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The Hyperpermeable Bowel

In addition to its very important functions of digestion and absorption, the gastrointestinal tract is also the largest organ of the immune system in the body. The percentage of lymphocytes residing in the GI tract are estimated to range between 60% to 80%.

When we eat, we want the digestive system to absorb all the good stuff while keeping out all the potentially toxic, antigenic and pathogenic materials in food. How can the digestive system possess the innate intelligence to exclude noxious materials while allowing for the entry of nutrients? The answer lies in the four levels of protection provided by the barrier system of the GI mucosal wall:

1. Mucus layer covering the microvilli
2. Tight junctions between epithelial cells
3. GALT-sIgA in the mucus of the glycocalyx
4. Probiotic species

The GIT (gastrointestinal tract) has the greatest amount of surface area exposed to the environment of all three barrier systems in the body. In humans, the skin has less than ten square meters of surface area, whereas the lungs have about 140 square meters. The human gastrointestinal tract, however, has 320 square meters of surface area exposed to the environment. These surface area relationships are comparable in veterinary species as well.

Disturbances to the GI mucosal barrier
The GI mucosal barrier can be disturbed by factors associated with GIT injury, exposure to toxins or infection. Bacterial infections and endotoxins can injure the tight junctions holding intestinal mucosal cells together.

Bacterial overgrowth secondary to inappropriate use of H2 blockers and antacids can lead to proximal gut colonization by pathogenic bacteria that are “attracted” to the more alkaline pH. Immunosuppressed or protein-deficient patients can have decreased sIgA production, which impairs the immunoprotective value of this secretory immunoglobulin. sIgA is embedded in the mucus layer (or glycocalyx) that overlies the mucosal epithelia.
The liver provides defensive activity both in terms of its phagocytic Kupffer cells, and its enzyme detoxification systems. The liver has a dual-phase system of detoxification. Hepatic enzymes decontaminate toxins and metabolic toxic by-products, and help degrade antigens and antigen/antibody complexes. Kupffer cells are the sessile hepatic macrophages found in hepatic sinusoids; they play an important role in the GI immune system by removing bacteria, particulate matter and toxins.
Compromised barrier function increases the total toxic load on the body as a whole by allowing ingested toxins and xenobiotics entry into the systemic circulation, bypassing the portal circulation, thus allowing these foreign substances entry into the body without modification by hepatic detoxification enzymes.
Contrary to the recommendations of folk medicine, prolonged fasting may do more harm than good in patients with challenged immune systems. “Bowel rest” for more than three days has been shown to cause deterioration of the enterocyte population, which can lead to atrophy of the mucosal surface, alterations in bowel permeability and an overall diminution of gastrointestinal immune function. Studies have shown that early enteral feeding can improve splanchnic blood flow and immune system function.
With disrupted barrier function, antigens and pathogens are allowed to gain entrance into the systemic immune system. The first contact of antigens and pathogens is with dendritic cells that then carry the information from those antigens or pathogens to naïve B and T cells, and “activate” them to be specific for those antigens or pathogens.

Following their activation, naïve T and B lymphocytes clone themselves and then migrate to the regional mesenteric lymph node. From the regional lymph nodes, these activated lymphocytes enter the lymphatics, and from there the venous circulation and systemic blood supply, ultimately migrating back to a specific anatomical region of the GI tract.

Increased immune mobilization leads to disease
When allergens and pathogens are prevented from being absorbed into the systemic circulation by healthy mucosal barrier mechanisms, there can be no systemic immunological response (Hamilton, 1985). Disrupted bowel barrier function, however, will lead to inappropriate increases in antigen and toxin loads and will disrupt detoxification mechanisms, thereby creating increased immune system and liver enzyme mobilization. Over time, this can lead to chronic pathology. Disrupted bowel barrier function has three synonyms:

1. Hyperpermeable bowel
2. Increased intestinal permeability
3. Leaky gut

Impaired barrier function can also lead to diseases of the immune system. For instance, when bowel permeability increases, classic hypersensitivity to foods and components of normal gut flora can result (Galland, 1993). Bacterial endotoxins, cell wall polymers and dietary gluten may cause non-specific activation of proinflammatory pathways mediated by complement and cytokines. In experimental animals, chronic low grade endotoxemia has been shown to contribute to the development of auto-immune disorders (Branganza, 1983). Increased intestinal permeability may be either involved in the course of each disease, or may be a secondary effect of the hyperpermeability leading to immune activation and hepatic dysfunction, creating a vicious cycle of disease promotion.

