Bacteria in intestinal contents are essential for disease to develop. Many defense mechanisms prevent bacterial damage. Peristalsis must continuously move food through the digestive system to protect against bacterial invasion and damage. Some protection depends on the diet. All nutritional needs can be given by total parenteral nutrition, but this reduces mucosal integrity so that bacteria can invade the mucosa. Dietary constituents that prevent bacterial translocation include nonfermentable fiber and specific nutrients such as glutamine. Glutamine is abundant in proteins.  This amino acid is important for energy and increasing blood flow in intestinal mucosa. Glutamine deficiency changes mucosal cell structure and function, causing atrophy and increasing permeability, and immunologic barriers are impaired. Glutamine also helps protect the mucosa during chemotherapy for cancer. Thus, feeding is important when intestinal mucosa is damaged.

  Managing Intestinal Mucosal Disease

What can be done about the three factors contributing to mucosal diseases? First, increased mucosal permeability can improve with management. Mucosal permeability depends on how an animal is fed. Feeding must be oral using a diet containing highly digestible proteins. Remission of inflammation, which follows feeding a controlled diet, coincides with reduced mucosal permeability. Any protein and energy deficiency must be corrected to reduce bacterial translocation. Protein deficiency also impairs the animal's immune defenses. The diet should contain some nonfermentable fiber (to reduce bacterial translocation) and fermentable fiber to provide colonic nutritional needs.^7,8 The products of bacterial fermentation of fiber, short chain fatty acids, are essential for normal colonic mucosal structure and function. Without short chain fatty acids, colonic blood flow, motility and fluid absorption are not normal; colitis develops. Mucosal permeability also depends on endotoxin in intestinal contents.⁹ Endotoxin levels reflect aerobic bacterial numbers in the intestine. Disease often increases total numbers for intestinal bacteria and shifts the population to endotoxin-producing bacteria. Certain diets reduce numbers of these bacteria and thus their endotoxin levels. Diets can thereby improve mucosal damage caused by a disrupted bacterial population. Commercial pet foods made from unwholesome ingredients can contain preformed endotoxin and contribute to disease. Feeding highly digestible noncereal sources of protein and correct amounts of protein is important for reducing colonic ammonia levels. No drugs are given unless they are essential to recovery. A very potent drug cyclosporin, which reduces inflammation and immune responses, worsens some cases of colitis. Excess of some dietary ingredients can promote inflammation. Fish oil is one example. Any fish or vegetable oil must be supplemented with vitamin E to minimize damage from rancidity in the oil. A more complete discussion follows.

Diets for Managing Intestinal Damage
Predigested and highly‑digestible diets protect the mucosa in problems other than inflammatory diseases. Intestinal mucosa is susceptible to damage during chemotherapy and in burn patients. Highly-digestible diets are protective by increasing life span for mucosal cells damaged by the injury. Mucosal cell structure and function recover slowly on conventional pet foods. Feeding a controlled diet based on cottage cheese or tofu and boiled rice or tapioca provides a highly-digestible diet and is beneficial. Predigested elemental diets are seldom required. They are expensive and poorly accepted because of their marginal palatability. Supplementing specials diet with glutamine may hasten mucosal recovery. Dogs with chronic diarrhea, due to unknown cause and so probably representing a dietary allergy, respond better to feeding cottage cheese or tofu-based diets than to feeding any other source of protein. The very high digestibility of cottage cheese contributes to its usefulness. The digestibility of tofu may not be as great but tofu has some unique properties for protecting intestinal mucosa. Certain anticancer drugs invariably cause anorexia and diarrhea because they damage intestinal mucosa. That damage occurs while feeding a controlled diet containing milk protein (cottage cheese or casein). While feeding soybean protein (such as tofu) the drug causes no damage.¹⁰ This protein protects the intestinal mucosa. Tofu diets will be more widely fed when these beneficial effects are better known. Humans with needs for bowel rest, efficient digestion and absorption, and digestive tract disease are often fed an enteral diet. Proteins in enteral diets are almost invariably of two kinds, soybean protein such as in tofu and casein which is the most important protein in milk or cottage cheese. Management of chronic gastric disease usually includes drugs for reducing gastric acid secretion. Diets can also reduce acid secretion. Meat-based diets stimulate greater gastric acid secretion than soybean protein (tofu) diets.¹¹ Tofu is the best protein to feed animals with gastric disease. Low‑fat diets are usually fed to animals with inflammatory bowel disease. When the total fat content of the diet is very low, animals recover well compared to feeding diets with 12 to 30 percent fat as the total calories. When dietary fats are mostly saturated, the response to dietary management of inflammatory bowel disease is good compared to feeding diets high in unsaturated fatty acids.¹² Feeding a high concentration of linoleic acid (such as corn oil) impairs recovery. Feeding a diet low in unsaturated fatty acids results in essential fatty acid deficiency. The consequence of the latter is less harmful than inflammatory bowel disease.

