Prebiotic Feed Additives: Rationale and Use in Pigs
By John A. Patterson and presented at the 2005 Banff Pork - Disease has always been a critical issue in pig production, affecting not only animal health and well-being, but also the physical and economic health of the producer.
16 January 2006
8 minute read
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Thus, there is increasing interest in alternatives to growth promotant antibiotics. Fundamental to developing alternatives to growth promotant antibiotics is the enhancement of our understanding of defence systems used to inhibit pathogens, their interactions and regulation.
Host Defenses Against Infection
The pig’s defence against pathogens includes a combination of physical processes (gastric acidification, rapid transit through the small intestine), as well as the epithelial lining of the intestine, the mucosal immune system and the intestinal microbiota (Gaskins, et al., 2000, Mackie, et al., 1999). Effective defence against pathogens requires that all of these systems are functioning properly. Factors affecting these systems include genetics, pathogen load and stressors. We are just starting to learn about the extensive amount of cross talk between these systems (Deplancke and Gaskins, 2001, Hooper, et al., 2002, McCracken and Lorenz, 2001, Sonnenburg, et al., 2004, Xu and Gordon, 2003).
Symbiotic Microbiota
The microorganisms that are frequently associated with the majority of animals
are called by a variety of names (normal, commensal, indigenous, symbiotic)
and symbiotic will be used here. Opportunistic pathogens may be a small
component of this microbiota, but only become pathogenic in response to
specific environmental conditions. Studies using germ-free, gnotobiotic
(colonized by selected bacterial species) and conventional animals clearly
show that the symbiotic bacteria provide protection against enteric pathogens.
Although the intestinal microbiota is complex and the role of most of the
bacteria in protecting the pig is not clear, bacterial species of the genera
Lactobacillus and Bifidobacterium have been shown to provide protection
against enteric infections. These two genera have also been shown to be
suppressed when animals or humans are stressed. Recent research is
unfolding a picture of how the symbiotic bacteria inhibit enteric pathogens and
how they synergistically interact with the intestinal epithelium and mucosal
immune system.
The intestinal tract is sterile at birth and undergoes a succession of bacterial
populations before a stable microbial ecology is established. Facultative
organisms, such as E. coli, initially colonize the intestinal tract. As the animal
ages, the intestinal tract is subsequently colonized by relatively aerotolerant
lactic acid bacteria (lactobacilli and bifidobacteria), bacteroides and other
anaerobic bacteria (Mackie, et al., 1999, Tannock, 1997). The intestinal
microbial community structure becomes increasingly complex after weaning
and with time, the microbial community structure becomes relatively stable at
the genus level. However, there is increasing evidence that the species
composition within a genus is dynamic and varies between individual animals.
Thus, subtle changes in bacterial species may alter host resistance to
pathogens. The microbial community structure is thought to be altered when
the animal is stressed and this altered microbiota, along with altered epithelial
and immune function, provide pathogens with an increased opportunity for
colonization. Although the mechanisms of this decrease in bacterial resistance
and specific microbial population changes involved are not known, lactobacilli
and bifidobacterial populations have been shown to decrease in humans and
these or similar beneficial populations may be decreased in pigs.
The symbiotic intestinal microbiota inhibit pathogens through a variety of
mechanisms. The mechanism, or combination of mechanisms used depends
upon the microbial species and the ecosystem within which they are residing.
Possible mechanisms are:
- competition for nutrients
- production of toxic conditions or compounds (low pH, fermentation acids, bacteriocins, etc.)
- competition for binding sites on epithelial surfaces, or in the tightly adherent mucus layer
- stimulation of the immune system
The intestinal microbiota are in highest numbers in the lumen of the intestinal
tract, where competition for nutrients and production of toxic compounds would
logically be important. The intestinal microbiota also colonize the mucus layer
lining epithelial cells and thus competition for binding sites, in addition to
competition for nutrients and production of toxic compounds may be important.
It is also most likely that the mucosally associated microorganisms are directly,
or indirectly responsible for stimulating the immune system. Thus, manipulation
of the microbiota in specific ecosystems influences the efficacy with which the
symbiotic microbiota inhibits pathogens.
