Leaky Gut Syndrome Revisited

Recently, we have seen a significant increase in research on gut bacteria (known as the microbiome or microbiota) in humans as well as in our companion animals and equine partners.

Several years ago, I wrote an article on the new research of the intestinal system bacterial populations links with inflammation and functions of other bodily systems. The article reviewed what was known then about “leaky gut syndrome” and dysbiosis. Recently, we have seen a significant increase in research on gut bacteria (known as the microbiome or microbiota) in humans as well as in our companion animals and equine partners.  While the causes and effects of gastrointestinal (GI) bacterial imbalance are more understood and appreciated, new research raises more questions.

Leaky Gut and Dysbiosis

At one point we thought that leaky gut and dysbiosis were the same. Now it is understood that leaky gut,  or increased intestinal permeability is one result of dysbiosis. Dysbiosis is defined as an unhealthy change in the normal bacterial balance and ecology of a part of the body such as the intestines, reproductive system, skin, or mouth. With the increased use of genotyping for bacterial identification, researchers have a better understanding of normal populations for humans, dogs, cats, cattle, and horses, and how populations alter with the loss of normal health. Increasingly, new research is indicating that more chronic diseases are related to the alteration of normal bacterial populations, especially of the GI system.  The increased identification of different bacterial and fungal genetic material as normal, symbiotic residents of mammalian bodies has resulted in the current thinking that these other living helpers actually should be treated as a separate organ. When the amount of DNA of these microbes in a normal, healthy adult human is determined, it is more than the DNA of the host.

In the horse, there are several studies to determine not only what are the normal numbers and populations of hindgut bacteria in a healthy horse, but also how those populations shift in the presence of laminitis, colitis, insulin resistance, dietary changes, normal exercise, and transportation.  Healthy horses have diverse populations of bacteria. The majority of gut bacteria comes from the Firmicutes family (including the [Lacto] Bacilli, Staphylococcus and Clostridia bacteria) and the Verrucomicrobia family (common soil bacteria). The rest of the healthy equine hindgut bacteria are comprised of Bacteroidetes (responsible for breakdown of carbohydrates and sugars), Proteobacteria, and spirochetes.  In the small intestines, there are limited studies on normal bacterial populations and what makes a healthy environment for microbes.

Understanding Bacterial Diversity

Bacterial population diversity and numbers seem more sensitive to dietary, health and environmental factors than previously thought.  Horses with diarrhea had less overall bacterial diversity than those without. While Clostridium difficile (C. difficile) can appear in horses with diarrhea, it appears to be a transient interloper, unlike in humans and companion animals.  Horses with chronic laminitis, surprisingly, had a more diverse intestinal microbiome environment than those without. However, even though the bacteria were more diverse, this is due to the increase in microbes that are normally thought to exist in small numbers, and are considered pathogens (disease-causing) when their populations grow. In horses with chronic laminitis, there were increased amounts of Clostridial and Streptococcal bacteria with a decrease in the numbers of the predominant normal flora. Of note, it has been established that a key player in laminitis is a toxin created by the bacterium Streptococcus bovis.  Pregnant mares have different gut bacteria than non-pregnant ones, although the total number seems to stay the same.  Horses with colitis have LESS Clostridial bacteria than normal horses.  In horses with IR (insulin resistance), there is a swing towards a greater number of carbohydrate responsive Verrucomicrobia, a trend also seen in humans with diabetes.  The delicate balance of all residents of the equine hind gut and their responsibilities for maintaining health is complex.This balance of the gut microbiota population is responsible for health of not only the digestive tract itself, but also in a way that reaches far beyond the intestines, making “Leaky Gut Syndrome” a body-wide source of problems.

Aspects of Normal Gut Health

Eighty percent of the lymphatic system, the most important component of the immune system, is associated with the digestive system. Food entering the digestive system is one of the most important ways that toxins are introduced into the body. Added to the normal amount in food, other toxins that can occur include:

  • Toxins from pathogenic bacteria
  • Toxins from the liver’s normal job of breaking down old and dead tissue
  • Toxins from recycling red blood cells and detoxifying the body, which get dumped into bile and thus into the digestive system
  • Toxins from waste from normal metabolism of our cells, including healthy symbiotic bacteria

It’s a pretty amazing system, but also one that’s not entirely sterile and clean. So unless the rest of the body is walled off and protected from it, exposure could (and does) lead to disease.  As the old engineering joke goes, “God must have been a civil engineer because who else would put a toxic waste dump in the middle of a clean recreational area?” (Apologies to any civil engineers!)

