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Host-Microbe Interactions: Effects on nutrition and physiology - Dr. Tom Burkey, University of Nebraska-Lincoln, from the 2014 Allen D. Leman Swine Conference, September 15-16, 2014, St. Paul, Minnesota, USA. More presentations at http://www.swinecast.com/2014-leman-swine-conference-material
Citation preview
Host-Microbe Interactions: Effects on nutrition and
physiology
Thomas E. Burkey
September 15, 2014
Allen D. Leman Swine Conference
Outline Introduction Microbial Diversity in the Gut Function of the gut microbiota Composition of gut microbiota is affected by diet “Gut Health” Defined Does health status affect gut microbial community
composition and function? Future Directions
Microbial Diversity in the Gut• The adult human gastrointestinal (GI) tract contains
all three domains of life—bacteria, archaea, and eukaryota.
• Human gut microbiota:
• 100 trillion archaeal and bacterial cells
• Distributed over 1000 species
• Dominated by bacterial species
• The most dominant divisions are the Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria.
Tremaroli & Backhed. Nature: 489, 242–249
Overview of microbial diversity of the human gut
Bäckhed et al., 2005
Host specific gut microbiota composition
Dethlefsen et al., 2007
Function of the gut microbiota Microbiota: collective microbial community inhabiting a
specific environment Microbiome: collective genomic content of a microbiota
(i.e., total genetic capacity of the community) Metagenome: total DNA that can be extracted from an
environment (i.e., aggregate of host DNA and microbiota DNA) Host bacteria, archaea, fungi, and yeasts convert
nutrients and host-derived substrates into various metabolites
Dynamic yet stable Microbiota composition differs in health and disease
Gut microbiota: protein metabolism
Dietary and host-derived (pancreatic juice, mucus, shed epithelial cells) protein is available for microbial fermentation.
Products included beneficial SCFAs and potentially toxic metabolites (e.g., ammonia, phenolic compounds, sulphides)
Vavassori et al. 2009. J. Immunol. 183: 6251.
Gut microbiota: carbohydrate metabolism
Principle products of fermentation: Gases SCFAs
Butyrate Propionate Acetate
Vavassori et al. 2009. J. Immunol. 183: 6251.
Gut microbiota: lipid metabolism
No evidence that ingested lipids are degraded by microbiota
However, dietary lipid is linked to bile acid secretion Bile acids can be transformed into bio-active
metabolites by gut bacteria Key players in primary bile acid deconjugation are
Bifidobacterium sp. and Lactobacillus sp. Bile acid metabolites are ligands for nuclear
hormone receptors (e.g., farnesoid X receptor; FXr) FXr signaling affects many gene targets
Bile acid synthesis/transport; lipid and carbohydrate metabolism, regulation of intestinal innate immunity
Vavassori et al. 2009. J. Immunol. 183: 6251.
Composition of gut microbiota is affected by diet
Enterotype 1, enriched in Bacteroides: associated with diets rich in animal fat/protein
Enterotype 2, enriched in Prevotella: associated with diets rich in carbohydrates
Enterotype 3, enriched in Ruminococcus: not well defined
Arumugam et al., 2011Nature: 473, 174–180
Human Example: Impact of diet in shaping gut microbiota
Comparison of fecal microbiota of European children and children from rural Africa
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14691-6
Nutrient x Health Interactions: Models to explore the effects of gut microbes on porcine health and growth performance
Effect of dam parity on litter performance, transfer of passive immunity, and progeny microbial ecology (Carney-Hinkle et al., 2013)
Effects of diet on growth performance and gut health in healthy pigs DDGS (Tran et al., 2011)
Lactose and yeast-dried milk (Tran et al., 2012)
Chicory (inulin) (Mastromano et al., 2014)
Spray-dried porcine plasma (Tran et al., 2014)
Effects of diet on growth performance and gut health in sick pigs PRRSV PCV2
Effect of corn distillers dried grains with solubles on growth performance and health status indicators in weanling pigs (Tran et al., 2012)
Pigs fed DDGS may have increased microbial similarity and decreased bacterial diversity, as well as reductions in microbial richness
Effects of lactose and yeast-dried milk on growth performance, fecal microbiota, and immune parameters of nursery pigs (Tran et al., 2012)
The effects of lactose and yeast-dried milk on Lactobacillus composition at d 0, 7, and 14 postweaning At weaning (d 0), no differences among treatments for fecal
Lactobacillus staining intensity. At d 7 postweaning, pigs fed lactose with or without yeast-dried milk
had greater (P < 0.05) staining intensity of putative L. johnsonii when compared with the control pigs.
At d 14 postweaning, control pigs had greater putative L. delbrueckii (P < 0.04) and tended to have greater L. sobrius/amylovorus (P = 0.10).
Microbial transmission and assembly of gut microbiota in neonatal pigs on d 7 and 14 postfarrowing.
Hinkle et al. 2011. J. Anim. Sci. 89(E-Suppl. 2): 662. (Abstr.)
Differences in core microbiota between P1 and P3 dams and their progeny.
Hinkle, E.E. et al. 2012. Proc. 12th Int. Symp. Dig. Phys. Pigs. Keystone, CO.