Fish-oil Diet for Managing Digestive Tract Disease
Special canine diets have been formulated with relatively large amounts of fish oil and marketed with the claim that they are beneficial for management of some inflammatory diseases. There are no clinical studies to show they are beneficial. In addition diets containing fish oil have a strong and offensive odor.

Fish Oils Effects on Inflammation¹³
Small animals require unsaturated fatty acids to produce the most important mediators of inflammation (leukotrienes). Some fatty acids (omega-3) are precursors for leukotrienes possessing a weaker ability to provoke inflammation than those made from the most abundant (omega-6) fatty acids. Fish oils have the highest concentrations of omega-3 fatty acids (with a few exceptions such as flax seed oil) that produce the less potent leukotrienes. Some pet food producers recommend feeding high concentrations of omega-3 fatty acid rich oils to manage inflammation. This reduces the formation of more potent leukotrienes. Theoretically, fortification with omega-3 fatty acids should aid in recovery from any type of inflammation. Diets enriched with highly unsaturated fats such as fish oil can cause intestinal inflammation, however. One reason is that fish oil diets reduce mucosal concentrations of prostaglandins. Prostaglandins are cytoprotective for gastrointestinal mucosa. The effects of reduced mucosal prostaglandin protection can be prevented by dietary antioxidants. High unsaturated fatty acid levels deplete compounds needed to protect against oxidative stress (formation of oxygen free radicals that destroy living tissue).¹⁴ Diets with high unsaturated fatty acid levels must contain additional antioxidants such as vitamin E. A high fish oil diet must contain more than usual amounts of vitamin E. Supplementation with vitamin E in animals with inflammatory bowel disease reduces mucosal damage. The beneficial effects of feeding omega-3 fatty acids may be negligible and any improvement is probably due to vitamin E acting as an antioxidant. It is much easier and less expensive to formulate a diet with vitamin E and no fish oil.

Fish-oil-enriched Commercial Pet Foods
Some manufacturers fortify pet foods with fish oil and recommend them for animals with skin disease such as pruritus due to fleas, allergies, and other inflammatory conditions. They also recommend these diets for management of gastrointestinal problems due to suspected food allergy and inflammatory diseases. The companies fortify the diets with omega-3 fatty acids so that the ratio of omega-6 to omega-3 fatty acids is between 5 to 1 and 10 to 1. Scientists evaluated the effects of feeding this diet by measuring concentrations of weakly and strongly proinflammatory leukotrienes in canine skin and some white blood cells.¹⁵ The diet reduces the strongly and increases the weakly proinflammatory leukotriene concentrations. Do these changes improve clinical signs?

Fish Oil Benefits Are Unproven
There are no studies evaluating clinical responses to feeding fish oil-enriched diets. They are of no proven benefit for skin or gastrointestinal diseases. Yet a pet food manufacturer promotes such products with the statement:

Continuing research provides compelling new insight into the effective dietary management of hypersensitivity. To help manage inflammation and pruritus in animals afflicted with common hypersensitivity disease, research strongly indicates that veterinarians and their clients should choose diets with optimal omega-6:omega-3 fatty acid ratios (5:1 to 10:1) and limited, highly digestible protein sources.¹⁶

Scientists studying human problems conduct most of the research on these diets. Their conclusions differ from those promoting diets for feeding small animals. In a review Evolving Medical Therapies for Inflammatory Bowel Disease the author states:

Other potential sites of eicosanoid inhibition include the diversion of mediators away from the 5-LO pathway to less "pro-inflammatory" derivatives as has been accomplished to a modest degree by the administration of high concentrations of omega-3 fatty acids (fish oils). Clinical trials using high doses have demonstrated more biochemical effects than clinical benefits. The latter are overcome by a fishy odor and potential impact on coagulation.¹⁷

In summary, the fish oil diets show questionable clinical benefits, are smelly, and can cause problems by promoting bleeding. Diets rich in unsaturated fatty acids also have the potential for causing diarrhea. In addition, the animal diets are expensive—with a cost that is double that of comparable foods not fortified with fish oil—yet with no proven value.