Measuring intestinal permeability
The measurement of increased intestinal permeability in veterinary species requires measured urinary collection with a urinary catheter in place. This makes it more difficult to diagnose without hospitalization.

Typically, in the measurement process, different sized, nondigestible long chain sugars are administered orally, and collected in the urine. The ratio of shorter to longer chain sugars defi nes whether the barrier has been breached, which allows increased urinary recovery of longer chain sugars. Thus, unless it is being specifi cally measured, the role of increased intestinal permeability often goes unrecognized. There’s a new and emerging methodology of food sensitivity and intolerance testing that measures food ingredient-specifi c IgA and IgM in the patient’s saliva, serving as a practical, non-invasive screening for increased intestinal permeability. Secretory (mucosal) IgA is lower with a disturbed intestinal barrier mechanism, and this test can help quantitatively measure food-related antibodies directed against IgA and IgM. Preliminary studies suggest this testing methodology yields highly accurate results. The value of the test is not simply as a screen for leaky gut; it will also help substantially with the formulation of hypoallergenic diets (Miller, 2010; Pfaffe, 2011; Swanson, 2003).

The 4Rs
The hyperpermeable bowel can be treated and managed successfully with a four-part treatment program (“The 4Rs”) that uses diet, herbs and nutraceuticals to reverse the causes and risk factors for increased intestinal permeability. Many naturally occurring substances can help repair the intestinal mucosal surface, or help improve hepatic function when it is overwhelmed by an excessive total toxin load (Galland, 1993; Nathens, 1996; functionalmedicine.org).

1 REMOVE pathogens, allergens and toxins. By lowering the “total load” (the body’s burden) of these troublesome substances, the immune system and liver do not need to work as hard in processing them. This makes more energy available to direct toward re-establishing healthy patterns. removal can be done by elimination from the diet or environment, or by the use of agents such as antimicrobial agents to reduce the population of pathogenic organisms.

2 REPLACE digestive factors that are inadequate or absent. inadequate pancreatic or intestinal enzyme production leaves digesta only partially broken down, thus altering the environment in the bowel and providing opportunity for pathology to develop. The benefi cial bacteria that produce short chain fatty acids (SCFA) from soluble fi ber in the bowel need a narrow range of temperatures and pH, as well as adequate substrate for their activity. When food is only partially digested, the intermediate breakdown products of digesta do not promote healthy microfl oral ecology. An example of this is the small intestinal bacterial overgrowth (SiBo) seen with EPi.

3 REPAIR damaged intestinal mucosal barrier. The use of the free form amino acid l-glutamine reduces bacterial translocation, and increases the protein synthesis of enterocytes, enabling them to increase their rate of selfrepair. The phospholipid-rich compound lecithin, and the omega 3 fatty acids commonly found in fi sh oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are also integral to repairing intestinal mucosa damaged from disease, stress, toxins or diet.

4 REINOCULATE with probiotic cultures and accessory nutrients to create healthy bowel ecology. Endogenous and transient probiotic Gi microbial fl ora are extremely important factors in maintaining a healthy Gi mucosal barrier. Anaerobes are the most numerous bacteria in the bowel. These commensal benefi cial microorganisms compete with potential pathogens for nutrients and attachment sites to the mucosa, thereby inhibiting bacterial overgrowth by pathogenic gram negative bacteria. Antibiotics can upset this balance between good and bad bugs. H2 blockers and hyperosmolar enteral diets can result in bacterial overgrowth.

