Burkey interaction gut nutrition jefo2016

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) 

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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  

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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

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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

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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

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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

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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)

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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 

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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  

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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