The protection of the surrounding lymphatic tissue is only one of the defenses that the body uses to make sure the rest of “recreational area” doesn’t get overwhelmed by the bacteria and toxins in the digestive system. The first level of defense comes from healthy microbes in the intestines. Much like the use of microbes to gobble up oil spills in the ocean, gut microbes can consume and metabolize metabolic and food toxins. Next, there is the normal pH (acidity-alkalinity) of any particular part of the gut and the digestive enzymes that break down various types of chemicals. And last, but not least, the cells that line the digestive system from the stomach to the outlet form a tight and impermeable layer preventing most chemicals from passing unless they are helped with an appropriate receptor (like having a hall pass). Those cells that create that impermeable membrane are kept healthy by living in the proper pH balance and are fed by the waste products of the healthy microbes that are living in the intestines. It’s an efficient system, isn’t it? 

We have known for a long time that disturbances in this tightly regulated and adaptable environment through stress, toxins, bad food, inflammatory flares, changes in pH, and alterations of the normal gut bacterial populations can lead to damage to these gut cells. They atrophy and shrink as a sign of inflammation, thus losing the tight barrier. Gaps appear and those “hall passes” (proper receptors) are no longer necessary for food proteins, toxic substances, inflammatory chemicals, and even bacteria to pass deeper into both blood and lymphatic channels. Eventually, the immune system of the digestive system and then of the entire body can be overwhelmed by the chemicals and inflammation, thus leading to symptoms, even in tissues distant from the gut. This is what is meant by the term, “leaky gut syndrome.”

When my last article on dysbiosis and leaky gut syndrome was published, the mechanisms as to how many of these GI-associated organ symptoms appeared were still unknown.  But now, in many instances, we know that the main mechanism triggered is inflammation. Inflammation provides a normal and critical function that protects the body, however, inflammation is designed to get the job done, then turn off.  A current hot topic in research today is that cancer is considered to be a disease of chronic inflammation—inflammatory processes that have lost an “off switch.”  Recent research on gut microbes and the GI environment has focused on the process of understanding total body inflammation and thus potential sources of cancer.

The Gut-Brain Connection

In addition to cancer, there has now been established in humans, (and suspected in other species), that there is a line from the gut to the brain. A few years ago, it was discovered that certain lymphatic channels in humans went directly from the digestive system to the brain, bypassing the blood-brain barrier. This raises the question that these channels could also be present in animals. Besides this possible hotline for inflammatory-signaling chemicals from gut to brain, digestive system links to the nervous system through the vagus nerve and chemical hormones and neurotransmitters have been found. Signaling to the brain and other parts of the central nervous system has been shown to be disrupted or abnormal when the microbiome is disrupted.

So how does this pertain to our horses?  Many substances present in our horses’ lives—as well as our own—have been discovered to damage the important and healthy balance between the host’s body and these other symbiotic entities living within. It has been known for a while that antibiotics can damage normal, healthy gut bacteria, allowing not only the increased growth of pathogenic bacteria, but also creating a chronic inflammatory state of “leaky gut”.  But steroids, NSAIDs (non-steroidal anti-inflammatory drugs), and certain pesticides and herbicides can also damage gut bacteria  A recent paper published showed that glyphosate (the active ingredient in Round-UpTM) alters gut microbes in rats, leading to an increase in resistant, pathogenic E. coli strains, a decrease in good Lactobacillus bacteria, and liver dysfunction.  Grains that are genetically modified (GMOs) have been shown to contain higher levels of glyphosate residue. Even organic red wines in California and beers in Germany were found to have trace levels or above of glyphosate in them (probably from blow-over or run-off from neighboring farms and vineyards).

Vaccines and Inflammation

Any animal that is already in a chronically inflammatory state can be negatively affected by the immune-stimulating chemicals in vaccines. How often are horses vaccinated without consideration of their other health issues, or put on steroids to minimize a vaccine-induced inflammatory reaction? We also know that gut bacteria in horses and humans can become unbalanced when there is an increase of carbohydrates in the diet. How many metabolic, digestive, and immune problems have been developing in our horses over the past few decades since processed, easily digested and high carbohydrate feeds have entered the market? Let us return to the current issue in the human research world: the link of imbalanced microbiome inflammation to cancer. When I first graduated from vet school, malignant cancers were so rare in horses that the cases were published. Now, some decades later, the studies are about the chemotherapeutics with which to treat the increasing cancers.  The most common malignancy in horses is cancer of the immune system–lymphoma.