Know About Nutrigenomics

Nutrigenomics is an emerging science that studies the molecular relationships between nutrition and the response of our genes, to determine how even subtle genetic changes can affect human and animal health. The basic concept is that chemical nutrients affect gene expressions in a specifi c mode by switching from health to a pathophysiological condition, or vice versa. Nutrigenomics designs optimal nutrition based on an individual’s unique genotype. Simply stated, nutrigenomics defi nes functional foods based on an individual’s genes.

The role of diet and nutrition continues to be a major focus of study when addressing the increasing incidence and recognition of diet-related diseases in humans and animals. Nutrition research is studying how dietary constituents at the molecular level can optimize and maintain cellular, tissue and organ balance to help prevent disease.

The development of nutrigenomics has been aided by powerful advances in genetic research. Genetic variability, the inter-individual differences in genetics, can affect metabolism as well as an individual’s phenotype. Genetic disorders of nutritional metabolism can cause abnormal physiological effects that are exhibited as population diversity. Simple examples would be the genes associated with obesity or diabetes in various canine species, and vitamin B12 deficiency in giant Schnauzers.

Nutrients relay signals that tell a specific cell in the body about the diet. Basically, a sensory system in the cell interprets information from nutrients about the dietary environment. Once the nutrient interacts with this system, it changes gene (genomics) and protein (proteomics) expression and metabolite production (metabolomics) accordingly. So different diets elicit different patterns of gene and protein expression and metabolite production. Nutrigenomics describes the patterns of these effects, which are called molecular dietary signatures.

An important aim of nutrigenomics involves identifying the markers of early phases of diet-related diseases, so that nutritional intervention can return the patient to a healthy state. Another aim is to demonstrate the effects of biologically active food components on health, leading to the design of functional foods that will keep individuals healthy according to their own specific needs.

Recently, veterinary and nutrition scientists have begun applying animal genomics to the field of nutrition. Nutritional genomics and proteomics will play a vital role in the future of pet foods. Functional genomics will emerge as important areas of study, now that the genome “maps” for the dog are available.

Studying and monitoring the health of dogs parallels that of humans. Close to 500 canine genetic diseases have been described to date. Molecular biological techniques have been used for several decades to identify the cause of single gene disorders in animals, allowing for prevention and treatment strategies. Currently, at least 30 canine disease genes have been cloned and characterized. This has led to the development of genetic mutation-based tests for diagnosis and carrier detection. These tests permit the elimination of carriers from the breeding population, ultimately decreasing or eliminating the incidence of disease.

However, while determining the DNA sequences of single gene mutations is now feasible, identifying the genetic loci (locations on the genome) responsible for complex genetic diseases is a much more difficult task. Nevertheless, dogs serve as excellent models for the nutritional diseases in other animal species and humans. Although a genetic component exists for these conditions, nutrition plays a major role in the development and/ or treatment of many. Changing lifestyles in urban populations have led to a significant increase in obesity and diabetes in people and dogs. The negative health outcomes of obesity and diabetes observed in humans are also seen in canines. These are just two common examples of animal diseases having both a nutritional cause and a therapeutic component.

Certain dietary constituents such as vitamins A and D, zinc and fatty acids can directly influence gene expression, whereas others such as dietary fiber can have an indirect effect through changes in hormonal signaling, mechanical stimuli, or metabolites produced from the microbial flora in the bowel.

So-called “functional” food ingredients and herbal supplements are now being incorporated into animal as well as human foods. Examples of nutrients currently added to pet foods include those intended to improve joint health such as glucosamine, chondroitin sulfate, and green lipped mussel. Others protect the body from cellular free radical damage, and include vitamin E, beta carotene and selenium. Omega-3 fatty acids improve the skin, while oligosaccharides (carbohydrates) and probiotics are good for gut health.

It’s also important to keep in mind that the benefits provided by pet foods designed for a dog’s life stages, body type or lifestyle may be well suited for one dog, but not another. With our growing knowledge of genes and gene expression, it should be possible to formulate diets not only for preventing structural abnormalities, but also for more complex diseases such as diabetes, cancer, aging, behavioral changes and heart disease.

