Gut Permeability: the Relationship Between a Healthy Gut and a Healthy Pig

Dr Daniel Nelson, Technical Service Manager, Swine, for Alpharma Animal Health, explains why pigs consuming bacitracin perform more efficiently than their non-supplemented counterparts, especially during periods of stress. The paper was presented at Alpharma's Swine Enteric Health Symposium 2008.
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Dr Daniel Nelson


The gastrointestinal (GI) tract of the pig presents an extensive surface area providing direct contact between the pig and a large assortment of nutrients, microbes and exogenous toxins. The intestine should permit the exchange of nutrients between the gut lumen and the systemic circulation, while at the same time preventing penetration of pathogenic organisms and toxic compounds (Gaskins, 1997). The GI tract is the largest “organ” of the immune system. About 25% of intestinal mucosa is comprised of lymphoid tissue and more than 70% of all immune cells are found within the intestine (Gaskins, 1997).

The GI tract is also an energy “sink”. It has been estimated that due to its rapid turnover, the GI tract uses about 50% of the maintenance energy requirements of a pig. Normal cellular turnover (once every 3-6 days) minimizes the opportunity for colonization by pathogenic microbes.

However, disease and stress increase epithelial cell turnover rate. During a disease challenge or during periods of stress, more energy and nutrients are shunted to the intestine to replenish intestinal cells, slowing pig growth. Intestinal epithelial damage from disease insult and stress can also reduce absorption of nutrients and decrease enzyme activity, causing poorer feed conversion (F/G). Intestinal epithelial cell damage can also reduce intestinal barrier function, resulting in diarrhoea and increased risk of morbidity and mortality.

Heat Stress: Humans and Pigs

During the hot summer months, heat stress in humans is not uncommon. Light cases of heat stress are characterized by heat rash, sunburn, cramps in the arms, legs, and stomach, and possible fainting. Heat stroke in humans is characterized by a body temperature greater than 105.8°F. Heat stroke victims have dry skin, an elevated heart rate, and may act confused. Left untreated, heat stroke victims can have convulsions, lapse into unconsciousness, and die.

Although not documented in as much detail, it is well know that pigs experience heat stress during periods of high environmental temperatures. Performance often deteriorates as a result. The underlying biological mechanisms ultimately responsible for heat stress and stroke as a result of exposure to hot environmental temperature are initiated within the GI tract.

Hyperthermia Can Damage the GI Tract

As warm blooded animals are exposed to environmental temperatures greater than their thermoneutral temperature, the body reacts by trying to dissipate internal heat. Whole body hyperthermia causes a reduction in blood flow to the GI tract (Kregel et al., 1988). This allows a greater proportion of cardiac output to reach the periphery for heat dissipation (Rowell, 1974). However, shunting of blood flow from the GI tract to the periphery can result in intestinal cellular hypoxia (Hall et al., 1999), ATP depletion, acidosis, and cellular dysfunction (Gisolfi, 2000).

Combined, these cellular assaults can disrupt the GI barrier, allowing noxious compounds to enter the blood stream.

Stress-Induced Release of Corticosteroids Increases GI Tract Permeability

Meddings and Swain (2000) reported an increase in epithelial permeability in all regions of the GI tract after subjecting test animals to stress. They also reported that the elevated epithelial permeability was mediated by adrenal corticosteroids, as stress-induced increases in epithelial permeability disappeared after adrenalectomy or pharmacologic blockage of glucocorticoid receptors in test animals. Meddings and Swain (2000) also showed that dexamethasone treatment of control animals increased GI permeability and mimicked the effects of stress.

Elevated Gut Permeability Increases Lipopolysaccharide Absorption

The intestines normally contain large quantities of highly toxic lipopolysaccharides (LPS or endotoxin) sloughed from the wall of normally occurring intestinal bacteria (Sakurada and Hales, 1998).

