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How to manipulate the communication between the gut microbiota and the gut mucosa to improve intestinal health: the case

How to manipulate the communication between the gut microbiota and the gut mucosa to improve intestinal health: the case of butyrate. Prof. Dr. Filip Van Immerseel Faculty of Veterinary Medicine, Department of Pathology, Bacteriology and Avian Diseases

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How to manipulate the communication between the gut microbiota and the gut mucosa to improve intestinal health: the case

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  1. How to manipulate the communication between the gut microbiota and the gut mucosa to improve intestinal health: the case of butyrate Prof. Dr. Filip Van Immerseel Faculty of Veterinary Medicine, Department of Pathology, Bacteriology and Avian Diseases 3rd International Fresenius Conference, February 13-14th, Cologne, Germany.

  2. ENVIRONMENT HOST MICROBIOTA What is ‘good intestinal health’? A healthy gut is a gut in which the environment is regulated as such that a stable and constant condition of properties is maintained (homeostasis)

  3. ENVIRONMENT HOST MICROBIOTA EQUILIBRUM - BALANCED

  4. Important host factors in maintaining mucosal health: • Mucus and secreted compounds • Intestinal epithelial integrity • Immune cells

  5. Mucus and secreted compounds OPTIMAL POOR

  6. Intestinal epithelial integrity

  7. Intestinal epithelial integrity

  8. Inflammation: TLR and NOD-driven signalling

  9. TLR activation and induction of inflammation

  10. ENVIRONMENT HOST MICROBIOTA EQUILIBRUM - BALANCED

  11. ENVIRONMENT HOST MICROBIOTA

  12. Global gut microbiota composition Optimal Poor (intestinal health)

  13. Proteobacteria • Enterobacteraceae: TLR5 activation and inflammation (ao. pathogens such as Salmonella) • SRB (H2S producers): toxic effect on epithelial cells, block butyrate oxidation

  14. Butyrate • Inhibits NFkB activation and inflammation • Induces AMP expression, and mucin expression • Acts trophic for epithelial cells • Induces TJ expression • … Thus butyrate is essential for gut health? Thus butyrate producing bacteria need to be abundant in the gut to promote gut health?

  15. 105-107cfu/g Ingestion of sugars (poly-, oligo, mono-) Monosaccharide transporters Saccharolytic fermentation SCFA absorption 1010-1011cfu/g Proteolytic fermentation 101-102cfu/g

  16. Polysaccharides Oligosaccharides Monosaccharides Bacteroidetes, lactobacilli, bifidobacteria, … Lactate, acetate H2 Methanogenic bacteria (Archaebacteria) Firmicutes Clostridium cluster IX SO42- H2S CH4 Propionate Firmicutes Clostridium cluster IV and XIVa Proteobacteria Sulphate reducers (SRB), e.g. Desulfovibrio Also Enterobacteraceae Butyrate

  17. Butyrate and Salmonella: how a small molecule can shift the host-pathogen interaction

  18. What is the effect of SCFA on Salmonella? Five groups of 20 chickens : CTRL FORMIC ACETIC PROPIONIC BUTYRIC ALL ACIDS COATED ON BEADS !! Infection at day 5 with 5.10³ cfu S. Enteritidis Euthanasia at day 8 Bacteriological analysis of caeca, liver and spleen : titration on BGA

  19. Caecal colonization

  20. Why is butyric acid decreasing Salmonella colonization?

  21. Effect acids on invasion of Salmonella ! Zowel voor Salmonella Enteritidis als Typhimurium Data from invasion assay in cultured epithelial cells in vitro

  22. Effect of acids on hilA expression Direct effect of butyrate on bacterial metabolism and virulence: bacterial cross-talk

  23. Butyrate producers

  24. Rat colitis model B. pullicaecorum Positive control

  25. Effect on necrotic enteritis

  26. Effect on necrotic enteritis Percentage animals having lesions (%)

  27. Abundance of butyrate producing Clostridium cluster IV and XIVa and Proteobacteria in dysbacteriosis? Dysbiosis: ‘Trendy’ term pointing to a condition in which composition of microbiota is capable of decreasing performance due to poorly described mechanisms, although pathogens are not necessarily present Synonyms ??? Feed passage syndrome Malabsorption syndrome Wet litter syndrome …..

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  29. 2 - 8

  30. Abundance of butyrate producing Clostridium cluster IV and XIVa and Proteobacteria in dysbacteriosis? High dysbiosis score Low dysbiosis score Effect of butyrate on host functions: intra-species communication

  31. Conclusions • Stimulation of butyrate producing Cluster IV and XIVa bacteria can be beneficial to: • Reduce pathogen colonization • Decrease inflammation • Increase gut health • As a consequence improve performance

  32. How to stimulate caecal butyrate production? SUBSTRATE Prebiotics Feed Probiotics PRODUCERS

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