RECENT ADVANCES IN ANIMAL NUTRITION
CONTENTS 1 NUTRITION AND METABOLISM: FOUNDATIONS FOR ANIMAL GROWTH, DEVELOPMENT, REPRODUCTION, AND HEALTH 1 2 INSIGHTS INTO THE REGULATION OF IMPLANTATION AND PLACENTATION IN HUMANS, RODENTS, SHEEP, AND PIGS 25 3 A ROLE FOR FRUCTOSE METABOLISM IN DEVELOPMENT OF SHEEP AND PIG CONCEPTUSES 49 4 NUTRITIONAL REGULATION OF EMBRYONIC SURVIVAL, GROWTH, AND DEVELOPMENT 63 5 PHOSPHATE, CALCIUM, AND VITAMIN D: KEY REGULATORS OF FETAL AND PLACENTAL DEVELOPMENT IN MAMMALS 77 6 NUTRITIONAL AND PHYSIOLOGICAL REGULATION OF WATER TRANSPORT IN THE CONCEPTUS 109 7 AMINO ACIDS IN MICROBIAL METABOLISM AND FUNCTION 127 8 POTENTIAL REPLACEMENTS FOR ANTIBIOTIC GROWTH PROMOTERS IN POULTRY: INTERACTIONS AT THE GUT LEVEL AND THEIR IMPACT ON HOST IMMUNITY 145 9 MICROBIOMES IN THE INTESTINE OF DEVELOPING PIGS: IMPLICATIONS FOR NUTRITION AND HEALTH 161 10 L-ARGININE NUTRITION AND METABOLISM IN RUMINANTS 177 11 HEPATIC GLUCOSE METABOLISM AND ITS DISORDERS IN FISH 207 12 PROTEIN-SOURCED FEEDSTUFFS FOR AQUATIC ANIMALS IN NUTRITION RESEARCH AND AQUACULTURE 237 13 FUNCTIONAL MOLECULES OF INTESTINAL MUCOSAL PRODUCTS AND PEPTONES IN ANIMAL NUTRITION AND HEALTH 263 14 USE OF GENOME EDITING TECHNIQUES TO PRODUCE TRANSGENIC FARM ANIMALS 279 15 COWS AS BIOREACTORS FOR THE PRODUCTION OF NUTRITIONALLY AND BIOMEDICALLY SIGNI?CANT PROTEINS 299 16 USE OF AGRICULTURALLY IMPORTANT ANIMALS AS MODELS IN BIOMEDICAL RESEARCH 315 17 PIGS (SUS SCROFA) IN BIOMEDICAL RESEARCH 335 1 NUTRITION AND METABOLISM: FOUNDATIONS FOR ANIMAL GROWTH, DEVELOPMENT, REPRODUCTION, AND HEALTH ABSTRACT CONSUMPTION OF HIGH-QUALITY ANIMAL PROTEIN PLAYS AN IMPORTANT ROLE IN IMPROVING HUMAN NUTRITION, GROWTH, DEVELOPMENT, AND HEALTH WITH AN EXPONENTIAL GROWTH OF THE GLOBAL POPULATION, DEMANDSFORANIMAL-SOURCEDPROTEINAREEXPECTED TO INCREASE BY 60% BETWEEN 2021 AND 2050 IN ADDITION TO THE PRODUCTION OF FOOD PROTEIN AND ?BER (WOOL), ANIMALS ARE USEFUL MODELS FOR BIOMEDICAL RESEARCH TO PREVENT AND TREAT HUMAN DISEASES AND SERVE AS BIOREACTORS TO PRODUCE THERAPEUTIC PROTEINS FOR A HIGH EF?CIENCY TO TRANSFORM LOW-QUALITY FEEDSTUFFS AND FORAGES INTO HIGH-QUALITY PROTEIN AND HIGHLY BIOAVAILABLE ESSENTIAL MINERALS IN DIETS OF HUMANS, FARM ANIMALS HAVE DIETARY REQUIREMENTS FOR ENERGY, AMINO ACIDS, LIPIDS, CARBOHYDRATES, MINERALS, VITAMINS, AND