PROTEINS AND AMINO ACIDS

The layer of epithelial cells that lines the intestines forms a continuous sheet throughout the intestine. These cells are renewed continuously from stem cells in the crypts such that intestinal epithelial cells are replaced about every three days. This rapid regeneration helps the intestine to heal quickly following an injury, but the continuous turnover of cells exerts a high demand for nutrients. These cells use between 10 and 20 per cent of total energy expenditure and approximately 50 per cent of ingested protein, with more than 90 per cent of the aspartate, glutamate, and glutamine used by the intestinal tissues.¹ Therefore the GI tract is highly sensitive to protein or amino acid deficiency.

Inadequate intake of dietary protein or essential amino acids can cause GI tract atrophy with a decrease in absorptive cells, alterations in digestive enzymes, reduction in immunoglobulins and immune cells in the intestine, and an increased risk for colonization and translocation of pathogenic microorganisms.^2–5 Dietary protein deficiency also can lead to atrophy of the pancreas and a reduction in digestive enzymes. Correction of the protein deficit before the condition reaches an irreversible stage restores normal function.

The amino acids glutamine and glutamate are critical for the health of the GI tract, where they serve as key energy sources. In addition, glutamine promotes the natural barrier function of the intestinal mucosa.⁶ Glutamine often is cited as a “conditionally essential” amino acid because inadequate quantities may be produced under certain conditions, such as with limited food intake.⁷ If dietary glutamine is excluded following intestinal injury, the intestinal mucosa atrophies and bacterial translocation from the intestinal lumen can occur. However, glutamine is found abundantly in meat and other proteins and normally is made in the body from other amino acids. As long as dietary protein intake is sufficient, additional glutamine is not of benefit.

Adequate protein and amino acid intake is critical to promote intestinal healing, and protein does not appear to contribute to diarrhea. Cats are unique in requiring a much greater intake of dietary protein compared with dogs and most other species. When preservation of lean body mass in healthy cats was used as the criterion for protein adequacy, about 5 g/protein per kg body weight, or about 9 g/100 kcal metabolizable energy, was needed daily.⁸ Additional protein may be of benefit in situations of low calorie intake, dietary malabsorption, or protein-losing enteropathy (PLE).

Dietary protein increases the rate of gastric emptying in other species, but this does not appear to be true for cats. In cats, a high-protein meal actually slowed gastric emptying time, and gastric emptying was faster with a high-fat diet.⁹ Therefore a high-protein diet may be of benefit in cats with diarrhea by slowing the rate at which the compromised GI tract must process the incoming nutrients.

On the other hand, proteins are implicated in food allergy–induced diarrhea. Not all adverse reactions to food are true allergies. Animals (and human beings) can have idiosyncratic reactions to any food component independent of an immunological response. Thus food intolerance includes both immunological (allergic) and nonimmunological (idiosyncratic) responses. Food allergies are caused by an abnormal immunological response to normal proteins in the intestine. Most often, these appear to be dietary proteins, but bacterial proteins also have been implicated. This will be addressed in more detail in the section on food allergy.

FATS

Compared to protein and carbohydrate, fat digestion is more complex. The stages include intraluminal digestion; micellar solubilization; permeation from the lumen to the cell; intracellular re-esterification; chylomicron formation; and transport via the lymphatic circulation. For complete digestion, this requires lipase, colipase, and phospholipase A₂ from the pancreas, as well as bile acids that are produced by the liver, then stored and released from the gall bladder. Once inside the enterocyte, fatty acids and monoglycerides must be reformed into triglycerides. This is an active, energy-expending process, resulting in production of chylomicrons, which then enter into the intestinal lacteals and are transported via the lymphatic system to the systemic bloodstream. This differs from other nutrients, which are transported directly to the liver via the portal blood.

