Complex interactions between the gut and nutrition from a practical swine production perspective
Thomas E. Burkey Jefo Swine & Poultry Tour 2016
Outline
Introduction “Gut Health” Defined Function of the gut microbiota Feed additives and their interactions Future Directions
2011 Feed efficiency survey of current knowledge (Flohr et al., 2014)
Survey questions asked to determine/identify: Industry level of knowledge related to feed efficiency topics Production practices being used that influence feed efficiency Information gaps or areas requiring additional knowledge to further improve feed efficiency Target subjects were individuals (producers, consultants, academia, etc.) with occupations in the swine industry 205 respondents
Which Topic Areas Provide the Largest Opportunity to Further Improve Feed Efficiency? (1=Important, 10=Least important)
Rank the Following Items on the Need for Future Research as It Pertains to Feed Efficiency (1=Important, 10=Least important)
Rank Your Level of Knowledge on the Following Areas as They Pertain to Feed Efficiency (1=Knowledgeable, 10=Need more information)
2011 Feed efficiency survey of current knowledge (Flohr et al., 2014)
Conclusions Areas providing greatest opportunity for feed efficiency: Genetics, Health, Feed Processing, Dietary Energy Topic areas where respondents were least knowledgeable: Expanding/extruding technologies, Gut microbiology, and feed additives (other than antibiotics)
Network of interactions
PLoS Pathog. 2011 Dec; 7(12): e1002223.
Gut Health
Critical design paradox?
“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 Digestive and Barrier Functions Bischoff, S.C. 2011. ‘Gut Health’: a new objective in medicine? BMC Medicine. 9:24.
“Gut Health”: Underlying Mechanisms
GI contribution to health not limited to nutrient assimilation/metabolism Animal and human experiments have shown that: 1.Gut communicates with bacteria that support digestion by enzymatic capacity 2.Gut regulates major epithelial/immune functions for gut health and health in general 3.Gut reports to the brain via the N. vagus and hormones about energy uptake and conditions that might affect mood and general well-being 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
Measurement of Digestive/Absorptive Function as indicators of Gut Health
Functional
Digestibility Trials Nutrient Transport
Electrophysiological measurements
Performance ADG G:F
Descriptive
Histomorphometry
Villus height/surface area
Nutrient Transport expression
SGLT, AA transporters
Brush border enzyme analysis
**Commercial Production vs Research Environment? **Functional and Descriptive measurements are not always in agreement!
Adam Moeser, Michigan State University
Function of the gut microbiota
Host bacteria, archaea, fungi, and yeasts convert nutrients and host-derived substrates into various metabolites Dynamic yet stable Metagenome: microbial metabolites are health promoting Microbiota composition differs in health and disease
Gut microbiota: carbohydrate metabolism
Principle products of fermentation: Gases SCFAs Butyrate Propionate Acetate
Vavassori et al. 2009. J. Immunol. 183: 6251.
Gut microbiota: protein metabolism
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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: 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.
Types of feed additives
Antibiotics Acidifiers Anthelmintics Carbohydrate-degrading enzymes/proteases Carcass modifiers Flavors High dietary levels of Cu and Zn Mold inhibitors, mycotoxin binders, antioxidants Phytase Phytogenics Probiotics, prebiotics, synbiotics
J Swine Health Prod. 2009;17(5):270–275.
Feed Enzymes
Modes of Action Degradation of bonds not usually hydrolyzed by endogenous enzymes. Degradation of antinutritional factors that limit digestion directly Disruption of endosperm integrity Shift of digestion to more efficient digestion sites Reductions in endogenous secretions and protein losses from the gut Changes in the intestinal morphology Changes in the microflora profile in the small intestine Augmentation of endogenous digestive enzymes
J Appl Poult Res (2013) 22 (3): 628-636.
Feed enzymes
J Appl Poult Res (2013) 22 (3): 628-636.
Protease and Xylanase
Some inconsistency in research and field results Digestibility data variable on improved digestibility of N, GE, fiber (when present, often ~2-3%) Application to commercial diets? Do enzymes compete for substrate directly/indirectly? Great area of opportunity with continued R&D support Is there a physiologic limit? Joel DeRouchey, Kansas State University personal communication
Prebiotics, Probiotics, Synbiotics
Probiotic modes of action Barrier function Adhesion Antagonism Antimicrobial Immunomodulation Gene expression?