WATER IN THEIR LIFE CYCLES ALL NUTRIENTS INTERACT WITH EACH OTHER TO IN?UENCE THE GROWTH, DEVELOPMENT, AND HEALTH OF MAMMALS, BIRDS, ?SH, AND CRUSTACEANS, AND ADEQUATE NUTRI- TION IS CRUCIAL FOR PREVENTING AND TREATING THEIR METABOLIC DISORDERS (INCLUDING METABOLIC DIS- EASES) AND INFECTIOUS DISEASES AT THE ORGAN LEVEL, THE SMALL INTESTINE IS NOT ONLY THE TERMINAL SITE FOR NUTRIENTDIGESTIONAND ABSORPTION,BUT ALSO INTIMATELY INTERACTS WITH A DIVERSE COMMUNITY OF INTESTINAL ANTIGENS AND BACTERIA TO IN?UENCE GUT AND WHOLE-BODY HEALTH UNDERSTANDING THE SPECIES AND METABOLISM OF INTESTINAL MICROBES, AS WELL AS THEIR INTERACTIONS WITH THE INTESTINAL IMMUNE SYSTEMS AND THE HOST INTESTINAL EPITHE- LIUM CAN HELP TO MITIGATE ANTIMICROBIAL RESIS- TANCE AND DEVELOP PREBIOTIC AND PROBIOTIC ALTERNATIVES TO IN-FEED ANTIBIOTICS IN ANIMAL PRO- DUCTION AS ABUNDANT SOURCES OF AMINO ACIDS, BIOACTIVE PEPTIDES, ENERGY, AND HIGHLY BIOAVAIL- ABLE MINERALS AND VITAMINS, ANIMAL BY-PRODUCT FEEDSTUFFS ARE EFFECTIVE FOR IMPROVING THE GROWTH, DEVELOPMENT,HEALTH,FEEDEF?CIENCY,ANDSURVIVAL OF LIVESTOCK AND POULTRY, AS WELL AS COMPANION AND AQUATIC ANIMALS THE NEW KNOWLEDGE COV- ERED IN THIS AND RELATED VOLUMES OF ADV EXP MED BIOL IS ESSENTIAL TO ENSURE SUF?CIENT PROVISION OF ANIMAL PROTEIN FOR HUMANS, WHILE HELPING REDUCE GREENHOUSE GAS EMISSIONS, MINIMIZE THE URINARY AND FECAL EXCRETION OF NITROGENOUS AND OTHER WASTES TO THE ENVIRONMENT, AND SUSTAIN ANIMAL AGRICULTURE (INCLUDING AQUACULTURE) KEYWORDS ANIMAL PROTEIN BIOMEDICINE HEALTH DISEASE INTESTINE DIET ABBREVIATIONS AAS AMINO ACIDS AEMB ADV EXP MED BIOL IUGR INTRAUTERINE GROWTH RESTRICTION 1 NRC NATIONAL RESEARCH COUNCIL SDEP SPRAY-DRIED EGG PRODUCT INTRODUCTION THERE ARE APPROXIMATELY 1032 MILLION ANIMAL SPECIES IN NATURE, WHICH INCLUDE MAMMALS, 4,000; BIRDS, 9,000; ?SH AND LOWER CHORDATES, 18,800; CRUSTACEANS, 45,000; REPTILES, 6,300; AMPHIBIANS, 4,200; AND INSECTS, 09 (WILSON 1992) AS IMPORTANT PARTS OF THE ECOSYSTEM, ANIMALS INGEST NUTRIENTS FOR SURVIVAL, GROWTH, DEVELOPMENT, REPRODUCTION, AND HEALTH DESPITE THEIR VAST DIVERSITIES AS TWO BROAD GROUPS (VER- TEBRATES AND INVERTEBRATES), ANIMALS EXHIBIT GREATER SIMILARITIES IN PHYSIOLOGY, METABOLISM, AND NUTRITION THAN DIFFERENCES (WU 2018) IN HUMAN CIVILIZATION, THERE HAS BEEN A RICH HISTORY OF STUDIES INVESTIGATING THE