Funktionen und metabolische Adaptation von dominanten Darmbakterien der Familie Coriobacteriaceae im Kontext des Lipidmetabolismus des Wirtes
Zusammenfassung der Projektergebnisse
The overall aim of this project was to study the impact of dominant gut bacteria within the family "Coriobacteriaceae" (phylum Actinobacteria) on host metabolic health and to study functional adaptations of the microbial communities to dietary interventions. A new gnotobiotic mouse model for in vivo assessment of the role of Coriobacteriaceae was established and used with success in mechanistic studies. We also established a novel bioanalytical platform (HPLC-MS/MS) for targeted measurement of bile acids in various human and mouse body fluids. Two main feeding trials were conducted in mice: In the first study, we observed a substantial impact of Coriobacteriaceae on white adipose tissues when mice were fed primary bile acids: colonized mice were characterized by a 2-fold increase in fat mass. Major other readouts included the metabolic status of mice, bacterial colonization, lipids and bile acids profiles, white adipose tissue proteomes, liver pathophysiology and immune responses. This study delivered the first mechanistic data demonstrating a causal role of Coriobacteriaceae in regulating host metabolic responses compared with association data from the literature. The study is still ongoing to unravel underlying mechanisms and thus not yet published. In the second study, we performed follow-up experiments in which dietary supplementation with primary bile acids was combined with fat enrichment from different fat sources (lard or palm oil) in order to boost the phenotype previously observed in white adipose tissues. In this experiment, we observed remarkable differential effects of the two high-fat diets in control germfree vs. conventional mice, revealing an interplay between diet composition and colonization status for regulation of metabolic responses. In combination with bile acids, dietary lard fed to male C57BL/6 mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germfree mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and mono-unsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of "Lachnospiraceae" and increased occurrence of Desulfovibrionaceae" and the species Clostridium "lactatifermentans" and "Flintibacter butyricus". Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism.
Projektbezogene Publikationen (Auswahl)
- High-fat diet alters gut microbiota physiology in mice. ISME Journal, Vol. 8, 2014, pp. 295–308.
Daniel, Moghaddas Gholami, Berry, Desmarchelier, Hahne, Loh, Mondot, Lepage, Rothballer, Walker, Böhm, Wenning, Wagner, Blaut, Schmitt-Kopplin, Kuster, Haller, Clavel
(Siehe online unter https://doi.org/10.1038/ismej.2013.155) - Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance. Gut Microbes, Vol. 5, 2014, Issue 4, pp. 544-551.
Thomas Clavel, Charles Desmarchelier, Dirk Haller, Philippe Gérard, Sascha Rohn, Patricia Lepage, Hannelore Daniel
(Siehe online unter https://doi.org/10.4161/gmic.29331) - 52. Wissenschaftlicher Kongress der Deutschen Gesellschaft für Ernährung; LC-MS/MS-Multimethode zur Quantifizierung von Cholesterol und Cholesterol-Derivaten aus biologischen Matrices; 11-13 March 2015, Halle/Saale, Germany
Wegner et al.
- Metabolomic Profiling: LC-MS/MS-Multimethode zur Quantifizierung von Hydroxysterolen und Gallensäuren aus biologischen Matrices. Deutsche Lebensmittel-Rundschau, Vol. 111.2015, pp. 198-203.
Philipp Werner, Katrin Wegner, Clara John, Anna Worthmann, Ludger Scheja, Jörg Heeren, Sascha Rohn, Markus Fischer
- (2016) Mining gut microbiome oligopeptides by functional metaproteome display. Scientific Reports, Vol. 6. 2016, Article number: 34337.
Zantow, Just, Lagkouvardos, Lepage, Clavel, Hust
(Siehe online unter https://dx.doi.org/10.1038/srep34337) - 10th Joint Symposium of the Institut National de la Recherche Agronomique (INRA) and The Rowett Institute of Nutrition and Health (RRI); Gut-derived Coriobacteriaceae increase white adipose tissue deposition in mice; 20-23 June 2016, Clermont-Ferrand, France
Clavel et al.
- 53. Wissenschaftlicher Kongress der Deutschen Gesellschaft für Ernährung; Gut-derived Coriobacteriaceae increase white adipose tissue deposition in mice; 02-04 March 2016, Fulda, Germany
Wegner et al.
- 9th Seeon Conference “Microbiota, Probiota and Host”; Gut-derived Coriobacteriaceae increase white adipose tissue deposition in mice; 24-26 June 2016, Seeon, Germany
Just et al.
- 5th Joint Conference of the DGHM and VAAM; Gut-derived Coriobacteriaceae increase white adipose tissue deposition in mice; 05-08 March 2017, Würzburg, Germany
Just et al.
- Rapid analysis of bile acids in different biological matrices using LC-ESI-MS/MS for the investigation of bile acid transformation by mammalian gut bacteria. Analytical and Bioanalytical Chemistry, Volume 409. 2017, Issue 5, pp 1231–1245.
Wegner, Just, Gau, Mueller, Gérard, Lepage, Clavel, Rohn
(Siehe online unter https://doi.org/10.1007/s00216-016-0048-1) - The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism. Microbiome, Vol. 6. 2018, Article number: 134.
Just, Mondot, Ecker, Wegner, Rath, Gau, Hery-Arnaud, Schmidt, Lesker, Bieth, Dunkel, Strowig, Hofmann, Haller, Liebisch, Gérard, Rohn, Lepage, Clavel
(Siehe online unter https://doi.org/10.1186/s40168-018-0510-8)