 Feeding Foods Containing Nucleotides

Requirement for Nucleotides¹⁸
Most dietary nitrogen is in protein with nitrogen being an important part of every amino acid. Nitrogen is also a part of nucleotides that are essential to biochemical operations of all cells. Nucleotides are necessary for the production, use and storage of cellular energy. They form DNA and RNA structures necessary for the genetic code and cellular protein production. Some nucleotides are messengers for biochemical events and they can be part of enzyme systems. Nucleotides are necessary for normal intestinal structure and function and they promote gastrointestinal healing. Cottage cheese or tofu and rice or tapioca diets are low in nucleotides. Since there are no nutritional requirements established by the National Research Council for nucleotides in small animals this does not represent a deficiency. Part of the reason for this is that the body synthesizes nucleotides. Their production is costly in terms of energy, however. Thus, if a diet contains nucleotides, it will be easier for an animal to maintain the functions with which they are involved. Supplementing diets with nucleotides has proven effects to optimize gastrointestinal growth and regeneration. Animals with diarrhea or intestinal damage recover more quickly when fed diets containing nucleotides. This diet provides nucleotide precursors for mucosal renewal and for improved mucosal circulation. This diet also can promote a most favorable intestinal bacterial population. Nucleotides help maintain intestinal immune responses that are essential to prevent invasion by intestinal bacteria. This is most important for immunocompromized animals. The liver is important for making and exporting nucleotides. If disease compromizes liver function as well as that of the intestinal tract the liver is unable to maintain this function. Dietary nucleotides help here in recovery of both hepatic and intestinal diseases.

Nucleotides Added to The Diet
The diet should be supplemented with nucleotides for animals recovering from gastrointestinal disease. Red meats are higher in nucleotides than most other foods. Meats are not included in the diets for gastrointestinal disease because many dogs will not recover when they are fed meat. Thus, it is necessary to add another source of nucleotides. Non-meat sources include asparagus, cauliflower, beans, lentils, peas, mushrooms, and spinach. In some animals fish and poultry are acceptable sources. Some of the diets shown in this website have recipes supplemented with nucleotides. They include the cottage cheese or tofu and boiled rice diets that are enriched with one kind of nucleotide, purines.

Feeding Foods Containing Polyamines¹⁹
Polyamines are small compounds made from a few select amino acids. Specific ones have unusual names such as spermine, cadaverine and putrescine. The intestinal mucosa (and other tissues in the body) manufactures them. The diet also supplies polyamines. Polyamines promote growth and multiplication of cells. Specific effects of polyamines include the ability to promote hypertrophy and hyperplasia of gastrointestinal mucosa, inhibit gastric acid secretion, promote ulcer healing, prevent development of experimentally induced ulceration, and induce intestinal maturation and the development of digestive enzyme activity. Polyamine deficiency slows recovery in diseased mucosa.  With damage, fewer cells are available to produce polyamines. If the diet is deficient in polyamines, healing is even slower. Normal intestinal structure and function cannot return until the mucosa heals. Restoration of the mucosa takes about a week and that requires optimal amounts of polyamines. The diet should contain adequate polyamines and precursors for their formation. Soybean isolates are very high in polyamines. In contrast milk-protein based diets are very low in polyamines. The diets containing tofu are high in polyamines, and the cottage cheese diets contain low amounts. The digestive tract's requirement for polyamines can be shown by using inhibitors of polyamine formation. Such inhibitors are used to treat malignantly growing cells in the digestive system. Inhibitors reducing polyamine levels slow cancer cell growth and multiplication. Reducing dietary polyamine levels has the same effect.

 Resting and Cleansing the Intestinal Tract⁴

With colonic contents containing many substances necessary for damage and inflammation, their removal would benefit in managing colonic disease. In the 1950's veterinarians frequently gave dogs enemas to treat acute digestive tract diseases. Giving large amounts caused fluid movement into the small intestine and some was vomited. Giving enemas until dogs vomited was helpful but for reasons unknown at the time. Animals with acute intestinal tract damage heal faster when intestinal contents are washed out. Both structure and function return to normal faster. Healing is slower when drugs are used to retain contents in the intestine. Motility modifiers such as loperamide cause such a retention. Continued exposure of the injured intestinal mucosa to intestinal contents stimulates inflammation. Cleansing the intestine prevents inflammation and any injury heals without being delayed by inflammation. Cleansing is the only way to remove bacteria and toxins such as endotoxin. Other substances such as certain foods are eliminated by not feeding commercial pet foods; nothing or a controlled diet is fed.

Intestinal Tract Healing Takes Time
When feeding is resumed for animals with intestinal damage, digestion remains abnormal until mucosal cells regain their ability to produce and secrete digestive enzymes. Animals lose that ability and do not regain it for five to seven days, the time necessary for renewal of the cells producing enzymes. Mucosal damage also impairs nutrient absorption; five to seven days is required for its recovery. A great mistake made in caring for animals recovering from mucosal damage is to continue feeding a commercial pet food that is not adequately digested and absorbed. With incomplete assimilation, gut contents contain foods that can be absorbed and provoke an allergy. Owners often wish to feed a commercial pet food after signs of gastrointestinal problems disappear. Commercial food should not be fed when allergy to a food can develop. Unfortunately, recovery can appear to be complete long before intestinal mucosa is normal. Diarrhea, vomiting and inappetite disappear days before recovery is complete. Animals will usually beg for food at this time and owners give them what they want.

