Probiotics and Prebiotics:

Diet and Health in Pets

Both of these subjects have received significant amount of attention in the past decade for medical patients of all species. The public is now been exposed to these concepts through advertising campaigns for items such as Activia® fortified yogurt and Cheerios® for their respective cultured probiotic bacteria and lipid-regulating ingredients. The benefits may be overstated by some companies, and the FDA has taken some claims to task; however, the fact is that we and our pets are well in the grip of a manmade, urbanized group of diseases unique to industrialized countries. Dietary intake and lack of exercise underlie most of them: obesity. High blood pressure, diabetes, arthritis, fatty livers and metabolic syndrome are rare afflictions in third world societies without the benefits of modern technology. Refrigeration and mass factory food production has taken us days to months away from the production site for meats, dairy, produce and pet food. Sterilization and pasteurization have wiped out probiotics from our diets (pets and owners alike), while the trend toward consumption of processed meats and starches have dropped fiber intake dramatically. A hundred plus years ago, the American diet was rich in whole grain breads, raw milk, fermented (blue) cheeses, homemade yogurt, fermented milk (buttermilk, kefir, etc), dried fruits, nuts, local butchered meat. Dogs would have been fed directly from the table while cats were forced to eat whole raw wild prey to survive.

While medical science has spent decades and trillions of dollars finding out how disease mechanisms work, much less is actually known about how the natural balance of food, nutrition and digestive systems work to our advantage. This is still a poorly defined discipline, but some very good information has come to light that may be of medical value to you and your pet’s long term health. The appearance of diseases such as Inflammatory Bowel Disease (IBD), Lymphocytic-Plasmacytic Enteritis, Nervous Colitis and Crohn’s disease are modern phenomena. The most severe forms of IBD have the least amounts of probiotics in the gut ecosystem.

New data suggests that the real answers were at hand all the time: evolution and nature knows best and violating dietary rules that evolved over millions of years can have negative consequences. Simply put, eating a more traditional diet (whole grains, fiber-rich, low fat, organic diets for dogs and people, plus grain-free organic canned diets for cats) is best suited for each species’ normal physiology.

Probiotics:

The idea that probiotics may exist and are important to everyday health came from trying to explain why patients with diarrhea and gut upsets failed to get better after treatment with antibiotics. Patients treated for long periods with drugs for diarrhea often had continued to suffer. This could be due to clinical treatment for loose stools or intentionally in preparation for intestinal surgery to reduce the risk of contamination in the belly. Either way, many patients had substantial difficulties in reestablishing normalgut health. Many patients eventually turned to alternative medicine practitioners for nutritional and herbal therapy to combat the unrelenting yeast infections that often accompany these conditions. Cultures showed only pathogenic bacteria (Small Intestinal Bowel Overgrowth Syndrome aka SIBO), or no bacteria at all on post treatment samples Eventually, this condition came to recognized as dysbiosis. Dysbiosis (aka dysbacteriosis) is defined as “an imbalance in the intestinal bacteria that precipitates changes in the normal activities of the gastrointestinal tract or vagina, possibly resulting in health problems”.

This work led to the recognition that beneficial bacteria are essential for normal intestinal and female reproductive tract function. This makes great sense in terms of evolution where certain bacteria and microorganisms would be employed to aid in digestion and stabilization of the gut micro-ecology beyond that of simple chemical action from stomach acids, bile salts and pancreatic juices of the digestive organs. This is even more critical in the cat’s gut system where there are ten time the concentration of bacteria than that of humans or dogs.

At the start of the 20th century, probiotics were simply thought to be beneficially affecting the host by improving its intestinal microbial balance, thus inhibiting pathogens and toxin producing bacteria. These pathogenic bacteria are present in the vast majority of healthy normal pet guts (approximately 75% of dogs and cats) but have substantially elevated numbers present during gut upset episodes. It has been traditionally assumed that “good bacteria” kept the ever-present introduction of pathogens (“bad bacteria e.g. E. coli, Salmonella, etc) from multiplying to cause diarrhea. Today, additional specific health effects are being documented, including alleviation of chronic intestinal inflammatory diseases, prevention and treatment of pathogen-induced diarrhea, urogenital infections, and allergic (atopic) diseases. Essentially all significant published research is in humans using cultured bacteria administered to patients. However, Drs. Deb Zoran at the Texas A&M University College of Veterinary Medicine GI labs and Mike Lappin at the Colorado School of Veterinary Medicine are leading the way in this very complicated and exciting field. Feeding of probiotics appears to reduce either the incidence or the intensity of many diseases in both cats and dogs. These are empirical observations so far, and disease mechanism studies are currently underway.

