July | August

Feature heading: Anti-inflammatory

Feature title: Anti-inflammatory approach of Big FishTM on the growth of rainbow trout
International Aquafeed is published five times a year by Perendale Publishers Ltd of the United Kingdom.
All data is published in good faith, based on information received, and while every care is taken to prevent inaccuracies,
the publishers accept no liability for any errors or omissions or for the consequences of action taken on the basis of
information published.
©Copyright 2009 Perendale Publishers Ltd. All rights reserved. No part of this publication may be reproduced in any form
or by any means without prior permission of the copyright owner. Printed by Perendale Publishers Ltd. ISSN: 1464-0058

www.aquafeed.co.uk
 Anti-inflammatory
Anti-inflammatory approach
of Big Fish™ on the growth of
rainbow trout
by Mingder Yang, PhD of Aova Technologies, Inc. Madison, Wisconsin, USA and Mark E. Cook PhD University of
Wisconsin-Madison, Madison, Wisconsin, USA
T
he growth potential of
animals in modern agricul-
tural practices is five to
10 percent below genetic
potential.
This is evidenced by the work of Levs
and Forbes (1959), who showed that ani-
mals reared in a germ free environment,
grew 12 percent faster than those raised in
conventional environments.
In the late 1950s, animal research
revealed that the lost growth potential of
animals in consolidated environments could
be partially overcome by feeding antibiotics.
"Since intact antibody molecules cannot
cross the gut lining, the product acts
locally in the digestive tract by decreasing
gut inflammation"
By the mid 1970s, essentially all swine
and poultry raised for meat production
were fed antibiotics to stimulate growth
and improve feed efficiency.
However, since the mid-1980s there has
36 | InternatIonal AquAFeed | July-august 09
been growing concern that the use of anti-
microbials is generating antibiotic resistant
human pathogens in animal products.
In an article by Witte (1998) the fol-
lowing comment was made: “Industrial
investment in alternatives to antimicrobials
for animal growth promotion should…
[protect] the fragile resources that are
critical to successful management of human
infectious disease.”
The mechanism by which microbes
in the absence of overt disease, sup-
press the growth of farm animals has
begun to be elucidated. The interface
of microbes and animals results in the
constant need of the animal’s immune
system to maintain a vigilant defence
against a potential invasion. The animal’s
defence mechanism is not without cost.
The primary cost of this defence machin-
Anti-inflammatory
the kidney (Lupus), the joints (arthritis), that while animal performance can be Immune defence
the gastrointestinal tract (inflammatory improved by targeting unwarranted The major recruiter of immune defence
bowel disease), and even the skin (atopic inflammation, there are also indica- mechanisms in the animal is the eicosanoids.
dermatitis). In some diseases, as those in tions that resistance to infectious or These are lipids inflammatory mediators
humans mentioned above, the cellular and opportunistic pathogens is also reduced. that originate from membrane phospholip-
chemical machinery of the immune system Damage caused to the host due to ids (particularly arachidonic acid (AA) in the
begin to attack the body itself (autoimmune unwarranted inflammation may actually sn-2 position of phospholipids).
diseases).
Table 1:
First sign of inflammation Rearing Big Fish Weight gain Feed Efficiency # of Fish
In animal agriculture, the first sign of Trial Location Length
system dosage improvement improvement per tank
inflammation is evidenced by decreased ani-
mal performance as evidenced in decreased
growth and feed efficiency (Klasing, 1987). 1 Japan 1 mo flow through 0.30 % 7.6 % 17.3 % 15
Reduced performance can be observed 2 US 9 mo re-circulation 0.40 % 7.0 % n/a 200
in the absence of overt signs of inflamma-
3 US 2 mo flow through 0.30 % 27.8 % 8.1 % 12
tion. Decreased growth and feed efficiency
associated with unsanitary environments is 4 Portugal 6 weeks flow through 0.60 % 9.1 % 5.6 % 20
the result of unwarranted, yet sub-clinical
inflammation (Dafwang, 1987; Roura, 1992).
Restoring animal growth caused by provide an entryway for pathogens to During an immune stimulation, for
ery is reduced growth and poorer feed
unwarranted inflammation is the reasoning cause infection. example, simple presence of the nor-
efficiency (Cook, 2000).
behind the novel products developed by Hence it is not surprising that a manage- mal microflora of the animal, AA is
During every potential breach of the
Aova Technologies. ment program against inflammation is a man- released from the inner leaflet of the cell
animal’s defence against microbial invasion,
Results shown to date suggest agement program for better animal health. membrane via cytosolic PLA2 (cPLA2).
immune cells release hormones, known as
cytokines, which stimulate and recruit cells
involved in the defence of invading microbes.
Upon release of these cytokines - most
notably, interleukin-1 (IL-1) and tumor
necrosis factor (TNF) - the activation and
proliferation of white blood cells demand a
supply of nutrients for immune defence. It is
now well recognised that a primary source
of these nutrients for immune defences
is skeletal muscle via degradation, hence
decreased growth or weight loss.
This is exacerbated because skeletal mus-
cle catabolism greatly exceeds the nutrient