It is normal for small amounts of LPS to cross the intestinal barrier. However, large increases in blood LPS concentration are an indicator of intestinal epithelial cell damage and elevated gut permeability. Lipopolysaccharides have been shown to increase in the blood of human heat stroke victims (Bouchama et al., 1991), exhausted ultra endurance runners (Brock-Utne et al., 1988), heat-stressed primates (Gathiram et al., 1988) and hyperthermic rats (Hall et al., 2001). This evidence shows a direct relationship between heat stress and intestinal damage.

LPS Absorption Induces Cytokine Release and Reduces Heat Dissipation

Above normal blood LPS concentration is detrimental. Elevated blood LPS levels have been shown to reduce cardiac contractility. This reduces heat tolerance by limiting cardiac capacity (Abel, 1989). In addition, elevated blood LPS concentration stimulates release of, and increases serum concentrations of the cytokines TNF-alpha and IL1- alpha (Hack et al., 1989).

Cytokines elevate the hypothalamic set-point for body temperature regulation. Cytokines activate thermoregulatory mechanisms within the body that act to reduce heat loss (such as reducing skin blood flow) and may increase body heat production by inducing fever (Hull et al., 1993). For pigs experiencing heat stress, cytokine release is not helpful as cytokines are antagonistic toward body heat dissipation.

Dietary Antibiotics Ameliorate Gut Damage and Permeability

Gathiram at al. (1987) explored the relationship between dietary antibiotics and gut permeability as measured by plasma LPS concentration. In this study, monkeys were given an oral, non-absorbable antibiotic for 5 consecutive days before being anesthetized and subjected to heat stress. Another group of anesthetized monkeys served as controls. As rectal temperatures increased from 99.5°F to 112.1°F, the plasma LPS concentration of the control animals rose significantly (P<0.01) from 0.044 ng/mL to 0.308 ng/mL. The plasma LPS concentration of the antibiotic-fed animals started at 0.007 ng/mL and remained unchanged as rectal temperature increased. The dietary antibiotic ameliorated the deleterious effects of heat stress to the GI tract.

Similarly, research conducted by Bynum et al. (1979) demonstrated better heat stroke survival in dogs after reducing the number of GI bacteria.

Bacitracin Can Reduce Gut Permeability

Bacitracin has long been recognized as the feed additive of “choice” for use in swine and poultry diets during the hot summer months. The performance-enhancing capabilities of bacitracin under conditions of heat stress were demonstrated by Manner and Wang (1991). In this 2×2 experiment, hens were subjected to a thermoneutral environmental temperature of 68°F or an environmental temperature of 93.2°F, with half the birds in each temperature treatment supplemented with zinc bacitracin. Performance of the heat-stressed, zinc bacitracin-supplemented hens was significantly better, with improvements of 66.3% in ADG, 5.9% in F/G, 15.4% in egg number, and 16.9% in total egg mass compared to heat-stressed, nonsupplemented hens. In addition, and even more fascinating, was the observation that fasting heat production was significantly reduced in the zinc bacitracin-supplemented hens by 4.1% and 7.6% in the 68°F and 93.2°F environments, respectively.

Cyclical Nature of Heat Stress

Environmental heat stress reduces blood flow to the GI tract and elevates plasma cortisol concentrations. These changes act to damage epithelial cells of the GI tract, resulting in cell death and opening of tight-cell junctions. As a result, gut permeability increases, allowing abnormally high fluxes of LPS and other toxins from the intestine to enter the blood. The LPS induce cytokine release and depress cardiac output, each of which acts independently to elevate internal body temperature, exacerbating the heat stress the animal is experiencing.

Summary and Application

Dietary bacitracin is not absorbed. Bacitracin blunts the cyclical nature of heat stress via its antimicrobial activity within the intestine. Bacitracin reduces gut permeability and promotes a healthy gut. A healthy gut acts as a defence barrier against toxic bacterial endotoxins, reducing their absorption. As a result, pigs consuming bacitracin perform more efficiently than their non-supplemented counterparts, especially during periods of stress.


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December 2008
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