Summary
Care and feeding of animals with gastrointestinal problems, causing chronic diarrhea and sometimes persistent vomiting, requires a protocol that causes the most favorable environment for healing. This protocol is based on selecting a diet that is optimally digested and absorbed. No drugs are given unless there are specific indications or dietary management fails. Healing requires management for at least a week before it is complete. With a food allergy it may require months before oral tolerance is regained. Continuing to feed offending foods, even in small amounts that cause no signs of diarrhea, will cause allergies to persist; tolerance for food is never regained.

References
1. Guilford, W. Grant. 1996. Gastrointestinal Immune System. In Strombeck’s Small Animal Gastroenterology, 2d ed. edited by W. Grant Guilford, Sharon A. Center, Donald R. Strombeck, David A. Williams and Denny J. Meyer, 20-39. Philadelphia: W.B. Saunders.

2. Guilford, W. Grant. 1996. Gastrointestinal Inflammation. In Strombeck’s Small Animal Gastroenterology, 2d ed. edited by W. Grant Guilford, Sharon A. Center, Donald R. Strombeck, David A. Williams and Denny J. Meyer, 40-49. Philadelphia: W.B. Saunders.

3. Boedeker Edgar C. 1994. Adherent Bacteria: Breaching the Mucosal Barrier? Gastroenterology 106(1):255-257.

4. Guilford, W. Grant and Donald R. Strombeck. 1996. Classification, Pathophysiology, and Symptomatic Treatment of Diarrheal Diseases. In Strombeck’s Small Animal Gastroenterology, 2d ed. edited by W. Grant Guilford, Sharon A. Center, Donald R. Strombeck, David A. Williams and Denny J. Meyer, 351-356. Philadelphia: W.B. Saunders.

5. Meyer H. and E. Kienzle. 1991. Dietary Protein and Carbohydrates: Relationship to Clinical Disease. Purina International nutrition symposium in association with the Eastern States Veterinary Conference, January 15, Orlando, Florida. 13-26.

6. McArdle, A. Hope. 1994. Protection from radiation injury by elemental diet: does added glutamine change the effect? Gut supplement 1:S60-S64.

7. Bauer, John E. and Ian E. Maskell. 1994. Dietary Fibre: Perspectives in Clinical Management. In The Waltham Book of Clinical Nutrition of the Dog and Cat. Edited by J. M. Wills and K. W. Simpson, 87-104. Oxford: Pergamon Press.

8. Deitch, E. A. 1994. Bacterial translocation: the influence of dietary variables. Gut supplement 1:S23-S2

9. Ciancio, Mae J. 1994. Endotoxin-induced diarrhea in inflammatory bowel disease: cellular and molecular mechanisms. Progress in Inflammatory Bowel Disease 15(1):17

10. Funk, Martha A. And David H. Baker. 1991. Effect of Fiber, Protein Source and Time of Feeding on Methotrexate Toxicity in Rats. Journal Nutrition 121:1673-1

11. McArthur, K. E., J. H. Walsh and C. T. Richardson. 1988. Soy protein meals stimulate less gastric acid secretion and gastrin release than beef meals. Gastroenterology 95:920-926.

12. Fernandez-Banares, F., E. Cabre, F. Gonzalez-Huix, and M. A. Gassull. 1994. Enteral nutrition as primary therapy in Crohn’s disease. Gut supplement 1:S55-S59.

13. Drevon Christian A. 1992. Marine Oils and Their Effects. Nutrition Reviews, 50(4):38-45.

14. Aw, T. Y., C. A. Rhoads, D. F. Smith, R. Iwakiri and J. R. Zahn. 1994. Intestinal Inflammation and Oxidative Stress Are Associated with Fish Oil Feeding in the Rat. Gastroenterology    A647.

15. Vaughn, D. M., G. A. Reinhart, S. F. Swaim, S. D. Lauten, M. K. Boudreaux, J. S. Spano and C. Hoffman. 1994. Evaluation of Dietary N-6 to N-3 Fatty Acid Ratios on Leukotriene B Synthisis in Dog Skin and Neutrophils. Journal Veterinary Internal Medicine, 8(2):155.

16. Anonymous. 1994. New concepts in Pruritic Management. in Topics In Practical Nutrition, Lewisburg: The IAMS Company, 4:3

17. Hanauer, Stephen B. 1994. Evolving Medical Therapies for Inflammatory Bowel Disease. Progress in Inflammatory Bowel Disease, 15:(2)1-5.

18. Grimble G. K. 1994. Dietary nucleotides and gut mucosal defence. Gut supplement 1:S46-S51.

19. McCormack, Shirley A. and Leonard R. Johnson. 1991. Role of polyamines in gastrointestinal mucosal growth. American Journal Physiology (Gastrointestinal Liver Physiology 23):G795-G806.

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