needs of the immune system (Cook, 2000).
Why Does Big Fish Work?
Inflammatory Responses on
Growth and Feed Efficiency
Inflammation is an important first
defence against infectious diseases; however,
unchecked - and more specifically, unwar-
ranted - inflammation typically creates
more damage to the host than could ever
be assigned to the original pathogen itself.
When inflammatory processes respond
to a perceived threat when none is truly
present, or to such a degree that the host’s
health is adversely impaired, the inflamma-
tion is considered unwarranted.
Diseases of unwarranted inflammation
can involve the airway (asthma and allergy),
July-august 09 | InternatIonal AquAFeed | 37
 Anti-inflammatory
The released AA is then acted on by
a number enzymatic systems, such as
the lipoxygenases to form leukotrienes
and the cyclooxygenases which form
prostaglandins.
These in turn cause a host of signalling
effects down stream including the recruit-
ment of inflammatory processes, and signal
transduction pathways that lead to inflam-
matory cytokine production.
In modern animal agricultural condi-
tions, in the absence of disease, this
response is severe enough to result in
decreased performance.
"Big Fish was able to help fish
realize the genetic potential in
growth and feed efficiency"
Indeed, trials recently run in Thailand
showed very significant improvements in
growth, feed efficiency and survivability.
Specifically, in grouper and Vietnamese
catfish trials, fish gained 15 to 20 percent
more body weight and improved feed effi-
ciency 26 to 47 percent over the 13 weeks
trial period. During the hot summer trialling
period, survivability was enhanced 82 and
46 percent respectively.
Furthermore, in a Streptococcus-challenged
tilapia trial, fish fed Big Fish supplement diet
survived 2.9:1 over control fed tilapia.
Fish trials
Several rainbow trout trials were con-
ducted to evaluate the benefit of Big Fish.
38 | InternatIonal AquAFeed | July-august 09
The trials, which were run by a feed com-
pany in Japan, are summarized in table 1.
Fish were grown from about 40 grams to
70 grams in the one-month trial.There was no
mortality and Big Fish improved weight gain by
7.6 percent and feed efficiency by 17.3 percent
in when compared to the control group.
Trial 2 was conducted in a government
aquaculture research facility. The fish were
started at about 20 grams and grown to
market size (~425 grams).
Trial 3 was a two-month trial run at a
university research facility. Rainbow trout
were grown from 20 to 70 grams. Big Fish
fed rainbow trout
had a 27.8 percent
growth improve-
ment and 8.1 per-
cent feed efficiency
over the control
group (Barry & Yang,
2008).
Trial 4 was a
six-week trial con-
ducted in a research
university in
Portugal. Rainbow
trout fed Big Fish,
grew 9.1 percent heavier and had 5.6
percent improvement in feed efficiency.
Realising genetic potential
Since Big Fish product from Aova
Technologies is designed to mitigate gut
inflammation, questions had been raised on
the safety of the product.
Specifically, could the product weaken the
animals’ immune system to fight diseases?
Data collected from numerous animal
studies showed no signs of abnormal mor-
tality or morbidity.
On the other hand, several reports showed
improved health and growth benefit especially
in sub-optimal environments or under specific
disease challenge (Scanes 2008).
Since intact antibody molecules can-
not cross the gut lining, and the active
ingredient in Aova Technologies’s anti-
PLA2 is avian antibody, the product does
not affect the systemic immune system.
Instead, the product acts locally in the
digestive tract by decreasing gut inflam-
mation. Big Fish was able to help fish
realize the genetic potential in growth
and feed efficiency.
References
Barry, T., Yang, M. (2008) Effects of anti-
phospholipase A2 on the growth of rainbow
trout. N. Amer. J. of Aquaculture. 70:236-239.
Cook, M.E., 2000. The interplay between
modern management practices and the chicken:
how immune response and the physiological
mechanism for growth and feed efficiency have
adapted over time. Where do we go from here?
In: Biotechnology in the Animal Feed Industry
(eds., T.P. Lyons and K.A. Jacques). Nottingham
University Press, pp 97-110.
Dafwang, I.I., M.E. Cook, and M.L. Sunde, 1987.
Interaction of dietary antibiotic supplementation
and stocking density on broiler chick performance
and immune response. Brit. Poultry Sci. 28:47-55.
Klasing, K.C., D.E. Laurin, P.K. Peng and D.M.
Fry. 1987. Immunologically mediated growth
depression in chicks: Influence of feed intake,
corticosterone and interleukin-1. J. of Nutr.
117:1629-1637.
Levs, M., M. Forbes. 1959. Growth response to
dietary penicillin of germ-free with a defined
intestinal flora. Brit. J. Nutr. 13:78-84.
Roura, E., J. Homedes and K. C. Klasing. 1992.
Prevention of immunologic stress contributes to
the growth-permitting ability of dietary antibiotics
in chicks. J. Nutr. 122:2383-2390.
Scanes, C.G., S.A. Cutler, R.W. Griffith, M. Yang
and M.E. Cook. 2008. Effects of egg antibody
to components of inflammatory activation
(phospholipase a2 and Toll like receptor 4) on
the response of young turkeys to Salmonella
typhimurium challenge. Avian Biol. Res. 1:167-175.
Witte, W. 1998. Medical Consequences of
antibiotic use in agriculture. Science 279:996-997.
for More inforMation:
Aova Technologies, Inc
Madison, Wisconsin,
USA
Tel: +1 608 3109595
Fax: +1 608 3109596
Website: www.aovatech.com