Ann Nutr Metab 2012;61:160–174 (DOI:10.1159/000342079)
Identifying probiotics isolated from prebiotic-fed pigs
64 crossbred pigs (initial BW = 6.6 kg), 20 to 22 d postfarrowing 4 pigs (2 barrows and 2 gilts) per pen; 4 pens per treatment 4 dietary treatments were fed for 2 Phases (d 0 to 14 and d 14 to 28 postweaning): 1) Control 2) Control + 0.1% chicory (inulin-type fructans) 3) Control + 0.1% mannan oligosaccharides (MOS) 4) Control + 0.02% chitosan Li et al. 2016 J. Anim. Sci (abstract)
Identifying probiotics isolated from prebiotic-fed pigs
Identifying probiotics isolated from prebiotic-fed pigs
Identifying probiotics isolated from prebiotic-fed pigs 
Correlations of OTU abundances to phenotypic traits using MaAsLin analysis
Probiotic efficacy review Simon et al. (2003)
44 Published experiments Numerical improvement in ADG observed in >70% of experiments 6.8% of experiments reported improvements in ADG that were statistically significant Inconsistency of responses may be partially explained by use of different strains What is the target phenotype?
Organic acids Modes of action Decreasing stomach pH Inhibition of pathogenic bacteria Energy source Mineral utilization Endogenous enzyme secretion and gut morphology Performance and nutrient utilization Gut microbes? Immune response?
Costa et al., 2013. S. Afr. J. Anim. Sci. vol. 43
Organic acids (Acidifiers)
Tung and Pettigrew (Critical Review of Acidifiers – NPB #05169) Significant increase in growth rate of pigs 0 to 2 wk (12% on average) 0 to 4 wk (6% on average) Improves performance of growing (3.5%) and finishing (2.7%) pigs Under stress/disease conditions, acids appear to be effective in reducing scouring rate, mortality, and help maintain growth performance Response to acids is not remarkably influenced by type of diet, inclusion level of acid, weaning age or performance level or their interactions More studies are needed to assess the response of pigs to dietary protected acidifiers (i.e., organic acid blends, protection technologies)
Protected vs Unprotected OA
With unprotected organic acids Palatability issues Demineralization of bones Damage of stomach and intestinal mucus membrane Promotes bacterial resistance to acids With protected organic acids Supplies OA to small intestine in non-dissociated form allowing slow-release of active ingredients Helps to maintain optimal pH in (stomach) Decrease pathogenic and increase commensal bacterial populations Upadhaya et al. Asian-Australas J Anim Sci. 2014 Nov; 27(11): 1600–1607 Devi et al. R. Bras. Zootec. vol.45 no.2 Viçosa Feb. 2016
Meta-analysis publication bias
As with most reviews and meta-analyses, only peerreviewed published data utilized Depend on the quality of the data set available for analysis Tendency for scientists/journals to decline to publish results that fail to show significant differences Results in unquantifiable bias and overestimation of the value of some technologies Tung and Pettigrew, 2006
How and when are feed additives justified economically?
Consistency of response Response criteria? Response measureable? Interactions with other feed additives Cost vs risk of response Projected ROI – what is enough to justify use given all of the factors involved Meta-analysis publication bias?
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 Poor gut health contributes to economic challenges in animal production
Can we quantify (functional/descriptive) to further define “Healthy Gut” and pinpoint specific targets for feed additives?
Areas of opportunity 
Translational Genomics For Improving Sow Reproductive Longevity
Effect of energy restriction on weaning weight 6.4
Weaning Weight, kg
6.2 6
5.8 Control Restricted
5.6 5.4
P < 0.05
5.2 5 Parity 1
Parity 2
Postulated effects of human milk oligosaccharides Pediatric Research (2008) 64, 8â&#x20AC;&#x201C;10
Areas of opportunity
Development of a cecum-cannulated gnotobiotic pig model to evaluate gut microbial community dynamics and function at the molecular and physiological levels Evaluate defined microbial population 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
Questions