Despite the complexity, fat digestion is highly efficient so that most ingested fat is absorbed in healthy subjects. Yet, because of the complexity, fat digestion is compromised easily. When fat digestion is incomplete, bacteria in the colon can ferment the undigested fat, producing potent secretagogues and proinflammatory compounds. This results in a secretory diarrhea as well as intestinal inflammation. Thus, low-fat diets have long been recommended for animals with GI disease and diarrhea. However, cats appear to respond differently to fat compared with dogs and other species. In most species, fat is thought to slow the rate of gastric emptying, leading to an increased risk for vomiting and delayed gastric emptying. In cats, fat appears to have an opposite effect and cats fed a high-fat diet actually had faster gastric emptying.⁹ Dietary fat also appears less important in the management of some types of chronic diarrhea in cats. In a double-blinded clinical trial evaluating the effect of high-fat versus low-fat diets in cats with diarrhea, there were no differences between the diets in terms of clinical response.¹⁰

CARBOHYDRATES

There is an often repeated, yet incorrect, perception that cats do not digest carbohydrates well. Cats, like dogs, do not have salivary amylase, but intestinal digestion of starches is initiated by pancreatic amylase, and completed by enzymes at the intestinal brush border. The brush border enzymes include sucrase, maltase, isomaltase, and lactase. Although some reports indicate low levels of enzyme activity in cats, others have demonstrated that the activity of these brush border enzymes, especially sucrase and maltase, is greater in cats than in dogs.¹¹ Cats may not handle large amounts of simple sugars well, but they are able to digest starches and other carbohydrates efficiently.^11,12 Even lactose is not an issue for normal cats, despite the perception that many cats are lactose intolerant. Relatively recent research showed that 10 per cent dietary lactose (1.2 g/kg body weight) in normal cats did not affect stool quality.¹³

With intestinal disease, however, carbohydrate digestion may decrease. The disaccharidases that complete the digestion of carbohydrates are located in the small intestinal brush border, which may be damaged due to disease. Increased carbohydrate fermentation, indicative of carbohydrate malabsorption, has been confirmed by breath hydrogen testing in cats with inflammatory bowel disease (IBD).¹⁴ Carbohydrate malabsorption may occur in IBD if inflammation inhibits production of digestive enzymes, or if inflammatory infiltrates compromise nutrient absorption.¹⁴

When carbohydrate malabsorption does occur, it can contribute to osmotic diarrhea, as well as bacterial overgrowth and other problems. In such cases, avoidance of carbohydrates may help manage the clinical signs of diarrhea. One clinical study indicated that about 58 per cent of cats with chronic diarrhea improved when fed a low-carbohydrate (15 per cent dry matter) dry diet.¹⁵

DIETARY FIBER

Although dietary fibers are carbohydrates, their physiological effect is very different from digestible carbohydrates. Dietary fibers are structurally similar to starches and other digestible carbohydrates in that they are composed of strings of sugar molecules bound together. However, unlike digestible carbohydrates, which are linked with an alpha linkage that is cleaved easily by mammalian alpha-amylase, the sugars in dietary fiber are linked by a beta linkage. Beta links between sugar molecules are not digestible by mammalian digestive enzymes, but are cleaved by bacterial enzymes, so these substrates remain intact until digested (fermented) by bacteria.

Dietary fibers can be classified in many different ways, although the most common are based on the water solubility of the fiber or the fermentability by microorganisms. Although there are exceptions, it is generally recognized that more soluble fibers tend to be more fermentable. The functionality of dietary fibers is related to these two characteristics. Soluble fibers tend to form viscous gels, which can slow gastric emptying and GI transit. Insoluble fibers tend to adsorb water and increase fecal bulk, which can help normalize GI motility. Highly soluble fibers are found in pectins, gums, psyllium, and oligofructoses. Cellulose and most brans are examples of insoluble fibers. Many fibrous ingredients in foods and pet foods contain differing degrees of both soluble and insoluble fiber (Table 8-1). Likewise, the fermentability of fibers in pet foods varies. Cellulose undergoes little fermentation, pea fiber and soybean hulls are moderately fermented, while beet pulp can be highly fermentable.

Table 8-1 Characteristics of Some Fibrous Ingredients Used in Pet Foods or Supplements

Insoluble fibers tend to adsorb water and add bulk to intestinal contents and feces. This provides several benefits for GI health. The bulk stimulates GI motility and peristaltic movements, preventing gut stasis and promoting regular bowel habits. The spongelike effect of adsorbing water helps soften stool to aid in passage. Also, the bulk provides a dilutional effect for any endogenous or exogenous toxins that might be present in the bowel, reducing the likelihood of adverse effects.

