CLOSTAT™ for poultry:

More than a health insurance,

better uniformity,
growth and survivability

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 CLOSTAT™: ensuring intestinal health
Through intestinal microbiome management

For animal health and production professionals ​who want to produce livestock sustainably, while
maintaining intestinal health, uniformity and performance, CLOSTAT™ is a proprietary probiotic
(Bacillus sp. PB6, ATCC PTA-6737) originating from natural enteritis resistant chickens, available for in
feed and on-farm use, that strongly supports animal production under antibiotic reduction conditions,
and other challenges such as environmental, legal or economical.

Benefits

• Reduces the need to treat with antibiotics

• Reduces the use of antibiotic growth promoters
• Tackles dysbiosis, wet litter and diarrhea problems
• Improves eggshell quality and discoloration
• Increases growth and uniformity
• Better survivability

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 What is CLOSTAT™?
Key features

Spores of Bacillus sp. ATCC PTA-6737 (PB6)

Originates from the intestine of healthy chickens

Several modes of action are scientifically proven

The spores are resistant to normal pelleting (85° C) or higher temperatures and low pH

Worldwide successful proven in broilers, layers, turkey, pigs and calves

Numerous scientific and commercial trials prove the modes of action and the performance improvements

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 CLOSTAT™: ensuring poultry intestinal health
Enteritis
Wet litter Benchmarking trial

Antibiotic reduction
Intestinal health… AGP replacement Overcoming
Heat stress challenges Microbiome

E. cecorum

Meat quality

Performance
Broiler breeders Meat
Parent stocks How it works Uniformity
Layer breeders
Production
Turkeys

Meat yield

…and performance Egg

Production

Young layers
Old layers
© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 CLOSTAT™: mode of action

How it works

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 CLOSTAT™: how it works
Overview of key modes of action

Bacillus sp. ATCC PTA-6737 (PB6):

1. Has the ability to produce of antibacterial metabolites

2. Produces quorum quenching molecules

3. Supports the growth beneficial bacteria in the intestine

4. Improves microbial diversity

5. Has anti-inflammatory effects to support the digestive tract during challenges

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 1. CLOSTAT™: Production of antibacterial metabolites
In vitro surfactin production of PB6

Normal bacteria of the chicken intestine, having antagonistic action against Clostridium perfringens

Production of lipopeptides: surfactins

Inhibition of PLA2

Lesions of the cell wall

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements. Kemin internal reference: PRE–10-00256
 1. CLOSTAT™: Production of antibacterial metabolites
Broad spectrum in vitro inhibition of different clostridial species

Clostridium perfringens

CLOSTAT™
CCM 7176

Clostridium perfringens
ATCC 13124

Kemin Internal Document WP-14-00076 Kemin Internal Document WP-08-00140 Clostridium perfringens
Kemin Internal Document WP-08-00140

NCTC 8798
Clostridium perfringens Clostridium septicum Clostridium difficile

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements.
 CLOSTAT™: key mode of action
Bacillus sp. PB6 produces fengycin, a quorum quenching molecule
Figure: Reduced pathogenicity by quorum quenching
1. Quorum sensing is required for Clostridium 2. Fengycin reduces pathogenicity by inhibiting quorum
pathogenicity and activates at high cell density sensing signal and messenger

Quorum sensing induces

Production of toxins No production of toxins
necrotic enteritis
Induction of enteritis
Enteritis not induced

C. Perfringens cells cannot

talk to each other, which
Pathogenic density prevents necrotic enteritis
of C. perfringens

Fengycin inhibits quorum

sensing

Fengycin

Pathogenic C. perfringens Bacillus sp. PB6

Quorum sensing messenger (AIP) Commensal clostridium spp

Quorum sensing receptor Quorum sensing inhibition

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements. Kemin internal reference: TPAS-20-1551
 3. CLOSTAT™: Stimulates beneficial bacteria
Research trial in old layers from 64 – 73 weeks

Table: Bacterial counts in the caca of laying hens given different dosages of CLOSTAT™

CLOSTAT™ CLOSTAT™
Bacteria Control
0.5 kg/ ton 1 kg/ ton
Lactobacillus 7.26 a 8.86 b 9.31 c

Bifidobacteria 8.08 a 9.16 b 9.74 c

Clostridium 9.25 a 8.80 b 8.20 c

Coliforms 9.03 a 8.43 b 8.12 c

Data with different letters are statistical significant with a P-value < 0.05

CLOSTAT™ supports the intestinal microbiota by:

• Improving the population of beneficial bacterial such as Lactobacillus and Bifidobacteria

• Controlling the populations of potentially pathogenic bacteria Clostridium spp

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements. Trop Anim Health Prod (2013) 45:1017–1024
 4. CLOSTAT™: Improves of microbial diversity
Effects of PB6 across the microbiome

Class
120
Proteobacteria Betaproteobacteria
Firmicutes Bacilli
100
Firmicutes Negativicutes
Bacteroidetes/Chlorobi group BCF group
80 CLOSTAT™
Bacteroidetes Bacteroidia
unclassified unclassified
increases
60
Proteobacteria Gammaproteobacteria the diversity
40
Firmicutes unclassified by 15%
Firmicutes Clostridia
Firmicutes Erysipelotrichia
20
Cyanobacteria Melainabacteria
Bacteroidetes unclassified
0
CLOSTAT CONTROL

© Kemin Industries, Inc. and its group of companies 2023. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A. Certain statements, product labeling and claims may differ by geography or as required by government requirements. Kemin internal reference: TD–16-00079