In summary, animal nutrition professionals need to be able to prescribe or recommend nutrients and diet formulations based on a more precise knowledge of how nutrients or food components interact at the level of the genome. Diets for dogs should be designed and tailored to the genome or genomic profile of the individual in order to optimize physiological balance, disease prevention and treatment, and performance. Our advancing knowledge about human and animal genomes, along with the breadth of biotechnology, offer us the opportunity to individualize dietary intervention to help prevent, mitigate or cure chronic diseases.

Toxoplasmosis Causing Concern


A new report released by the Advisory Committee on the Microbiological Safety of Food in the UK recommends more research while confirming information about a disease the US Centers for Disease Control and Prevention consider a “major neglected parasitic infection”.

According to the CDC, toxoplasma gondii, a parasite that infects cats and causes toxoplasmosis, has infected 22.5% of the human population in the US. The CDC lists toxoplasmosis as one of the leading causes of human death attributed to foodborne illness in the US.

While the disease often has no symptoms, it can also cause serious illness and even death in people with an immunodeficiency, such as newborns, people undergoing chemotherapy and AIDS patients, the CDC says.

Toxoplasmosis can be prevented. Advise clients to clean litter boxes at least once a day, and to wash their hands well after scooping feces or handling their cats. Pregnant woman and those with immune-related illnesses should avoid cleaning litter boxes, or wear gloves and a mask when doing so. cdc.gov

Lameness & Saddle Slip


There’s a significant link between hind limb lameness and saddle slip, according to a new study from the Centre for Equine Studies at the Animal Health Trust in the UK. The research shows consistent saddle slip in some horses with hind limb lameness, even when the lameness is fairly subtle and difficult to detect. Saddle slip in sports horses can occur for a variety of reasons, including asymmetry in the shape of the horse’s back, riders sitting crookedly, and ill-fitting saddles.

The study assessed 128 horses of varying size, age and type. The saddle consistently slipped to one side in 54% of horses with hind limb lameness, compared with 4% of horses with fore limb lameness, 0% with back pain and/or sacroiliac joint region pain, and 0% of non-lame horses. Diagnostic analgesia was subsequently used to abolish the hind limb lameness, eliminating saddle slip in 97% of cases.

“Our findings emphasize the need to educate owners, veterinarians, physiotherapists, trainers, riders and saddle fitters that saddle slip is frequently an indicator of lameness, not necessarily a manifestation of an ill-fitting saddle or asymmetric shape of the horse’s back,” says Sue Dyson, Head of Clinical Orthopaedics at the Centre. “Detection of saddle slip provides an opportunity for the owner, riders and trainers to detect low-grade and subclinical lameness.” aht.org.uk

New $80 Million Equine Complex


Equine science education, research and outreach will soon have a new home, thanks to the Texas A&M Equine Complex. Dr. Eleanor Green, Texas A&M College of Veterinary Medicine & Biomedical Sciences’ Carl B. King Dean of Veterinary Medicine, says the initiative will bring together students, faculty and equine industry leaders, and provide a foundation for research discoveries and outreach initiatives dedicated to the welfare of horses.

Initial construction, which has already begun, will include an education and outreach center, facilities for the Texas A&M Equestrian Team, a cross country course in collaboration with Texas A&M Athletics, and new facilities for the Parsons Mounted Cavalry.

With a long history of teaching, research, equine medicine and outreach excellence, Texas A&M has been a vital contributor to the equine industry for generations. Both the Department of Animal Science in the College of Agriculture and Life Sciences and the College of Veterinary Medicine & Biomedical Sciences have been instrumental in providing the equine industry with knowledge and care that have advanced not only equine sciences, but the welfare of the horse as well. TAMUequine.com

Gaining Ground Against Rabies


The Global Alliance for Rabies Control (GARC) has revealed details of their latest initiatives against the disease. The Communities Against Rabies Exposure (CARE) program, led by GARC in collaboration with local governments, universities and research institutes, has received a multi-million dollar grant from the Optimus Foundation in order to expand their successful trial of community-led rabies elimination in Bohol, Philippines to communities in Chad, Indonesia, Tanzania and further areas of the Philippines.