DIETARY REQUIREMENTS OF FARM (EG, LIVESTOCK, POULTRY, ?SH, SHRIMP, AND CRABS), COMPANION (EG, CATS, DOGS, AND HORSES), AND LABORATORY (EG, RATS AND MICE) ANIMALS FOR ENERGY, AMINO ACIDS (AAS), LIPIDS, VITAMINS, MINERALS, AND WATER DURING THEIR LIFE CYCLES UNDER VARIOUS PHYSIOLOGICAL AND PATHOLOGICAL CONDI- TIONS (BAKER 2008; BALDWIN 1995; BAUMAN ET AL 2011; BAZER ET AL 2011, 2015, 2018, 2021; BEITZ 1985; BERGEN 2007, 2021; BURRIN AND MERSMANN 2005; HALLORAN ET AL 2021; MATTHEWS ET AL 2016; NRC 2002; WEBB ET AL 1992; WU ET AL 2022; ZHANG ET AL 2015; ZHU ET AL 2022) THIS IS BECAUSE ANIMALS CONTRIBUTE TO (A) THE PRODUCTION OF HIGH-QUALITY FOODS (EG, MEATS, EGGS, AND MILK) FOR HUMAN CONSUMPTION, AS WELL AS RAW MATERIALS SUCH AS WOOL AND LEATHER FOR CLOTHING AND ACCESSORIES FOR HUMANS; (B) THE COMPANION- SHIP AND WELL-BEING OF HUMANS; (C) THE DEVELOP- MENT OF NEW BIOTECHNIQUES TO EF?CIENTLY PRODUCE PROTEINS AND OTHER BIOMOLECULES; AND (D) ADVANC- ING BIOMEDICAL RESEARCH TO PREVENT AND TREAT INBORN, METABOLIC, AND INFECTIOUS DISEASES OF HUMANS AND OTHER ANIMALS REVIEW ARTICLES OF SELECT TOPICS ON NUTRITION AND METABOLISM IN ANIMALS OF BOTH AGRICULTURAL AND BIOMEDICAL IMPORTANCE ARE HIGHLIGHTED IN THIS VOLUME OF ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY (AEMB) TO BENE?T OUR READERS (BERGEN 2022, DAI ET AL 2022; HAY ET AL 2022; JIA ET AL 2022; LI ET AL 2022; LI AND WU 2022; MONZANI ET AL 2022; MOSES ET AL 2022; MU ET AL 2022; REY- NOLDS ET AL 2022; SMITH AND GOVONI 2022; STENHOUSE ET AL 2022A, B; SWAGGERTY ET AL 2022; WU ET AL 2022; ZHU ET AL 2022) PRODUCTION OF HIGH-QUALITY FOOD PROTEIN AND FIBER (WOOL) BY ANIMAL AGRICULTURE FOR HUMAN CONSUMPTION, HEALTH AND WELL-BEING ANIMAL AGRICULTURE (INCLUDING AQUACULTURE) PLAYS AN IMPORTANT ROLE IN PROVIDING HIGH-QUALITY FOOD PROTEIN (EG, MILK, EGGS, AND MEAT) FOR HUMAN CONSUMPTION TO OPTIMIZE HUMAN GROWTH, DEVEL- OPMENT, HEALTH, AND WELL-BEING, ALTHOUGH A MIX OF COMPLEMENTARY PLANT PROTEINS THROUGH AN ADEQUATE UNDERSTANDING OF PROTEIN NUTRITION MAY ALSO RESULT IN A HEALTHY NUTRITIONAL STATE (GRILLEN- BERGER ET AL 2003; MURPHY AND ALLEN 2003; WU ET AL 2022) ANIMAL PROTEINS GENERALLY CONTAIN ADEQUATE AND BALANCED AMOUNTS OF ALL PROTEINO- GENIC (PROTEIN-CREATING) AAS FOR HUMAN CON- SUMPTION IN ADDITION, ANIMAL-SOURCED FOODS PROVIDE TAURINE, CARNOSINE (B-ALANYL-L-HISTIDINE), ANSERINE (B-ALANYL-L-1-METHYLHISTIDINE), AND CREATINE; THEY ARE NONPROTEINOGENIC NUTRIENTS THAT POSSESS ANTIOXIDATIVE PROPERTIES AND ARE CRUCIAL FOR ENERGY METABOLISM IN TISSUES, BUT ARE ABSENT FROM PLANT-SOURCED FOODS (WU 2020B) AS A PART OF HEALTHY DIETS FOR HUMANS, ANIMAL-SOURCED FOODS ALSO CONTAIN HIGHLY BIOAVAILABLE ESSENTIAL MINERALS (EG, IRON, ZINC, COPPER, MANGANESE, AND SELENIUM) AND VITAMINS (MURPHY AND ALLEN 2003) THIS IS IN CONTRAST TO A MYTH THAT THERE ARE VIRTUALLY NO NUTRIENTS IN ANIMAL-BASED FOODS THAT ARE NOT BETTER PROVIDED BY PLANTS FURTHERMORE, ANIMAL BY-PRODUCTS FROM THE RENDERING INDUSTRY ARE MAJOR SOURCES OF PROTEIN, AAS, BIOACTIVE RECENT ADVANCES IN ANIMAL NUTRITION - 2 PEPTIDES, LIPIDS, MINERALS, AND VITAMINS IN THE DIETS OF LIVESTOCK, POULTRY, ?SH, AND CRUS- TACEAN, AND IN PET FOODS (LI AND WU 2022; LI ET AL 2021E; WILKINSON AND MEEKER 2021) IMPROVED ANIMAL NUTRITION CAN ENHANCE THE QUALITY OF FOODS FOR HUMAN CONSUMPTION, WHEREAS HEALTHY COMPANION ANIMALS CONTRIBUTE TO THE WELL-BEING OF THEIR OWNERS FINALLY, WOOL (TEXTILE ?BER; CYSTEINE-RICH A-KERATIN PROTEINS) PRODUCED BY SHEEP AND OTHER ANIMALS (INCLUDING CASHMERE AND MOHAIR FROM GOATS) IS USED TO MANUFACTURE CLOTHS AND RELATED DAILY LIFE PRODUCTS (CAO ET AL 2021) PRODUCTION OF PROTEINS BY ANIMALS REQUIRES SUF?CIENT PROVISION AND OPTI- MUM UTILIZATION OF DIETARY AAS AND OTHER NUTRI- ENTS (BERGEN 2021; GILBREATH ET AL 2021; HE ET AL 2021A; LI ET AL 2021A, B; ZHANG ET AL 2021) THIS INDICATES A CLOSE LINK BETWEEN ANIMAL AND HUMAN NUTRITION ACCORDING TO THE FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS (FAO 2021), THE GLOBAL NUMBERS OF LIVESTOCK AND POULTRY HAVE INCREASED BY 36-FOLD OVER THE PAST 60 YEARS TO ABOUT 33 BILLION HEAD IN 2019 (TABLE 11) FUR- THERMORE, THE GLOBAL AQUACULTURE PRODUCTION HAS INCREASED OVER THE PAST DECADE AT AN AVERAGE RATE OF ABOUT 35% PER YEAR TO BE APPROXIMATELY BILLION KG IN 2019 AND PROVIDES MORE THAN 50% OF ?SH ?LETS FOR HUMAN CONSUMPTION (FAO 2020) BOTH EXTENSIVE (EG, GRAZING PASTURE) AND INTENSIVE (EG, INDOOR HOUSING) SYSTEMS ARE CUR- RENTLY USED TO RAISE RUMINANTS (EG, CATTLE, SHEEP, AND GOATS) AND NONRUMINANTS (EG, SWINE AND POULTRY) WORLDWIDE (BAZER ET AL 2020) AQUATIC ANIMALS ARE RAISED THROUGH BOTH THE OUTDOOR PONDS AND THE INDOOR RECIRCULATING