The probiotic bacteria Bifidobacteria was first isolated in 1899 from a breast-fed infant by Dr. Henry Tissier at the Pasteur Institute. Tissier found that bifidobacteria are dominant in the gut flora of breast-fed babies and he observed clinical benefits from treating diarrhea in infants orally with cultured samples of bifidobacteria. He claimed the effect was that bifidobacteria displaced the pathogenic bacteria causing the diarrhea, hence the origins of the pathogenic bacteria repression theory.

Research is emerging on the potential health benefits of multiple probiotic strains as a health supplement, as opposed to use of a single strain, such as Lactobacillus (LaB) alone. The human gut is home to at least some 400-500 types of microbes. Genomic sequencing studies at the TAMU GI laboratory suggest that dogs may have as many as 700 species of normal flora based on DNA primers optimized for the sequencing of the

16S rRNA gene fragment in the ribosome (a conserved protein factory organelle in every cell). It is thought that this diverse ecosystem may benefit from giving multiple probiotic strains at one time; different strains populate different regions of the digestive tract, and studies are beginning to link different probiotic strains to specific health benefits. The environment in the stomach, small intestines and large bowel are vastly different, and their normal gut flora bugs are respectively different, as well. For instance, different species of Lab are restricted to the jejunum, ileum or colon.

Probiotic therapy may restore or supply essential bacterial strains needed for gut maturation and homeostasis, particularly in hosts where this process has been disrupted. Additional potential mechanisms of beneficial probiotic interactions with immature intestinal epithelia include immunomodulation, upregulation of cytoprotective genes, prevention and regulation of apoptosis (noninflammatory cell death) and maintenance of intestinal barrier function to transmigration of bacteria into the blood stream. Potential mechanisms of therapeutic effect elucidated by animal models and human clinical studies implicate modulation of T-cell helper type 2 (TH2-type) actions in allergic inflammation and induction of immune tolerance.

A systematic review of nine placebo-controlled studies in children and adult humans using various probiotic products showed a 60% reduction in incidence and duration of antibiotic-associated diarrhea compared with placebo in a 2002 study. A two year follow- up showed no difference in neonatal morbidity, colic, or serious adverse effects, such as significantly fewer antibiotics prescribed to the treated (symbiotic) group and fewer respiratory infections. Animal studies are in the rudimentary stages due to the limited funding to veterinary colleges and the overwhelming volume of required testing of the approximately 700 different probiotics in different doses and in all possible combinations. On a clinical level, use of commercially available freeze dried cultured capsules and plain yogurt (cow, sheep, buffalo) will effectively control or significantly reduce the damage process for about 20% of any patient population for diarrhea, gastric reflux, dysbiosis, IBS, irritated bowel, nervous colitis. It is an excellent means of reducing or eliminating gas (flatulence) in breeds prone to this social offense (bulldogs, pitbulls, labs, retrievers, etc). A large tablespoon of plain yogurt twice daily provides a wide spread of probiotics, while a Powerdophilus® capsule (Whole Foods Market) once daily will provide 5 probiotics in the 10 billion colony forming units (CFU = live bacteria) range for each organism at a cost of less than 15¢ per day. All probiotic sources ARE NOT EQUAL. A consumer report study showed around 80% of all OTC commercial probiotic products tested in supermarkets, drugstores and nutritional outlets were not potent (less than labels content) or nonviable (dead bacteria). In contrast, plain yogurt was found to be equal in CFU content and viability from all sources.

Several new mechanisms by which probiotics exert their beneficial effects have been identified and it is now clear that significant differences exist between different probiotic bacterial species and strains; organisms will need to be selected in a more rational manner to treat different diseases. Mechanisms contributing to altered immune function in vivo induced by probiotic bacteria may include modulation of the microbiota ecology itself,

improved barrier function with consequent reduction in immune exposure to microbiota, and direct effects of bacteria on different epithelial and immune cell types. It is thought that perhaps each of the hundreds of probiotics activate or repress individual T-cell lymphocyte function via cell-to-cell referred signaling through cytokines present in the gut epithelial wall.

A note of caution is appropriate here. Despite the huge potential for probiotic, colostrum and other immunomodulating therapies; results from meta-analyses and systematic reviews that combine results of numerous studies from different types of probiotics to examine the effects in any disease state should be interpreted with caution. Specific strains alone, or in combination, are effective in treating very specific disease states. No two probiotics are exactly alike; we should not expect reproducible results from studies that employ different species or strains, variable formulations, and diverse dosing schedules.

Prebiotics:

As a functional food component, prebiotics, like probiotics, are conceptually placed intermediately between foods and drugs. Typically, prebiotics are carbohydrates (such as oligosaccharides aka small sugar molecules), but the definition may also include non- carbohydrates. The most prevalent forms of prebiotics are nutritionally classed as soluble fiber. To some extent, many forms of dietary fiber exhibit some level of prebiotic effect. The term often applied to this class of nutrition is “functional foods”. These are not the only members of this class, but have received the most attention recently. Simply put, prebiotics give probiotic bacteria something beneficial to eat and help further stabilize the micro-ecology of the intestines.