Effects of spray-dried porcine plasma on fecal microbiota in nursery pigs
Ion Torrent profiling sequences target gene based on pH fluctuation during nucleotide chain synthesis
Relative abundance of major phyla (A), families (B), and genera (C) in pigs fed control and SDPP diets across a 4-wk feeding period.
Effects of spray-dried porcine plasma on fecal microbiota in nursery pigs
Feeding SDPP alters fecal microbial communities in pigs May decrease pathogenic
bacteria (e.g., C. difficile, E. rhusiopathiae, B. helcogenes)
May increase cellulose degrading bacteria (e.g., Clostridium sp. and Ruminococcus sp.)
May increase butyric acid-producers (e.g., Lactobacillus sp. and Megasphaera elsdenii)
Distribution of shared OTUs in pigs fed spray-dried porcine plasma compared to control pigs.
“Gut Health” Defined Linking diet, gut enterotypes, and health?? …”a state of physical and mental well-being in the
absence of GI complaints that require the consultation of a doctor, in the absence of indications of or risks for bowel disease and in the absence of confirmed bowel disease”.
Five major criteria for a healthy gut Effective digestion/absorption Absence of GI illness Normal and stable intestinal microbiota Effective immune status Status of well-being
Bischoff, S.C. 2011. ‘Gut Health’: a new objective in medicine? BMC Medicine. 9:24.
“Gut Health”: Underlying Mechanisms
Bischoff, S.C. 2011. ‘Gut Health’: a new objective in medicine? BMC Medicine. 9:24.
Functional entities to maintain Gut Health
GI Microbiome Energy homeostasis Mucosal infection Mitigates immune hypersensitivity Contributes to maintain GI barrier
GI Barrier Epithelial defense Metabolic function Mucosal immune system Enteric nervous system
Microbial markers of dysbiosis
Rajilić-Stojanović, 2013
Does health status affect gut microbial community composition and function? ……….PRRSV model The impact of PPRSv on feed efficiency, digestibility
and tissue accretion in grow-finisher pigs Objective: Characterize the impact PRRSv challenge
has on Feed efficiency, energy and nutrient digestibility Body composition and tissue accretion Post-absorptive metabolism
Hypothesis: The reduction in growth rates during PRRSv infection is associated with reduced energy and nutrient digestibility
Impact of PRRSv on body composition and tissue accretion DXA predicts total mass, lean, fat, and
bone mineral density/content
Effects of PRRSv challenge on Apparent Total Tract Digestibility (ATTD) 21 dpi
65 dpi
How do you explain the long term negative impact on ATTD?
What is the metabolic cost of disease challenge? Energy
Immune response Nitrogen clearance Changes in metabolic rates
Amino Acids Synthesis of immune cells Gluconeogenesis
Metabolic Shift? Up-regulation of glycolysis Amino acids: immune proteins, gluconeogenic
intermediates
Metabolic Shift? Poorer growth
responding pigs to PRRSv Higher blood glycerol,
urea, and lactate Lower blood glucose,
pyruvate and citrate
Pigs that regulate metabolic shifts (oxidative to glycolytic metabolism) may handle immune challenges better? This appears to be
also influenced by genetic selection for disease tolerance
How do you explain the long term negative impact on ATTD? Changes in gut microbial community, metabolites???
Does health status affect gut microbial community composition and function? …….PCV2 model The effects of PCV2 on growth performance of pigs
fed simple vs. complex diets Objective: Characterize the effects of simple vs
complex diets on pigs challenged with PCV2 Hypothesis: Diet complexity will have differential
effects on growth performance of pigs challenged with PCV2 96 barrows; 33 d of age; 7.1 kg initial BW PCV2 status (vaccinated v infected) Diet type (complex, simple, simple + probiotic)
The effect of PCV2 on BW, kg
Overall = 0.061
The effect of diet type on ADG, kg
The effect of diet type on ADFI, kg
Effect of PCV-status and diet type on digestibility…..gut microbial community…..
?
Areas of opportunity Five major criteria for a healthy gut
Effective digestion/absorption Absence of GI illness Normal and stable intestinal microbiota Effective immune status Status of well-being
Can we quantify to further define “Healthy Gut”?
Areas of opportunity Understanding how the diet affects the microbiome
and how the metagenome is affected by diet in both healthy and sick pigs……. Reduced feed intake/digestibility Reduced tissue accretion Long lasting impact on feed efficiency Glycolytic shift may be important
Altered nutrient requirements? Increasing appetite Lowering energetic cost of disease Potential dietary interventions
Areas of opportunity Development of pre- and probiotics?
Synbiotics? Lactobacillus reuteri competition
experiment
Areas of opportunity
Development of a cecum cannulated pig model to evaluate gut microbial community dynamics and function at the molecular and physiological levels Gut Microbial triggers that influence
the disease associated phenotype Can microbial gene expression be
evaluated to understand microbial function?
Allows for repeated real-time monitoring of the gut microbiome
Acknowledgments USDA – Animal Health Formula Funds National Pork Board
Grant# 12-163 Iowa Pork Producers Association
Grant# 12-113 Choice Genetics International Ingredient Corporation Drs. Gabler, and Odle, laboratory staff and students Drs. Miller, Fernando, Walter, and Hostetler, laboratory staff and
students