Aknu steatozes riska faktoru un fēču mikrobioma saistības izvērtējums pacientiem ar neinsulīnatkarīgu cukura diabētu

Abstract

Aktualitāte.Aptuveni divām trešdaļām 2TDM pacientu ir NTAS. 2TDM ir riska faktors tam, lai NTAS attīstītos par steatohepatītu, aknu fibrozi un cirozi. NTAS progresija ir biežāka pacientiem ar augstāku ĶMI, VA un TG līmeni. Ir noteikts, ka šajā pacientu grupā daži zarnu mikrobiāta metagenomiskie modeļi var kalpot par aknu iekaisuma radītājiem. Uzlabotas mikrobiomu analīzes metodes un dziļāka izpratne par sakarībām starp disbiozi un tās ietekmi uz kuņģa-aknu asi var uzlabot NTAS diagnostiku un ārstēšanu. Mērķi.Analizēt sakarību starp fēču mikrobiomu un ALAT līmeni, triglicerīdu līmeni, ĶMI un VA 2TDM pacientiem. Materiāli un metodes.Dati tika iegūti retrospektīvi par 2TDM pacientiem, kuriem tikko uzstādīta diagnoze un kuri iekļauti OPTIMED pētījumā no 2015. gada jūnija līdz 2016. gada maijam. Izslēgšanas kritēriji: antibiotiku, antidiabētisku medikamentu, probiotiķu, imūnsupresoru/kortikosteroīdu lietošana pēdējo divu mēnešu laikā, alerģija pret noteiktajiem antidibētiskajiem medikamentiem, hroniskas kuņģa-zarnu, autoimūnas un onkoloģiskas slimības, nieru vai aknu darbības traucējumi, alkoholisms un diareja iepriekšējās nedēļas laikā. Tika veikti antropomeriskie mērījumi, iegūti asins paraugi (triglicerīdu, holesterola un ALAT līmeņu noteikšanai) un fēču paraugi mikrobiāta analīzei. Lai noteiktu baktēriju tipus un ģintis, tika veikta 16S rRNA gēnu analīze. Rezultāti.Pētījumā tika iekļauti 11 pacienti, septiņiem no tiem bija paaugstināts ALAT līmenis (≥29 IU/l ♂, ≥22 IU/l♀).Starp grupām netika atrastas zīmīgas atšķirības (antropometriskie mērījumi, holesterols), kā arī grupu mikrobiāta sastāvā nebija zīmīgu atšķirību tipa līmenī.Ģints līmenī paaugstināta ALAT grupā tika noteikts zīmīgi augstāks Coriobacteriaceae_unclassified (p=0.02) un Lachnospiraceae_UCG-010 (p=0.04) līmenis,bet Coprococcus_1 (p=0.01) un Romboutsia (p=0.01) lielāks apjoms bija grupā ar normālu ALAT līmeni.Tipa līmenī ŠDI negatīvi korelēja ar TG (r=-0.800, p=0.003).Bacteroidetes negatīvi korelēja ar VA (r=0.706,p=0.015) un TG (r=0.755,p=0.01).Firmicutes: ar VA (r=0.706,p=0.015) un TG (r=0.755,p=0.01). Ģints līmenī ŠDI negatīvi korelēja ar ĶMI (r=-0.691, p=0.019), bet nekorelēja ar ALAT, VA un TG. TG: ar Ruminococcaceae_UCG-002 (r=-0.618,p=0.04) un Subdoligranulum (r=-0.86,p=0.001). ĶMI: ar Ruminococcaceae_UCG-004 (r=-0.67,p=0.02),Butyricimonas (r=-0.73,p=0.01),Flavonifractor (r=0.62,p=0.04),Holdemania (r= 0.715,p=0.013). VA: ar Holdemania (r=-0.779,p=0.005),Bacteroides (r= 0.688,p=0.019),Parvibacter (r=-0.646,p=0.032), Lactobacillus (r=0.623,p=0.04) un Ruminococcus_2 (r=-0.679, p=0.022). ALAT: ar [Erysipelotrichaceae] (r=0.61,p=0.04),Romboutsia (r=0.7,p=0.01),Blautia (r=-0.75,p=0.01) un [Eubacterium]_hallii_group (r=-0.62,p=0.04).

Background.Approximately two thirds of T2DM patients have NAFLD. T2DM is a risk factor for the development and progression of NAFLD to steatohepatitis, liver fibrosis and cirrhosis. Progression of NAFLD is more prevalent in patients with higher BMI, WC and TG levels. It has been postulated that certain metagenomic patterns of the gut microbiota may serve as inflammation inducer in liver in this patient population. Improved methods of analysis of the microbiomes and greater understanding of the interactions between dysbiosis and their effects on the gut-liver axis can improve the diagnosis and treatment of NAFLD. Objectives.To analyse an association between faecal microbiota and ALAT levels, triglycerides, BMI, and WC in T2DM patients. Material and Methods.Data were collected retrospectively from newly diagnosed T2DM patients included in OPTIMED study from June 2015 until May 2016. Exclusion criteria were: use of antibiotics, antidiabetics, probiotics, immunosuppressants/corticosteroids in the past two months, allergies to the prescribed antidiabetic treatment, chronic gastrointestinal, autoimmune, oncological diseases, kidney or liver function impairment, alcoholism, and diarrhoea during the previous week. Anthropometric measures, blood samples and faecal samples for microbiota analysis were taken. 16S rRNA gene analysis was performed for detecting phyla and genera of the bacteria. Results.11 patients were included in the study, seven of them had increased ALAT (≥29 IU/l for ♂, ≥22 IU/l for ♀).No significant differences were detected between ALAT groups (anthropometric measures,cholesterol,age,alcohol,and sex), as well as no significant differences in faecal microbiota composition at phylum level.At genera level we found significantly higher levels of Coriobacteriaceae_unclassified (p=0.02) and Lachnospiraceae_UCG-010 (p=0.04) in the elevated ALAT group, whereas Coprococcus_1 (p=0.01) and Romboutsia (p=0.01) were more abundant in the normal ALAT group At phylum level SDI correlated negatively with TG (r=-0.800,p=0.003).Bacteroidetes–with WC (r=-0.793,p=0.004) and TG (r=-0.709,p=0.015).Firmicutes - with WC (r=0.706,p=0.015) and TG (r=0.755,p=0.01). At genus level SDI correlated negatively with BMI (r=-0.691,p=0.019).TG–with Ruminococcaceae_UCG-002 (r=-0.618,p=0.04) and Subdoligranulum (r=-0.86,p=0.001).The BMI–with Ruminococcaceae_UCG-004 (r=-0.67,p=0.02),Butyricimonas (r=-0.73,p=0.01), Flavonifractor (r=0.62,p=0.04),Holdemania (r= 0.715,p=0.013).WC–with Holdemania (r=-0.779,p=0.005),Bacteroides (r= 0.688,p=0.019), Parvibacter (r=-0.646,p=0.032), Lactobacillus (r=0.623,p=0.04) and Ruminococcus_2 (r=-0.679;p=0.022).ALAT with [Erysipelotrichaceae] (r=0,61,p=0,04),Romboutsia (r=0.7,p=0.01),Blautia (r=-0.75,p=0.01) and [Eubacterium]_hallii_group (r=-0.62, p=0.04).