Dr. M. Roberfroid, who first identified the importance of prebiotics offered a definition in the 2007 Journal of Nutrition stating: "A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity, in the gastrointestinal microflora that confers benefits upon host well-being and health."

The United Nations Food and Agricultural Organization defined prebiotics as “a nondigestible food ingredient that promotes the growth of beneficial microorganisms in the intestines”.

Natural sources containing various prebiotics include breast milk, raw dandelion greens, leeks, onions, garlic, asparagus, whole grains, beans, banana, soybeans, inulin sources (such as Jerusalem artichoke, jicama, and chicory root), raw oats, unrefined wheat, unrefined barley and yacon (a fibrous tuber grown in the Andes mountains). Some of the oligosaccharides that naturally occur in breast milk are believed to play an important role in the development of a healthy immune system in infants. Obviously, some of these food options pose toxic risks to pets (onions, garlic and possibly leeks, cause anemia). Oatmeal is a soluble fiber source that holds great benefits for dogs. The individual ingredients can be fed to cats as food supplements.

It is becoming more common to properly distinguish between prebiotic substances and the food that contain them, as references to almonds, honey and other foods (most

commonly by growers of those foods) as "a prebiotic" are not accurate. No plant or food is a prebiotic: Wheat, honey and many other foods contain prebiotics to a greater or lesser extent, ranging from fairly large portions (chicory root, Jerusalem artichoke) to only trace quantities (thousands of other plant-based foods). Referring to a food as "a prebiotic" is no more accurate than calling a food "a vitamin."

Common purified prebiotics in use include inulin, fructo-oligosaccharides (FOS), galactooligosaccharides (GOS), soya-oligosaccharides, xylo-oligosaccharides, pyrodextrins, isomalto-oligosaccharides and lactulose. These compounds have been studied to varying degrees in animal feeding studies. They may be currently found as additives in some commercial pet foods. Be careful to limit the amounts of each prebiotic to a half teaspoon or less for pets, as too much fermentable fiber can create painful gas production. 1⁄4 tsp will be adequate for dogs 10 to 30 lbs while a half tsp daily will be effective for dogs between 50 and 80 lbs. Dogs over 80 lbs may need 3⁄4 to one tsp daily while small dogs and cats will do best on am 1/8th of a tsp in wet food.

Studies have demonstrated positive effects in human patients on calcium and other mineral absorption, immune system effectiveness, bowel pH, reduction of colorectal cancer risk, inflammatory bowel disorders (Crohn's Disease and Ulcerative Colitis), hypertension (high blood pressure) and intestinal regularity. Recent human trials have reinforced the role of prebiotics in preventing and possibly stopping early stage colon cancer. It has been argued that many of these health effects emanate from increased production of short-chain fatty acids (SCFA) by the stimulated beneficial bacteria, which are widely recognized to be beneficial to the host. Purified inulin, FOS, GOS (dogs and cats) and uncooked instant oatmeal added to the diet (dogs) has been used successfully in cases of chronic diarrhea that resist response to more traditional medications, despite a lack of statistical, evidence-based medical proof. Lactulose should be avoided at the current time due to its laxative nature.

Generally, it is assumed that a prebiotic should increase the number and/or activity of bifidobacteria and Lactobacilli where these groups of bacteria have several beneficial effects on the host, especially in terms of improving digestion (including enhancing mineral absorption) and the effectiveness and intrinsic strength of the immune system. This stipulation of selective fermentation or selective increase in growth and/or activity within the current definition has become synonymous with the observations of preferential increase in bifidobacteria and/or Lactobacilli species in the intestines treated with prebiotics. However, it is now inadequate to describe a beneficial modulation of a restricted microbiota population dominated only by a few members of the Clostridium and Bacteroides species, regarded as key species together with the bifidobacteria in dietary foodstuff sugar (simple carbohydrate) fermentation within the colon. These considerations and their implications warrant a reconsideration of the prebiotic definition and their actions on a complex ecosystem. The difficulty is how to encompass the entire field in a simple statement, since so much remains unclear.

A great source can be found on the web at http://www.jarrow.com/product/457/Inulin_FOS made by Jarrow Formulas and purchased at http://www.iherb.com/Inulin. A great option combines probiotics

and prebiotics in Jarro-Dophilus® + FOS. These are also available at Pets Naturally and Capitol Drug in Sherman Oaks, CA.

A more extensive review of these subjects plus product availability is available at:

http://www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/19_probiotics

_prebiotics.pdf