkci a střevní mikrobiom dětí s nově manifestovaným diabetem 1. typu
• Název v anglickém jazyce: The effect of gluten-free diet on β-cell residual capacity, immune function and gut microbiome in children with newly diagnosed type 1. diabetes
• Klíčová slova: bezlepková dieta, diabetes 1. typu, střevní mikrobiom, střevní propustnost, zbytková kapacita β-buněk
• Klíčová slova anglicky: gluten-free diet, gut permeability, human gut microbiome, type 1 diabetes mellitus, residual β-cell capacity
• Akademický rok vypsání: 2016/2017
• Typ práce: disertační práce
• Jazyk práce: čeština
• Ústav: Pediatrická klinika (13-350)
• Vedoucí / školitel: prof. MUDr. Zdeněk Šumník, Ph.D.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 28.10.2016
• Datum zadání: 28.10.2016
• Datum potvrzení stud. oddělením: 28.10.2016
• Datum a čas obhajoby: 16.09.2021 11:00
• Datum odevzdání elektronické podoby: 23.04.2021
• Datum odevzdání tištěné podoby: 24.04.2021
• Datum proběhlé obhajoby: 16.09.2021
• Oponenti: prof. MUDr. Terezie Pelikánová, DrSc.

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Předběžná náplň práce

Patofyziologické mechanismy ovlivňující vznik diabetu 1. typu (T1D) a rychlost jeho progrese krátce po diagnóze jsou dosud neznámé. Mezi kandidátní environmentální faktory spolurozhodující o vzniku a průběhu T1D patří i lepek, jež je znám svými prozánětlivými účinky.
Cílem dizertační práce bylo posoudit vliv bezlepkové diety (GFD) na zbytkovou kapacitu β-buněk, kompenzaci T1D, střevní mikrobiom, střevní propustnost, subtypy imunitních buněk u dětí s nově diagnostikovaným T1D a vliv přenosu střevního mikrobiomu na incidenci diabetu u bezmikrobních neobézních diabetických (NOD) myší.
Na skupině 45 dětí s nově diagnostikovaným T1D (26 intervenční skupina, 19 kontrolní skupina) jsme prokázali asociaci mezi dodržováním GFD a zpomalením rychlosti ztráty zbytkové kapacity β-buněk (rozdíl v trendu poklesu C-peptidu 409 pmol/l/rok; p = 0,04) a nižším HbA1c (7,8 mmol/mol, p=0,02). Popsali jsme také taxony bakterií, jejichž četnost se po zavedení GFD změnila a prokázali změny v zastoupení některých subtypů regulačních i efektorových lymfocytů. Na střevní propustnost naopak zavedení GFD vliv nemělo. Na animálním modelu jsme rovněž prokázali, že přenesení lidského střevního mikrobiomu bezmikrobním NOD myším vede ke snížení incidence diabetu.
Podali jsme komplexní pohled na metabolické změny, které jsou u dětí s T1D asociovány s vyloučením lepku ze stravy. Svými výsledky jsme prohloubili znalosti o účincích lepku na lidský organizmus.

Předběžná náplň práce v anglickém jazyce

The pathophysiology of the onset and progression of type 1 diabetes (T1D) is not fully understood. Gluten has a proinflammatory effect on the immune system and is therefore considered as one of the factors affecting the onset and progression of T1D.
The aim of the thesis is to allow a complex insight into the role of the GFD on the residual β-cell capacity, T1D control, gut microbiome, gut permeability, subtypes of immune cells and the effect of gut microbiome transfer into germ-free non-obese diabetic (NOD) mice on the incidence of diabetes.
On the group of 45 children with T1D (26 intervention group, 19 control group) we proved the association of the GFD with slower decrease of β-cell residual capacity (the difference in the trend of C-peptide decrease 409 pmol/l/year; p = 0,04) and lower HbA1c (by 7,8 mmol/mol; p=0,02). We also described the changes in the gut bacteria that were differentially abundant after the administration of the GFD and the changes in abundance of the regulatory and effector immune cells. We showed there was no change in the gut permeability with respect to the study group. We also proved that the transfer of human gut microbiota to germ-free non-obese diabetic mice leads to the decrease in the incidence of diabetes in these mice.
Altogether, we offered a complex insight into a number of changes that are associated with the initiation of the GFD in children with T1D and thus extended the knowledge of the effects of gluten on the human body.