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GUT MICROBES
AND GUT
DISEASE:
INFLAMMATORY
BOWEL DISEASE
SANDRA UNORJI
BIOT 5530
INSTRUCTOR: DR.
SANTIAGO-
VAZQUEZ
1
Introduction
• You harbor 100 trillion microbes
2
What are Gut Microbes?
Microbes found in the
digestive tract
10-20 trillion cells
Not fully known
90-99% are bacterial.
3
How are They Classified?
Firmicutes
Bacteroidetes
Actinobacteria
Proteobacteria
4
What’s Their Job?
Gut Bacteria Abundant Species Functions
Firmicutes Lactic Acid Bacteria spp,
Clostridia spp
Probiotics, ferment complex
carbohydrate, prevents
translocation of bacteria
Bacteroidetes Bacteroides spp Protects epithelial wall and
develop immune system.
Actinobacteria Bifidobacteria spp Probiotics, Protects host
epithelial cells
Proteobacteria E.coli, Helicobacter
species
Protect microbes against
pathogens and in binding to
intestinal tract
5
Table 1. Roles of Gut bacteria
Gut Microbiome at Different Stages of
Life
6Kumar et al., 2016
Gut Microbes and Disease
Do they play a role?
Inflammatory Bowel Disease (IBD)
• Abnormal immune response
leading to inflammation of
intestinal tract.
• Symptoms: Diarrhea, weight loss,
abdominal pain.
• Types:
• Ulcerative colitis
• Crohn’s disease
8
Inflammatory Bowel Disease (IBD)
• One of the major cause of
inflammation is an alteration in
the microflora
9
Giovanni A, 2016
Phylogenetic analysis of Microbiome in
IBD
10
Frank et. al.
2007.
NI: Non-IBD
UC: Ulcerative Colitis
CD: Chron’s Disease
CON SUB: Control
Subject
IBD SUB: IBD Subject
Insights from IBD study with mice
• Proteobacteria, E.coli was
inoculated in IL-10-/- germ
free mice and wild type mice
as control.
• Inflammation was induced in
both mice samples.
11Kim et al, 2005. Sections of the intestine (A) Wild type mice (D) IL-10 -/- germ free mice
Treatment of IBD Using Gut Microbes
12
Restoration
of
Microbiome
Pre-biotics
Fecal
Microbial
Transplant
Pro-biotics
Treatment of IBD using Gut Microbes
• Pre-biotics: Nutritional substrate used to promote the growth of
potentially beneficial microbes
• Pro-biotics: Live organisms used improve microbial diversity
• Fecal Microbial Transplant: Transfer of fecal bacteria or feces
from a healthy donor to a recipient
• Studies have shown increase in gut microbial diversity and
corresponding improvement of IBD in clinical trials and mouse
models
13
Prebiotics: Fructo-oligosaccharide in
Clinical trial
• In a clinical trial, Fructo-
oligosaccharide was
supplemented in diet of
IBD patients for 3 weeks
• Increase in bacteria led to a
subsequent reduction in
disease activity
14Lindsay, J. O(2006). (A) Microbial Diversity (B) Response to Treatment
A
B
Probiotics: Lactococcus lactis in Mouse
model
• Lactic acid bacteria, Lactococcus
lactis was engineered to secrete
cytokine IL-10 needed to
regulate inflammation.
• 50% reduction in ulcerative colitis
15
Steidler, L., et al. (2000)
Fecal Microbial Transplant: Clinical
Trial
• Treatment rate was 91.8%
in patients with fecal
transplant after 10 weeks.
• Microbiome of patient
looked like that of the
healthy donor
16Van N, et al. (2013)
MicrobialDiversityTreatmentResponse
Conclusion
Gut microbes play
significant roles in
both human
health and
disease.
01
Manipulation of these
microbes has great
potential as a
therapeutic option.
02 03
Current studies are
focusing on building
a catalogue of
human gut
microbiome for
better diagnosis.
References
• Cantarel, B.L., Lombard V., Henrissat B. (2012). Complex Carbohydrate Utilization by the Healthy Human
Microbiome. Appanna VD, ed. PLoS ONE.7(6):e28742.
• Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007). Molecular-
phylogenetic characterization of microbial community imbalances in human inflammatory bowel
diseases. Proceedings of the National Academy of Sciences of the United States of America, 104(34), 13780–
13785.
• Kim, Sandra C. et al. (2005). Variable phenotypes of enterocolitis in interleukin 10-deficient mice
monoassociated with two different commensal bacteria. Gastroenterology,128(4), 891 - 906
• Larry S. (2013). Comparison of Microbial Communities in Healthy and IBD patients. Institute Director at
California Institute for Telecommunications and Information Technology. Retrieved 22 Nov. 2017.
• Lindsay, J. O., Whelan, K., Stagg, A. J., Gobin, P., Al‐Hassi, H. O., Rayment, N., … Forbes, A. (2006). Clinical,
microbiological, and immunological effects of fructo‐oligosaccharide in patients with Crohn’s disease. Gut, 55(3),
348–355. http://doi.org/10.1136/gut.2005.074971
• Nanjundappa, R. H., Ronchi, F., Wang, J., Clemente-Casares, X., Yamanouchi, J., Umeshappa, C. S.,
Santamaria, P. (2017). A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis. Cell,
171(3).
• Steidler, L., W. Hans, L. Schotte, S., Neirynck, F. Obermeier, W. Falk, W., Fiers, and E. Remaut. (2000).
Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science, 289:1352–1355.
• Van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman
JF, Tijssen JG et al. 2013. Duodenal infusion of donor feces for recurrent clostridium difficile. N Engl J Med.
368(5):407-415.
