NUTRITIONAL SOLUTIONS

BEYOND AGPs

MUHAMMAD ATHAR
HI-TECH GROUP
 Growth promoter
• Administration of anabolic steroid hormones, use of growth
hormone (GH) or insulin-like growth factor (IGF-1) to
augment endogenous GH levels

Can we say Antibiotics “Growth Promoter”?

 Why feed AGPs?
Usually growth promotion action of AGPs is mediated by their
antibacterial effect
i. Nutrients may be protected against bacterial destruction;
ii. Absorption of nutrients may improve because of a thinning of
the small intestinal barrier;
iii. The antibiotics may decrease the production of toxins by
intestinal bacteria;
iv. There may be a reduction in the incidence of subclinical
intestinal infections.
» Better growth rate
» Better FCR
 History of Antibiotics
 1940’s: Identification of Growth enhancement properties
-Fermentation waste from tetracycline production was fed to
chickens as source of vitamin B12
 1950’s: widespread of antimicrobials as feed additives
without vet. prescription
 In the 1950’s and 1960’s, each European state approved its
own national regulations about the use of antibiotics in
animal feed
 Later on, till 1980’s different antibiotics were permitted to
use in animal feed on basis of criteria over national level
  In 1997, the drug resistant bacteria became clearer to
world?
 World Health Organization recognized danger of animal
antibiotic use
 Antimicrobial Growth Promoters (AGP)

• Antimicrobial substances used as a supplement in

animal feed in sub-therapeutic concentrations
Avoparcin (G+)
Spiramycin (G+)
Bacitracin (G+)
Avilamycin (G+)
Virginiamycin (G+)
Flavomycin (G+)
Kitasamycin (G+)
Enramycin (G+)
Carbadox (G-)
 Restrictions on use of Antibiotics
 Sweden was the first country to regulate the ban on use of
antibiotics growth promoters in farm animals in 1985
 In 1994, Denmark banned the antimicrobials in food
animal production
 The World Health Organization (1997) and the Economic
and Social Committee of the European Union (1998)
indicated that the use of antimicrobials in food animals is a
public health issue.
 However, concerns about development of antimicrobial
resistance and about transference of antibiotic resistance
genes from animal to human microbiota, led to withdraw
approval for antibiotics as growth promoters in the
European Union since January 1, 2006.
 The Politics
 Sweden banned Avoparcin in 1886 & Swedish model was
supported by other Scandinavian countries
 When Sweden & Finland entered EU in 1995 laws were permitted
that they could continue their ban of in-feed antimicrobials
 Where as European Scientific Committee on Animal Nutrition
(SCAN) up till 1996 did not recommend ban on antibiotic use.
 Avoparcin and vancomycin are glycopeptide antibiotics and
were linked with Vancomycin Resistant enterococci (VRE)
 The prevalence of VRE in EU before ban was much lower than USA,
in spite of the fact that Avoparcin has never been fed to food
animals in USA
 Interestingly in the last published Danish Antimicrobial Resistance
monitoring and Research Program (DANMAP) report (2010)
indicated 47% chicken isolates exhibited E.faecium resistance to
Vancomycin 15 years after the ban of Avoparcin
Molecular Mass of feed Antibiotics (g/mole)
Avoparcin 1747
Spiramycin 843
Avilamycin 1404
Bacitracin 1422
Bambermycin 1583
Virginamycin 1349
ENRAMYCIN 2355 (5-10 ppm)
Salinomycin 751 (anticoccidial)
Maduramycin 917
Norfloxacin 319 (to treat bacterial
infections)
Glucose 180
 Beyond AGPs
Zinc Oxide was 1st attempt to prevent enteric diseases
& resultantly increased concentrations of land with
Zinc, as Zn is poorly absorbed, it becomes highly
concentrated in manure, creating a risk of
environmental pollution.
In addition, it has other disadvantages as well, such as
a reduction in feed palatability
 Beyond AGPs
• Probiotics • Organic Acids
• Prebiotics • Bacteriophages
• Synbiotics • Lysozymes
• Phytobiotics • Enzymes
 Herbs  NSP
 Botanicals  Phytases
 Essential Oils  Proteases
 Oleoresins
 Probiotics
Probiotics are dietary supplements that contain live bacteria with or without
yeast

Probiotics increase the population of “good” bacteria which are needed in

the intestinal tract

They compete with pathogens for

–Receptors on the surface of intestinal epithelial cells
–Binding sites on mucus, extra cellular matrix , food particles or other sites in
the GI tract

