Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Resemann, L.
Crosstalk and interaction between gut microbiota and bile acids
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp. 84
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fickert Peter
- Moustafa Tarek
- Altmetrics:
- Abstract:
- Background Research on the interaction between bile acids and microbiota is currently experiencing a zestful renaissance. Microbiota are exposed heavily to bile acids in the colon. This interaction has physiologic implications as the gut microbiota clearly impact on the host's metabolism. Moreover, dysbiosis (a pathologic deviation from a normal microbiota composition) is strongly associated with obesity, type 2 diabetes or chronic cholestasis. In the sense of bilateralism, the host's bile acid profile is modulated by gut microbiota and vice versa. Hence, bile acids are an important determinant of microbiota diversity and function. Methods The interaction between bile acids and microbiota has been investigated with in vitro experiments. For this purpose, two different growth media (LB and GIM) have been prepared, which were supplemented with conjugated, free and artificial bile acids. Microbiota from the caecum of female, male, SHAM and BDL mice have been obtained and cultured in an aerobic and anaerobic environment. The impact of bile acids on bacterial growth was determined via CFU/ml and OD600. Furthermore, the activity of the bacterial enzymes bile salt hydrolase (BSH) and 7a-dehydroxylase has been investigated. Therefore, the formation of free and dehydroxylated (secondary) bile acid derivatives in the cultures was measured via LC-MS. Moreover, we investigated, whether the cultures yielded bacterial metabolites which are capable of modulating hepatic expression of genes of the bile acid metabolism. HepG2 cells were incubated with supernatants of the bacterial cultures and the expression of Cyp7a1 and Shp was quantified via RT-PCR. Results Bile acids inhibit bacterial growth of gut microbiota to a varying extent. CA showed the strongest effect of growth inhibition in LB and GIM. The conjugated bile acids TCA and TUDCA showed attenuated growth inhibition. The semi-synthetic bile acid CHS showed a strong suppression of bacterial growth in GIM, but not in LB. Moreover, CA and TCA in LB showed a stronger growth suppression of bacteria from SHAM mice than of bacteria from BDL mice. TUDCA did not show this effect. Furthermore, bacterial biotransformation of bile acids in vitro is possible, but only the first step, bile acid deconjugation (BSH activity), was performed sufficiently in both, aerobic and anaerobic conditions. Consequent generation of secondary bile acids (7a-dehydroxylation) was neither observed in aerobic nor in anaerobic conditions. Additionally, we were able to show a transactivation of hepatic genes, by metabolites of bacterial cultures in bile acid media. Cyp7a1 expression was repressed under CA, TCA and UDCA. Shp expression was induced under CA and TCA. Bile acids alone do not affect hepatic gene expression (except for CDCA). Conclusion The interaction between bile acids and gut microbiota is complex. Bile acids and their metabolism through gut microbiota contribute to intestinal and hepatic homeostasis.