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

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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.

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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)

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EQUILIBRUM - BALANCED
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• Important host factors in maintaining mucosal
  health
• Mucus and secreted compounds
• Intestinal epithelial integrity
• Immune cells

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Mucus and secreted compounds
OPTIMAL
POOR
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Intestinal epithelial integrity
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Intestinal epithelial integrity
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Inflammation TLR and NOD-driven signalling
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TLR activation and induction of inflammation
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EQUILIBRUM - BALANCED
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ENVIRONMENT
HOST
MICROBIOTA
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Global gut microbiota composition
Optimal Poor (intestinal health)
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Proteobacteria

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

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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?

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105-107cfu/g
Ingestion of sugars (poly-, oligo, mono-)
Monosaccharide transporters
Saccharolytic fermentation
SCFA absorption
1010-1011cfu/g
Proteolytic fermentation
101-102cfu/g
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Polysaccharides Oligosaccharides Monosacchari
des
Bacteroidetes, lactobacilli, bifidobacteria,
Lactate, acetate H2
Methanogenic bacteria (Archaebacteria)
SO42-
Firmicutes Clostridium cluster IX
H2S CH4
Propionate
Firmicutes Clostridium cluster IV and XIVa
Proteobacteria Sulphate reducers (SRB), e.g.
Desulfovibrio Also Enterobacteraceae
Butyrate
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Butyrate and Salmonella how a small molecule can
shift the host-pathogen interaction
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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
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Caecal colonization
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Why is butyric acid decreasing Salmonella
colonization?
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Effect acids on invasion of Salmonella !
Zowel voor Salmonella Enteritidis als Typhimurium
Data from invasion assay in cultured epithelial
cells in vitro
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Effect of acids on hilA expression
Direct effect of butyrate on bacterial metabolism
and virulence bacterial cross-talk
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Butyrate producers
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Rat colitis model
B. pullicaecorum
Positive control
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Effect on necrotic enteritis
d16 d17 d18 d19 d20 d21 d22 d23 d24
Gumboro vaccine x
Feed 30 fishmeal x x x x x x x
10-fold dose of Paracox-5 x
oral inoculation with C. perfringens strain 56 x x x x
Autopsy x x x
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Effect on necrotic enteritis
Percentage animals having lesions ()
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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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2 - 8
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2 - 8
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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
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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

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