DSM Gut Health School 15-16 March, 2018 Copenhagen
Use of biomarkers in relation to beneficial microbiota or their metabolites in the gastro- intestinal tract Pietro Celi (DVM, PhD) DSM Nutritional Products, Columbia (MD), USA
For Internal Use Only Outline • Introduction • Gastro-Intestinal (GAIN) Functionality – #feed4GAIN • GAIN biomarkers – Microbiota – Omics – VOCs • Conclusions Page 2
For Internal Use Only #feed4GAIN in Animal Nutrition and Health Provides resistance against entero- pathogens Optimizes feed Minimum foul conversion odor ratio Less wastage of nutrients Proper Checks digestion and mortality and absorption of morbidity valuable feed losses nutrients Page 3
For Internal Use Only Key aspects of GAIN functionality Immune response Gut-brain axis Nutrient uptake Immune tolerance Prevention of Energy homeostasis Malnutrition Feed allergens infections & behaviour GIT more than digestion and absorption Page 4
For Internal Use Only Key aspects of GAIN functionality PWD and Digestive digestive stress disorders Immune Environmental system stress compromised Page 5
For Internal Use Only Key aspects of GAIN functionality Necrotic Healthy Infections enteritis chicken Dietary factors Reduced immunit y Normal Undigested excreta feed Impaired GAIN functionality Page 6
For Internal Use Only GA stro- IN testinal (GAIN) Functionality Page 7 #feed4GAIN
For Internal Use Only GA stro- IN testinal (GAIN) Functionality Diet • ‘a steady state where the Immune Digestion & stat us absorption microbiome and the intestinal tract (host) exist Gastrointestinal in symbiotic equilibrium Functionality and where the welfare and GIT Welfare microbiota performance of the animal is not constrained by GIT mucosa intestinal dysfunction’ Page 8 #feed4GAIN
For Internal Use Only Gastrointestinal microbiota • Regulation of host homeostasis • Changes in feeding practices, imbalanced diet will impair GIT microbiota • Feed for GAIN (#feed4GAIN) • What are the factors that influence the development of the GIT microbiota? • What is the role of the GIT microbiota in the relationships between animal nutrition, GIT physiology, immune status and the gut -brain axis? Page 9 #feed4GAIN
For Internal Use Only Eubiosis vs disbiosis • Maximum performance of can only be achieved, if a balance of beneficial and non beneficial bacteria tract occurs. • Under conditions of stress, beneficial bacteria especially the lactobacilli have a tendency to decrease in numbers and be overgrown by the non-beneficial ones . • This situation can lead either in clinical signs or subclinical in a reduction of growth and feed efficiency . Page 10
For Internal Use Only Gastrointestinal microbiota as BFF Page 11
For Internal Use Only Feed efficiency and the GIT microbiota Genetics GIT Age Diet Microbiota Environment Page 12
For Internal Use Only Feed efficiency and the GIT microbiota Genetics Feed Age Diet Efficiency Environment Page 13
For Internal Use Only Gastrointestinal microbiota: the OMICS approach • Microbiota level (community of microbes): – List of discriminating species and families of bact eria, shift of population • Microbiome level (genes) – Link to metabolic and biochemical functions – Indicat ion on MoA of treatment • Faeces vs caecum vs ileal content • Analysis vs zootechnical parameters • Analysis vs biomarkers Page 14
For Internal Use Only Microbiota diet and age related changes Cecal microbial communities by diet Torok et al. (2011) AEM 77: 5868 http:/ / dx.doi.org/ 10.1093/ femsle/ fnv122 Page 15
For Internal Use Only Are variations in GIT microbiota responsible for differences in feed efficiency? Page 16 Torok et al. (2011) AEM 77: 5868
For Internal Use Only Microbiota development is crucial Distribution of FCR values given as a probability density function across the Multivariat e analysis PCA plot of cecal microbiota three trials. Trial 1 grey, trial 2 black, and trial 3 light grey. Page 17 S tanley et al. (2013) PloS ONE 8(12): e84290
For Internal Use Only Fecal microbiome of high and low FCR broilers Phylum Low FCR High FCR Actinobacteria 150 (0.979 % ) 71 (1.40 % ) Bacteroidetes 1088 (7.10 % ) 887 (17.53 % ) Firmicutes 1834 (11.97 % ) 1393 (27.53 % ) Fusobacteria 34 (0.222 % ) 8 (0.158 % ) Proteobacteria 12069 (78.83 % ) 2633 (52.04 % ) S pirochaetes 13 (0.084 % ) 2 (0.039 % ) S ynergistetes 43 (0.280 % ) 15 (0.296 % ) Verrucomicrobia 11 (0.071 % ) 5 (0.098 % ) – Unclassified 30 (0.195 % ) Other 37 (0.182 % ) 47 (0.929 % ) S ingh et al. (2014) J Appl Genet 55: 145 Page 18
For Internal Use Only Volatile Organic Compounds in piglets feces Page 19
For Internal Use Only Volatile Organic Compounds in piglets feces FS=0 FS=1 FS=2 Page 20
For Internal Use Only Volatile Organic Compounds in piglets feces Page 21
For Internal Use Only Volatile Organic Compounds in piglets feces ROC for intervention Top row (left to right), A vs B; A vs C; A vs D. A: LP - eubiotic B: LP + eubiotic C: HP - eubiotic D: HP + eubiotic Bottom row (left to right) B vs C; B vs D; C vs D. Page 22
For Internal Use Only Fate of proteins in the gut Aromatic AA Phenolic and (tryptophan) indolic compounds Proteins Ammonia Amino acids (AA) Other AA Amines H 2 , CO 2 , CH 4 , organic acids S ulfur AA S ulfur compounds (cysteine) Page 23
For Internal Use Only Fecal VOCs S hort Chain Hydrogen Branched-chain Ammonia Fatty Acids sulfide fatty acids (S CF As) Formic acid isobutyrate, 2- acetic acid methylbutyrate propionic acid isovalerate butyric acid valeric acid Page 24
For Internal Use Only Metabolites produced by microbial fermentation Page 25
For Internal Use Only Volatile Organic Compounds in piglets feces Page 26
For Internal Use Only Conclusions • Gastro-Intestinal Functionality is a key aspect for maintaining health, welfare and productivity • Optimal Gastro-Intestinal Functionality is crucial to promote sustainability of livestock and poultry farming • Modern technologies (microbiota profiling, genomics, metagenomics, metabolomics etc.) enable better understanding of key aspects of GAIN functionality and how to measure it • Modern technologies enhances the identification and selection of feed ingredients / feed additives ( Eubiotics ) which can effectively modulate gut microbiota and maintaining eubiosis in the gut Page 27 #feed4GAIN
For Internal Use Only Conclusions • Need to translate current knowledge into practical applications • GAIN Biomarkers are needed to – Assess of GAIN functionality – Evaluate nutritional interventions (#feed4GAIN) • We propose a multidisciplinary system- based approach where markers of each of the 6 key domains are integrated in a biomarker panel Page 28 #feed4GAIN
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