Human microbiota, Intestinal microbiota, Composition of human microbiota, Enterotypes, Human microbiota through life stages, Neural networks in intestinal immunoregulation, Reciprocal interactions of the intestinal microbiota and immune system, Interactions between commensal intestinal bacteria and the immune system, Host microbe interaction in homoeostasis, Host microbe interaction in inflammation, Microbiota and association with extraintestinal diseases, Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination, Normal gut microbiota modulates brain development and behavior, Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome, Study on the changes of intestinal flora accociated with the posterior lumbar spine surgery, Intervention by shaping intestinal microbiota?, Genetic predisposition and microbiota, Aims and objectives, Endotoxicity of Lipopolysaccharide as a Determinant of T-Cell – Mediated Colitis Induction in Mice, The structural basis of LPS recognition by the TLR4-MD2 complex, Isolated low endotoxic LPSMUT protects from colitis, Low endotoxic LPS, a microbial symbiosis factor, Perspectives, What is needed for your patients?, Conclusion

1. Microbiota changes in the neurogenic gut
Julia-Stefanie Frick
Institut für Medizinische Mikrobiologie und Hygiene
Universitätsklinikum Tübingen
Eberhard Karls-Universität Tübingen

2. Human microbiota

3. Intestinal microbiota

4. Composition of human microbiota
B. Sartor Gastroenterology 2008

5. Arumugam et al. Nature 473, 174-180, 2011
Enterotypes

6. Human microbiota through life stages

10. RB Sartor Gastroenterology. 2008 Feb;134(2):577-94.
Host microbe interaction in homoeostasis

11. RB Sartor Gastroenterology. 2008 Feb;134(2):577-94.
Host microbe interaction in inflammation

12. Willing BP, Russell SL, Finlay BB.
Nat Rev Microbiol. 2011 Apr;9(4):233-43.
Microbiota and association with extraintestinal diseases

14. 14

17. Intervention by shaping intestinal microbiota?
Fecal Transplantation?Probiotics?Prebiotics?

18. Genetic predisposition and microbiota
Riscs?

19. Aims and objectives
α
defensins
M cells
DC
DC
DC
Treg
TH1
TH17
IL-10
IL-10
TGFβ
IL-10
TGFβ
Microbiota
Bacterial compounds and host target cells maintaining intestinal immune balance
Novel therapeutic substances and targets in treating IBD

20. Endolo
Endohi
Low endotoxicity
High endotoxicity
Gastroenterology. 2013 Nov 21. pii: S0016-5085(13)01711-3. doi: 10.1053/j.gastro.2013.11.033. [Epub ahead of print]
Relative abundance of phyla of intestinal bacteria:
HEK TLR4/MD2

21. Endolo: No Colitis
Endohi: Colitis
Histology score:
Gastroenterology. 2013 Nov 21. pii: S0016-5085(13)01711-3. doi: 10.1053/j.gastro.2013.11.033. [Epub ahead of print]
Low endotoxic microbiota
protects Rag1-/- mice from
T cell transfer colitis

22. Park et al. Nature. 2009
The structural basis of LPS recognition by the TLR4-MD2 complex
Activity of Lipid A determined by:
 Number and location of phosphate groups
 Number of fatty acid chains
 Chemical structure of the lipid chains
Lipid A of LPS mediates the endotoxic effect
Park et al. Nature. 2009

23. Isolated low endotoxic LPSMUT protects from colitis
LPSMUT does not promote TH1/TH17 responses  PROTECTS FROM COLITIS
Gastroenterology. 2013 Nov 21. pii: S0016-5085(13)01711-3. doi: 10.1053/j.gastro.2013.11.033. [Epub ahead of print]

24. High endotoxic LPSWT promotes inflammation
Low endotoxic LPSMUT promotes homoeostasis
Danger Signal
Homoeostasis Factor
LPS structure decides on maintenance of homoeostasis
or induction of inflammation
Low endotoxic LPS, a microbial symbiosis factor

25. Multiple Scleosis
Autism
Depression
Asthma
Arteriosklerosis
Obesity
Infections
Inflammatory
bowel diseases
Colonization with
resistant bacteria
Diabetes
Understanding of pathogenesis  Novel therapeutic options
Perspectives

26. What is needed for your patients?
Human studies analysing microbiome and metagenome in neurogenic gut patiens
Novel options in
treatment of
neurogenic gut
Problems:
 Diversity
 Age of patient
 Medication
 Antibiotics
 Nutrition
Chances:
 Understanding of pathogenesis
 Understanding of host-microbe
interaction
 Correlations of symptoms /problems with
presence of specific phyla
 Specific modulation of the microbiota
composition

27. Conclusion
Lots of work to do…

28. Thank you
Workgroup Frick:
Anna Lange
Sarah Menz
Isabell Flade
Ali Giray Korkmaz
Kerstin Gronbach
Thorsten Kliem
Raphael Parusel
Andrea Schäfer
Alexander Steimle
Annika Bender
Todor Popov
Sebastian Sennock
Christine Niemeyer
Ingo B. AutenriethCooperations
Patrick Adam, Tübingen
Lena Alexopoulu, Marseille
Konrad Bode, Heidelberg
Sean Colgan, Denver
Ulrich Dobrindt, Münster
Paul Enck, Tübingen
Friedrich Götz, Tübingen
Klaus Hantke, Tübingen
Otto Holst, Borstel
Daniel Huson, Tübingen
Hubert Kalbacher, Tübingen
Funding:
GRK 1708
SPP 1656
SFB 766
Karsten Kristiansen, Copenhagen
Antonio Molinaro, Naples
Tobias Ölschläger, Würzburg
Bernd Pichler, Tübingen
Sandra Schwarz, Tübingen
Klaus Schulze-Osthoff, Tübingen
Barbara Stecher, Munich
Sebastian Suerbaum, Hannover
Sören Schubert, Munich
David Vöhringer, Erlangen