GARC also announced a grant from the Bill & Melinda Gates Foundation for the development and promotion of Partners for Rabies Prevention activities, including the development of health economic models and a global rabies elimination plan. These plans will be formed in collaboration with leading PRP players, including the WHO, CDC (USA) and a number of universities, and will bring together expertise from a variety of fi elds to provide much-needed research to help inform and advance policy decisions. rabiescontrol.net

Mobile ECG Device


The developer of a breakthrough mobile electrocardiogram (ECG) recorder that attaches to an iPhone or iPod Touch has made its mobile ECG device available to veterinary professionals. The AliveCor Veterinary Heart Monitor snaps onto an iPhone 4, 4S or iPod touch, and when used with the free AliveECG Vet app, enables veterinarians and technicians to obtain clinical quality, singlechannel ECGs on animals.

The Veterinary Heart Monitor enables veterinary professionals to easily screen patients during health and wellness exams, or before placing a patient under anesthesia. Veterinarians can obtain accurate ECG readings, and store them in a secure AliveCor account on the phone and on the web. They can also e-mail and print PDF versions of stored ECGs as part of the medical record or to send to a specialist or colleague. AliveCorVet.com

Cancer Vaccine In Clinical Trials


Specialists from the Veterinary Specialty Center of the Hudson Valley in New York are conducting a pilot study with a cancer vaccine that may prolong survival in dogs with osteosarcoma (bone cancer) and cats with mammary (breast) cancer. The study will test whether an adenovirus-based vaccine followed by a DNA plasmid administered via electrogenetransfer can elicit anti-tumor immunity and increase survival times.

The vaccine targets this Her2/neu pathway of tumorigenesis, allowing the body’s immune system to battle the cancer in addition to standard therapies. No placebos are involved and the study is unfunded. This immunotherapy is an extension of the center’s telomerase cancer vaccine that has shown success against canine lymphoma in Europe.

Up to 50% of dogs with osteosarcoma will express the Her2/neu genetic marker. In cats, Her2/neu has been expressed in this cancer and despite surgical removal of the glands, metastasis is common. ncbi.nlm.nih.gov/pubmed/19379209; ncbi.nlm.nih.gov/pubmed/19944791

Reverse Zoonosis


People who get sick with flu may not realize they can pass the virus not only to other humans, but possibly to pets such as cats, dogs and ferrets. This concept, called “reverse zoonosis”, is still poorly understood but has raised concern among some scientists and veterinarians.

Veterinary researchers at Oregon State University and Iowa State University are working to fi nd more cases of this type of disease transmission and better understand any risks they pose to people and pets.

“We worry a lot about zoonoses, the transmission of diseases from animals to people,” says Christiane Loehr, an associate professor in the OSU College of Veterinary Medicine. “But most people don’t realize that humans can also pass diseases to animals, and this raises questions and concerns about mutations, new viral forms and evolving diseases that may potentially be zoonotic.”

The researchers are surveying fl u transmission to household cat and dog populations, and suggest that people with infl uenza-like illness distance themselves from their pets. If a pet experiences respiratory disease or other illness following household exposure to someone with the infl uenza-like illness, the scientists encourage them to take the animal to a veterinarian for testing and treatment.http://vetmed.oregonstate.edu or http://vetmed.iastate.edu.

Toxic Treats From China


Here’s a good reason to give your patients only healthy, natural, domestically made treats. According to Wenonah Hauter, Executive Director for Food & Water Watch, thousands of dogs have fallen ill or died over the past fi ve years after eating jerky treats made in China.

“…it has come to light that Chinese government offi cials overseeing the factories that make the questionable treats refused to allow US inspectors to collect samples for independent analysis,” she says. “While this lack of cooperation shows an unfortunate disregard for health and safety on behalf of the Chinese government, it’s the Food and Drug Administration (FDA) who has shirked its responsibility to keep US citizens and their pets safe…. The FDA waited until it received 2,000 reports of illnesses and deaths in US dogs before launching its investigation. Although the China investigation took place in April of 2012, it took the FDA four months to admit that they were denied permission from collecting samples from the Chinese facilities. As the FDA dragged its feet, the suspect treats remained on store shelves and put thousands of dogs at risk.” foodandwaterwatch.org