Soluble, fermentable fibers serve as a substrate for the intestinal microflora to produce short chain fatty acids (SCFAs): acetate, butyrate, and propionate. SCFAs provide an energy source for colonocytes, stimulate colonic blood flow, promote water absorption, and promote growth and cellular turnover in the lower intestine. In addition, SCFAs help lower the pH of intestinal contents, which inhibits the growth of pathogenic bacteria. The lower pH also can reduce the absorption of some toxins, including ammonia. Dietary fibers, especially fermentable fibers, also can modulate properties of the immune system, likely through their effects on intestinal microflora.¹⁶ Due to the various effects of both soluble and insoluble dietary fibers, they may be of benefit in the management of GI disease, especially diseases of the large bowel. Excessive soluble fiber, however, will cause loose, watery stools, and can cause the production of excess gas, while excess insoluble fiber can contribute to excessive stool volume, and may reduce absorption of some essential nutrients.

A subset of fermentable fibers includes prebiotics. By definition, these fibers are fermented selectively by health-promoting bacteria, especially strains of Lactobacillus and Bifidobacteria.^17,18 This results in their ability to increase the number or percentage of these organisms, while decreasing the prevalence of potential pathogens, such as Salmonella, Clostridia, or E. coli. Prebiotics also produce some of the health benefits generally associated with dietary fibers, such as reducing blood lipids and cholesterol, reducing constipation, and aiding in various types of diarrhea and inflammatory conditions of the GI tract, as well as being a substrate for SCFA production.^17–19 Among the many fibers available for use as prebiotic supplements are beta-glucans; pectin; resistant starch; various oligosaccharides, such as inulin, fructooligosaccharide (FOS), and mannanoligosaccharides (MOS); and others.^19–21

PROBIOTICS

Although not a nutrient, probiotics are potential dietary components that may be of value for GI health. Probiotics are live microorganisms, consumed in food or supplements, that affect the host beneficially by improving its microbial balance and by interacting with the gut-associated lymphoid tissue (GALT). The GALT is the largest immunological organ in the body as it contains all of the lymphoid tissue, nodules, Peyer’s patches, and individual lymphocytes found in the intestinal walls. About 70 to 80 per cent of the immunoglobulin-producing cells of the body are located in the GI tract.²⁰ Stimulation of the immune system within the GI tract also can result in effects throughout the body. Activated plasma cells migrate to the bloodstream and to other parts of the body. Therefore antigen priming at one surface area (the intestinal mucosa) can result in antibodies being synthesized and secondary responses occurring at other sites. Through this mechanism, probiotics interacting with the GALT can influence GI and systemic health and immune function.

Some of the most commonly fed probiotics include Lactobacillus species, Bacillus subtilis, and Enterococcus faecium SF68.²² Multiple meta-analyses of clinical trials in human beings have confirmed the benefit of probiotics in the control of antibiotic-associated diarrhea.^23,24 Probiotics have proven beneficial in the management of acute diarrhea, viral and bacterial diarrhea, and IBDs, reducing either the duration, severity, or both.^25–28 In a murine model of sepsis, probiotics were able to prevent the breakdown in colonic barrier function and reduce bacterial translocation and liver injury.²⁹ Such data are not yet available for cats, but probiotics have been evaluated in a number of animal studies.

In dogs, the probiotic Enterococcus faecium SF68 provides several documented benefits, including enhanced response to vaccination and increased intestinal IgA.³⁰ In piglets, this probiotic reduced the development of diarrhea, decreased mortality, and enhanced growth performance.^31,32 In kittens, this same probiotic increased fecal bifidobacteria and decreased C. perfringens, increased serum IgA concentrations, and reduced the severity and incidence of diarrhea significantly during a natural outbreak in the colony.²² The probiotic Lactobacillus acidophilus also was confirmed to beneficially alter fecal microflora and markers of immune function in healthy cats,³³ and a probiotic containing both Lactobacillus and E. faecium enhanced fecal quality effectively in captive cheetahs prone to diarrhea.³⁴ (See Chapter 11 for a complete discussion on probiotics.)