AQUACULTURE SYSTEMS (EBELING AND TIMMONS 2012) FARM ANIMALS ARE BIOLOGICAL TRANSFORMERS THAT CONVERT TABLE 11 GLOBAL STOCKS OF LIVESTOCK SPECIES AND POULTRY IN 1961 AND 2019A SPECIES YEAR WORLD AFRICA AUSTRALIA BRAZIL CANADA CHINA EUROPE INDIA MEXICO USA CATTLE 1961 942 123 192 176 2019 1510 361 215 117 193 CHICKENS 1961 3906 274 132 541 1329 108 751 2019 25,915 2043 112 1467 171 5247 2020 808 581 1972 DUCKS 1961 193 100 2019 1,177 720 GEESE + GF 1961 – – – – – 2019 362 – – 312 – – – GOATS 1961 349 2019 1090 459 137 149 HORSES 1961 2019 PIGS 1961 406 168 2019 850 316 187 RABBITS + HARES 1961 – – – – 2019 300 – – 233 – – SHEEP 1961 994 135 153 267 2019 1240 408 163 128 TURKEYS 1961 204 – 108 2019 428 – 229 AADAPTED FROM FAO (2021) VALUES ARE 106 HEAD GF = GUINEA FOWL; USA = UNITED STATES OF AMERICA; “–” = DATA ARE NOT AVAILABLE RECENT ADVANCES IN ANIMAL NUTRITION - 3 MATERIALS NOT CONSUMED BY HUMANS (EG, FORAGES; BY-PRODUCTS OF PLANTS SUCH AS PASTURE GRASSES, ALFALFA, CLOVERS, HAYS, STRAW, AND SILAGES; AND RENDERED ANIMAL BY-PRODUCTS) INTO HIGH-QUALITY FOODS (WILKINSON AND MEEKER 2021; WU 2018) AS DOCUMENTED IN THIS VOLUME OF AEMB, RECENT RESEARCH ON DIETARY REQUIREMENTS FOR NUTRIENTS (PARTICULARLY AAS) IS EXPECTED TO ENHANCE THE EF?CIENCY OF ANIMAL AGRICULTURE GLOBALLY AND ALLEVIATE ITS POTENTIAL ADVERSE EFFECTS ON THE ENVIRONMENT THE SIGNI?CANCE OF ANIMAL AGRICULTURE IS INDICATED BY THE FACT THAT THIS ENTERPRISE ACCOUNTS FOR 50–75% AND 25–40% OF THE TOTAL AMOUNT OF AGRICULTURAL OUTPUT IN INDUS- TRIALIZED AND DEVELOPING COUNTRIES, RESPECTIVELY (WU ET AL 2014C) ANIMAL-SOURCED FOODS CAN PREVENT PROTEIN DE?CIENCY IN CHILDREN AND ADULTS (INCLUDING THE ELDERLY AND HOSPITALIZED PATIENTS) WORLDWIDE, PARTICULARLY THOSE LIVING IN UNDERDE- VELOPED NATIONS (WU 2021) IN 2016, ABOUT MILLION PEOPLE (107% OF THE WORLD POPULATION) HAD CHRONIC DE?CIENCIES OF NUTRIENTS, PARTICULARLY PROTEIN, VITAMINS, AND MICROMINERALS (FAO 2018), AND GLOBALLY 150 MILLION CHILDREN UNDER ?VE YEARS OF AGE WERE STUNTED IN THEIR GROWTH (UNICEF 2018) MATERNAL MALNUTRITION DURING GESTATIONAL AND NEONATAL PERIODS AFFECTS NOT ONLY THE ?RST GENERATION OF OFFSPRING, BUT ALSO SUBSE- QUENT GENERATIONS THROUGH EPIGENETIC-MEDIATED MECHANISMS (DEL CURTO ET AL 2013; WANG ET AL 2012) PREVENTING HUNGER AND MALNUTRITION WILL BE AN EVEN GREATER CHALLENGE