The symbiotic intestinal bacteria do not act alone to inhibit enteric pathogens,
but act in concert with the intestinal epithelial barrier and the mucosal immune
system. There are a number of management approaches that either enhance
or suppress this alliance. However, understanding how they function is
important in developing approaches to influence these defence systems.
Epithelial Tissues
The epithelial lining provides a physical barrier against entry of large molecules
and microorganisms into the body proper. The morphology of the epithelial
lining changes along the intestinal tract, but essentially consists of crypt regions
(where cells are generated from stem cells) and apical or villi (depending upon
location) regions, where cells have differentiated to perform different functions,
and eventually die and are released into the lumen of the intestine. Cell
turnover is rapid along the intestinal tract with cells being replaced every 3-5
days. Changes in epithelial tissue morphology alter nutrient absorption and
defence against pathogen invasions.
Although it is well known that pathogens
that attach to epithelial cells conscript the regulatory control of that cell, new
information indicates that at least some species of the symbiotic microbiota that
are in close association with the epithelium also influence activities of epithelial
cells (Hooper, et al, 2002, Xu and Gordon, 2003). These changes in epithelial
cell metabolism enhance colonization by those bacterial species and potentially
enhance protection of the epithelial surface from colonization by pathogens.
Thus, it is becoming increasingly clear that there is extensive cross-talk
between the intestinal microbiota and epithelial cells.
Mucosal Immune System
The mucosal immune system is comprised of lymph nodes (mesenteric lymph
nodes and Peyer’s Patches, located in the ileum) and diffuse lymphoid cells.
The immune system has both innate and adaptive arms (Pickard et al., 2004).
The innate system includes cells (macrophages, dendritic cells) that mount a
non-specific response to the presence of any foreign antigen. The adaptive
system has memory and once exposed to a pathogen, the adaptive system
produces antibodies that are protective against subsequent infections by the
same organism. Since the intestinal tract is constantly exposed to bacteria, it
has to develop tolerance to the symbiotic bacteria and does so through a
complex process.
The mucosal immune system develops tolerance to the
indigenous microbiota and food antigens, resulting in an accumulation of IgA
secreting B cells, T cells, macrophages and dendritic cells in the tissues lining
the intestinal tract. In essence, the mucosal epithelium elicits a mild or
controlled (Th1) inflammatory response to the symbiotic microbiota and a much
more dramatic inflammatory response to pathogens. This allows the mucosal
epithelium to respond more rapidly to pathogen challenge; however, it is
expensive, from an energetic standpoint, to maintain this primed immune
system in the absence of pathogen challenge (Anderson, et al. 2000). Good
management practices can minimize pathogen load.
Neuroendocrine
The mucosal epithelium is heavily innervated, with sympathetic and
parasympathetic nerves influencing normal function of the intestinal system and
mucosal tissues are exposed to hormonal action. When the animal is stressed,
the hypothalamic-pituitary axis (HPA) responds by secretion of corticosteroids
and direct neuronal stimulation of the mucosal tissues (Matteri, et al., 2000,
Petrovsky, 2001). Thus, stress associated with production, including
environmental, nutritional, weaning, transportation, and commingling suppress
the pig’s ability to resist pathogens and increases the incidence of subclinical or
clinical infection. Growth of some pathogenic bacteria is stimulated by addition
of the stress hormones norepinephrine and epinephrine. This has been shown
by growth in serum simulating medium and by increases in gram negative (E.
coli) bacteria in the intestinal tracts of animals stimulated to release
norepinephrine (Lyte, 2004). More information is needed on the interactions
between the neuroendocrine response to stressors and regulation of
pathogenic and symbiotic microbiota in the intestine.
Thus, there is extensive cross-talk between the various defence systems.
These systems are effective in suppressing pathogens, and under normal
conditions, few pigs become sick. Pigs that do become sick effectively control
the infection. However, when the pig is challenged by environmental conditions
that suppress one or all of these systems and when the pathogen load is high,
then it becomes much more likely that an individual pig will become infected,
the pig will become sicker and contribute to the pathogen load of pen mates
and results in spread of the disease.
Further Information
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Source: Paper presented during the 2005 Banff Pork Seminar Procedings