Holistic Solutions

What can we do to stop this trend? We need to be more informed caretakers and stewards of not only our horses, but also our environment. Demand that manufacturers test their commercial feed products for harmful residues.  We should not jump to antibiotic usage needlessly, and be mindful of restoring digestive systems with high quality probiotics after they have had necessary antibiotics. We should evaluate the stress on our equine friends during competition season and take steps to minimize inflammation by feeding natural anti-inflammatory nutrients such as omega-3 fatty acids (such as in non-GMO flax), antioxidants (vitamins E, C, A, D), brain food such as B-vitamins, minerals, and electrolytes. We should treat our horses to therapies that have shown to diminish inflammation, such as acupuncture, massage, PEMF, manipulative therapies (chiropractic, osteopathy), herbs, homeopathy, and quiet walks away from noise and hubbub, allowing for grazing on (non-sprayed) grass if possible.  And, most of all, we should educate our friends, fellow competitors, caretakers, trusted veterinarians, and family by sharing all the research and information that we can. When we do this, we make the world better for not only our horses, but also for all of us.

Dr. Kim Henneman, DVM, DACVSMR (EQ, K9), FAAVA, DABT, CVA, CVC, is a longtime contributor to Holistic Horse, and was an early adopter of integrative medical approaches (acupuncture, chiropractic, herbs, homeopathy, nutrition) for horses. Currently, she is the only veterinarian who is board certified in Sports Medicine and Rehabilitation in two species (canine and equine). Her Integrative Sports Medicine and Rehabilitation specialty practice is based in Utah, covers 8 states, and Dr. Henneman treats, lectures to, and provides consultations to animal caregivers throughout the United States, the UK, and Europe when she is not rehabbing and riding her OTQH rescue mare.  To learn more, visit http://www.animalhealthvips.com/home/

REFERENCES:

  1. Costa MC, Arroyo LG et al. Comparison of the fecal microbiota of healthy horses and horses with colitis by high throughput sequencing of the V3-V5 region of the 16S rRNA gene. PLOS One. July 2012; 7(7): e41484.
  2. David LA, Maurice CF et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature Jan 2014; 505(7484): 559-63.
  3. Esteve E, Ricart W & Fernandez-Real JM. Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve with insulin resistance? Curr Opin Clin Nutri Metab Care Sept 2011; 14(5):483-90.
  4. Faubladier C, Chaucheyras-Durand F et al. Effect of transportation on fecal bacterial communities and fermentative activities in horses : impact of Sacchromyces cerevisiae CNCM I-1077 supplementation. J Anim Sci April 2013; 91(4):1736-4
  5. Grimm P, Philippeau C, Julliand V. Faecal parameters as biomarkers of the equine hindgut microbial ecosystem under dietary change. Animal July 2017; 11(7): 1136-114
  6. Julliand V & Grimm P. Horse species symposium: the microbiome of the horse hindgut: history and current knowledge. J Anim Sci June 2016; 94(6): 2262-74.
  7. Leng J, Proudman C et al. Exploration of the fecal microbiota and biomarker discovery in equine grass sickness. J Proteome Res Mar 2018; 17(3): 1120-28.
  8. Lozano VL, Defarge N et al. Sex-dependent impact of Roundup on the rat gut microbiome. Toxicol Rep Dec 2017; 5:96-107.
  9. O’Donnell MM, Harris HMB, et al. The core faecal bacterial microbiome of Irish Thoroughbred racehorses. Letters Appl Microbiol. Dec 2013; 57(6): 492-501. 
  10. Rodriguez C, Taminiau B et al. Faecal microbiota characterization of horses using 16 rdna barcoded pyrosequencing, and carriage rate of clostridium difficile at hospital admission. BMC Microbiology. Sept 2015; 15: 181.
  11. Rosenfeld CS. Gut dysbiosis in animals due to environmental chemical exposures. Frontiers Cell Infection Microbiol Sept 2017; 7:396
  12. Shepherd ML, Swecker WS et al. Characterization of the fecal bacteria communities of forage-fed horses by pyrosequencing of 16S rRNA V4 gene amplicons. FEMS Microbiol Lett. Jan 2012; 326(1):62-8.
  13. Shepherd ML, Ponder MA et al. Fibre digestibility, abundance of faecal bacteria and plasma acetate concentrations in overweight adult mares. J Nutr Sci. May 2014;3:e10.
  14. Steelman SM, Chowdhary BP et al.  Pyrosequencing of 16S rRNA genes in fecal samples reveals high diversity of hindgut microflora in horses and potential links to chronic laminitis. BMC Vet Research; Nov 2012; 8:231.

Weese JS, Holcombe SJ et al. Changes in the faecal microbiota of mares precede the development of post partum colic. Eq

https://holistichorse.com/health-care/leaky-gut-syndrome/See Dr. Henneman's ariticle in Holistic Horse Magazine form 2009