AS THE GLOBAL POP- ULATION IS EXPECTED TO GROW EXPONENTIALLY FROM (UNITED NATIONS 2021) THE DEMANDS FOR ANIMAL- SOURCED PROTEIN ARE EXPECTED TO INCREASE BY 60% BETWEEN 2021 AND 2050 FOR SUPPORTING OPTIMAL HUMAN GROWTH AND MITIGATING SARCOPENIA IN THE ELDERLY THUS, ANIMAL AGRICULTURE PLAYS AN IMPORTANT ROLE IN PROVIDING ANIMAL-SOURCED FOOD AS PART OF A HEALTHY DIET FOR HUMANS, WHILE CON- TRIBUTING TO SCIENTI?C, ECONOMIC, AND SOCIAL DEVELOPMENTS WORLDWIDE ANIMALS AS MODELS FOR BIOMEDICAL RESEARCH AND AS BIOREACTORS FOR PRODUCING THERAPEUTIC PROTEINS BIOLOGICALLY, HUMANS ARE MEMBERS OF THE ANIMAL KINGDOM AS NOTED PREVIOUSLY, PIGS, SHEEP, CAT- TLE, CHICKENS, AND ?SH ARE AGRICULTURALLY IMPORTANT DOMESTIC ANIMAL SPECIES THERE IS GROWING INTEREST IN THEIR USE AS ANIMAL MODELS FOR NUTRITION RESEARCH WORLDWIDE THIS IS BECAUSE THE NATURE OF MEDICAL RESEARCH OFTEN INVOLVES INVASIVE TISSUE COLLECTIONS AND SURGICAL PROCEDURES AND MAY RESULT IN POTENTIAL HARMFUL EFFECTS (BERGEN 2021; GOVONI ET AL 2019; IRELAND ET AL 2008; JIA ET AL 2021; ODLE ET AL 2017; REYNOLD ET AL 2019, 2022; SMITH AND GOVONI 2022; WEBB ET AL 1992; WU AND KNABE 1994) THUS, IT IS NEITHER ETHICAL NOR PRACTICAL TO CONDUCT SUCH STUDIES WITH HUMANS IN THE FETAL, INFANT, OR ADULT STAGES OF LIFE SIMILARITIES, MAJOR DIFFERENCES, AS WELL AS ADVANTAGES AND DISADVANTAGES OF PORCINE, OVINE, BOVINE, AVIAN, AND ?SH MODELS ARE SUMMARIZED IN TABLE 12 EXAMPLES OF USING ANIMAL MODELS TO PURSUE NUTRITION RESEARCH ARE HIGHLIGHTED IN TABLE 13 OF PARTICULAR NOTE, RESULTS OF THOSE STUDIES HAVE AIDED IN DELINEATING THE MECHANISMS FOR THE FOLLOWING PHYSIOLOGICAL OR PATHOLOGICAL FEATURES IN HUMANS: (1) INTRAUTERINE GROWTH RESTRICTION (IUGR); (2) ARGININE DE?CIENCY AND HYPERAMMONEMIA IN PRETERM INFANTS; (3) ABUN- DANCE OF POLYAMINES AS WELL AS GLUTAMINE AND PROLINE IN MILK; (4) THE OBLIGATORY ROLE OF DIETARY AAS IN INTESTINAL INTEGRITY; (5) HYPERGLYCEMIA- INDUCED ENDOTHELIAL DYSFUNCTION; (6) AMMONIA TOXICITY IN PATIENTS WITH N-ACETYLGLUTAMATE DE?- CIENCY; (7) EXTRAHEPATIC UREA SYNTHESIS IN THE SMALL INTESTINE OF POST-WEANING MAMMALS; (8) THE SUSCEPTIBILITY OF NEONATES TO INTESTINAL DISEASE; AND (9) BIOMARKERS FOR INTESTINAL ADAPTATION IN PRETERM NEONATES (RHOADS ET AL 2005; RHOADS AND WU 2009; WU AND MORRIS 1998; WU ET AL RECENT ADVANCES IN ANIMAL NUTRITION -