• Wu, H.-J., & Wu, E. (2012). The role of gut microbiota in immune homeostasis and autoimmunity. Gut
18
THANK YOU!!!
19

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Impact of gut microbes on gastrointestinal disease

  • 1. GUT MICROBES AND GUT DISEASE: INFLAMMATORY BOWEL DISEASE SANDRA UNORJI BIOT 5530 INSTRUCTOR: DR. SANTIAGO- VAZQUEZ 1
  • 2. Introduction • You harbor 100 trillion microbes 2
  • 3. What are Gut Microbes? Microbes found in the digestive tract 10-20 trillion cells Not fully known 90-99% are bacterial. 3
  • 4. How are They Classified? Firmicutes Bacteroidetes Actinobacteria Proteobacteria 4
  • 5. What’s Their Job? Gut Bacteria Abundant Species Functions Firmicutes Lactic Acid Bacteria spp, Clostridia spp Probiotics, ferment complex carbohydrate, prevents translocation of bacteria Bacteroidetes Bacteroides spp Protects epithelial wall and develop immune system. Actinobacteria Bifidobacteria spp Probiotics, Protects host epithelial cells Proteobacteria E.coli, Helicobacter species Protect microbes against pathogens and in binding to intestinal tract 5 Table 1. Roles of Gut bacteria
  • 6. Gut Microbiome at Different Stages of Life 6Kumar et al., 2016
  • 7. Gut Microbes and Disease Do they play a role?
  • 8. Inflammatory Bowel Disease (IBD) • Abnormal immune response leading to inflammation of intestinal tract. • Symptoms: Diarrhea, weight loss, abdominal pain. • Types: • Ulcerative colitis • Crohn’s disease 8
  • 9. Inflammatory Bowel Disease (IBD) • One of the major cause of inflammation is an alteration in the microflora 9 Giovanni A, 2016
  • 10. Phylogenetic analysis of Microbiome in IBD 10 Frank et. al. 2007. NI: Non-IBD UC: Ulcerative Colitis CD: Chron’s Disease CON SUB: Control Subject IBD SUB: IBD Subject
  • 11. Insights from IBD study with mice • Proteobacteria, E.coli was inoculated in IL-10-/- germ free mice and wild type mice as control. • Inflammation was induced in both mice samples. 11Kim et al, 2005. Sections of the intestine (A) Wild type mice (D) IL-10 -/- germ free mice
  • 12. Treatment of IBD Using Gut Microbes 12 Restoration of Microbiome Pre-biotics Fecal Microbial Transplant Pro-biotics
  • 13. Treatment of IBD using Gut Microbes • Pre-biotics: Nutritional substrate used to promote the growth of potentially beneficial microbes • Pro-biotics: Live organisms used improve microbial diversity • Fecal Microbial Transplant: Transfer of fecal bacteria or feces from a healthy donor to a recipient • Studies have shown increase in gut microbial diversity and corresponding improvement of IBD in clinical trials and mouse models 13
  • 14. Prebiotics: Fructo-oligosaccharide in Clinical trial • In a clinical trial, Fructo- oligosaccharide was supplemented in diet of IBD patients for 3 weeks • Increase in bacteria led to a subsequent reduction in disease activity 14Lindsay, J. O(2006). (A) Microbial Diversity (B) Response to Treatment A B
  • 15. Probiotics: Lactococcus lactis in Mouse model • Lactic acid bacteria, Lactococcus lactis was engineered to secrete cytokine IL-10 needed to regulate inflammation. • 50% reduction in ulcerative colitis 15 Steidler, L., et al. (2000)
  • 16. Fecal Microbial Transplant: Clinical Trial • Treatment rate was 91.8% in patients with fecal transplant after 10 weeks. • Microbiome of patient looked like that of the healthy donor 16Van N, et al. (2013) MicrobialDiversityTreatmentResponse
  • 17. Conclusion Gut microbes play significant roles in both human health and disease. 01 Manipulation of these microbes has great potential as a therapeutic option. 02 03 Current studies are focusing on building a catalogue of human gut microbiome for better diagnosis.
  • 18. References • Cantarel, B.L., Lombard V., Henrissat B. (2012). Complex Carbohydrate Utilization by the Healthy Human Microbiome. Appanna VD, ed. PLoS ONE.7(6):e28742. • Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007). Molecular- phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America, 104(34), 13780– 13785. • Kim, Sandra C. et al. (2005). Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology,128(4), 891 - 906 • Larry S. (2013). Comparison of Microbial Communities in Healthy and IBD patients. Institute Director at California Institute for Telecommunications and Information Technology. Retrieved 22 Nov. 2017. • Lindsay, J. O., Whelan, K., Stagg, A. J., Gobin, P., Al‐Hassi, H. O., Rayment, N., … Forbes, A. (2006). Clinical, microbiological, and immunological effects of fructo‐oligosaccharide in patients with Crohn’s disease. Gut, 55(3), 348–355. http://doi.org/10.1136/gut.2005.074971 • Nanjundappa, R. H., Ronchi, F., Wang, J., Clemente-Casares, X., Yamanouchi, J., Umeshappa, C. S., Santamaria, P. (2017). A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis. Cell, 171(3). • Steidler, L., W. Hans, L. Schotte, S., Neirynck, F. Obermeier, W. Falk, W., Fiers, and E. Remaut. (2000). Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science, 289:1352–1355. • Van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG et al. 2013. Duodenal infusion of donor feces for recurrent clostridium difficile. N Engl J Med. 368(5):407-415. • Wu, H.-J., & Wu, E. (2012). The role of gut microbiota in immune homeostasis and autoimmunity. Gut 18