 Improves Growth
 Feed Efficiency
 Intestinal Health
 Stimulates Immune Response
 Probiotics as Antimicrobials
Probiotics microorganisms produce antimicrobial substances
such as
1. Low molecular weight substances such as
 Organic Acids
 Alcohols, hydrogen peroxide
 Ammonia
 Lipoteichoic acid
 Siderophores
 Diacetyl
2. Bacteriocins which is thought to contribute to antimicrobial
activity of some probiotics
 Probiotics Immune Enhancement
• Probiotics can have simultaneously effects on both
antigen specific and non specific immune
functions
• Probiotics administration leads to
 Increasing macrophages numbers
 Increasing phagocytic activity
 Increasing production of cytokines which are involved
in modulation of both specific and non specific immune
responses
 Enhancing specific local and systemic IgA responses
 Selection of Probiotics
Genera proposed for use as probiotics in food animals
1. Bacteria
– Bacillus
– Lactobacillus
– Bifidobacterium
– Enterococcus
– Proteus
– Streptococcus
2.Fungi
– Saccharomyces
– Aspergillus
 Prebiotics
 Group of Nutrients that act as substrate for
probiotics & other gut microbiota to yield
SCFA
 Fructo-oligosaccharides / inulin (FOS)
 Glacto-oligisacchrides (GOS)
 Manno-oligosacchrides (MOS)
 Trans-glacto-oligosaccharide (TOS)
 Prebiotic Characteristics
• Resistant to acidic pH of stomach
• Can't be hydrolyzed by enzymes
• Shouldn't be absorbed in GI tract
• It can be fermented by intestinal microfloa
• Degree of polymerization (DP) equal or
higher than three as Inulin with fructose has
DP above 60 and DP of FOS is less than 10
 Synbiotics
Dietary supplements combining probiotics and
prebiotics in a form of synergism, hence symbiotic.

Synbiotic

Pro-Biotics Pre-Biotic
 Synbiotic
• True probiotic, without its prebiotic food,
does not survive well in the digestive system
• Combination of a pro-biotic and pre-biotic,
i.e. Synbiotics, might be more effective than
either a pro or pre biotic alone.
 ORGANIC ACIDS
• Following the ban of antibiotic growth promoters (AGPs) in
2006, the use of organic acids in animal nutrition has gained
significant importance in the feed industry

• Organic acids can be defined as carboxylic acids including fatty

acids, which have the chemical structure of R-COOH with acidic
properties

• Their positive effects on feed quality and animal performance

have been known for decades and, as they increasingly capture
the attention of the feed industry and more studies are going
on in this aspect
 Anti-Microbial action organic acid
• The undissociated form of the organic acid penetrates
the cell membrane of bacteria
• Inside the cell the acid dissociates according to
internal pH;
HCOOH -----(anion)+(proton)
• The H+ (proton) decrease pH in the cell
• The bacteria uses its energy to remove
the protons and dies
• Anions of organic acid deactivate NA
transferase enzyme, which damage nucleic acid
multiplication and results in death of the organism
 Other benefits of organic acids
• Reduction of gastric pH
• Reduction of buffering capacity of diets
• Stimulating the activity of digestive enzymes
• Increase of nutrient digestibility
• Promotion of beneficial bacterial growth
• Reduction of pathogens
• Direct killing of bacteria
• Depolarization of the bacterial membrane
 • Formic, Acetic, Propionic. Reduces
Short pH & affects directly gram-
bacteria
Chain Fatty • Fumeric, Citric, Malic, Lactic
• Indirect effect on the Bacterial
Acid Population by pH reduction, acting
mainly on stomach

Medium • Capric, Caprylic, Lauric acid

Chain Fatty • Direct & Strong antimicrobial effect
on Gram+ and Gram- bacteria
Acids
Role in Feed Role in Role in
Preservation Intestinal tract Metabolism

Improves
pH pH
nutriment
Reduction Reduction digestively

Improve
Antimicrobial Increase enzyme
Reaction Villi Length secretion

Reduction in Antimicrobia Stimulates

Bacteria Count l Action immunity

Improves Reduced bio-genic

pepsin amine production
activity
 Disadvantages Organic Acid
 Liquid
 Volatile
 A strong unpleasant odor
 not easy to store and transport
 Difficult to use directly in feed
 Phytogenic feed additives
 Derived from plants, herbs and spices are
used to improve animal performance.
– Positive effect on growth
– Improved immune system
– Reduced stress response
 Mode of action of phytogenic feed
additives
• Effect on gut morphology:
• On one side PFA irritate intestinal tissues
which have positively influenced the secretory
activity of trypsin and amylase. (Lee et
al.,2003)
• On the other side they change the microbial
population to a more favorable composition.
 Herbs
Botanicals
Phytobiotics
Classification Essential Oils

Oleoresins
 Bacteriophage
• Bacteriophage are viruses that infect and kill
bacteria.

• Bacteriophage control pathogens of

gastrointestinal tract
• Protect from E.coli and Salmonella infection in
chickens
• Limitations of bacteriophage are their specificity,
concerning regulatory acceptance, and practical
routes of administration.
 Lysozyme
• Lysozyme is a glycoside hydrolase that
catalyzes the hydrolysis of 1,4-beta-linkages
between N-acetylmuramic acid (NAM)and
N-acetyl-d-glucosaamine (NAG)residues in
peptidoglycan, which is major component
of gram positive bacteria and cell wall.
• Egg white
• Bacterial fermentation
 Challenges for Institutions
• Expertise in analytical techniques
– Microbiological inhibition
– High voltage electrophoresis
– Thin layer chromatography
– High performance liquid chromatography
– Liquid chromatography-Mass spectroscopy
• Availability and culture facilities for Clostridium
perfringens
• In vitro GI models for stomach, small intestine &
large intestine