The Microbiome, Probiotics, and Fecal Transplant Maureen McMichael, DVM, M.Ed., DACVECC
College of Veterinary Medicine Auburn University, Auburn, AL
“Death begins in the colon” Elie Mechnikov 1845-1916
The Microbiome
The microbiome is now known to be an essential player in health and disease. Microbes, chiefly from the gastrointestinal tract, are critical players in immune function, vitamin production, utilization of nutrients, detoxification, inflammatory and autoimmune disorders, and neurotransmission among others. There are separate microbiome
communities on the skin, in the oral cavity, the nasal cavity, the lungs and in most of the body. In 2008 the NIH launched the human microbiome project and a plethora of new research is highlighting the importance of the maintenance of balance in the 100 trillion microbes residing on and in the mammalian body. In 2014 the National Institutes of Mental Health funded research on the microbiome-brain connection (the gut-brain axis).
Cutting edge treatment options include probiotic enemas, fecal capsules and fecal microbial transplants (FMT) and these are being used for infectious diarrhea (C difficile), autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn's disease) and obesity. The Harvard Medical School teamed up with MIT to create the Open Biome Project to make FMT more widely available. This talk will cover essential aspects of the microbiome, with a focus on the gut microbiome, in health and disease. The 2nd half will cover current uses for probiotic enemas, fecal capsules and FMT.
There are at least 4 current clinical trials at veterinary colleges in the US evaluating fecal transplants in various diseases in pets.
Normal GI Flora Formation
It is not clear exactly when the GI flora begins to be formed. New research suggests that it likely starts to be formed during development (via placental transmission of microbes) and is boosted significantly at birth (via vaginal and perianal flora).
There are ~100 trillion micro-organisms in the human gastrointestinal tract, approximately 10 times more than the number of human cells. Micro-organisms are thought to contain 150 times more genes than the human genome. The gut microbiome consists of bacteria, viruses, yeast and protozoa, as well as parasites. Since roughly half of the weight of feces is bacteria the focus of the gut microbiome is primarily bacterial.
The Role of Healthy Flora
The gut associated lymphoid tissue (GALT) is the arm of the immune system residing in the gut. The GALT makes up ~80% of the total immune system! The GALT is responsible for detoxification – a big job since most of the foreign substances we are exposed to occur in the gut. The GI flora is responsible for protecting the epithelial lining (of the GI tract) from pathogen invasion, it modifies the immune system, and it produces neurotransmitters. It is also responsible for production of some vitamins that are essential for health.
The vagus nerve (cranial nerve X) is the longest of the cranial nerves and is the primary communicator between the central nervous system and the GALT. The gut
bacteria communicate with the vagus nerve to send signals to the CNS and the CNS communicates with the GALT via the vagus nerve. The new term for this is the gut-brain-gut axis to highlight the two way street.
Disruptions to Healthy Flora
Up to 90% of human illnesses are associated with a dysfunctional microbiome. Abundant research has shown that C-section (in humans) births are associated with the formation of a significantly different gastrointestinal flora compared with vaginal births. The abnormal flora is associated with a higher incidence of asthma, ADHD, diabetes and a host of other conditions.
After birth, disruptions to the microbiome occur with antibiotic usage – particularly during the vulnerable period of formation (the first months of life). Antibiotics are extremely common – with 4 of 5 Americans taking at least one prescription per year. An association has been made between obesity and antibiotic usage in humans, which is thought to be due to alteration of the microbiome. It has been known for many years that feeding livestock antibiotics increases weight gain.
Dysfunction of the microbiome can also occur with various foods, steroids, environmental influences and, especially, chlorinated water.
Dysfunctional Microbiome and Disease
The most visible colonic microbial abnormality is Clostridium difficile (C. diff), a strain of bacteria that is responsible for severe diarrhea, particularly in the elderly. The resistant forms (resistant to multiple antibiotics) are associated with 14,000 deaths per
year in the US alone. As it has become more resistant to antibiotics (there are many strains that are resistant to all known antibiotics including vancomycin) the death toll has increased. C. diff has recently been completely cured with fecal microbial transplants (FMT) and this is now an approved treatment for C. diff in the US. Antibiotic resistance is a major health threat in the US and 2 million drug resistant infections are reported each year.
A study reported in Nature in 2012 demonstrated that people with type II diabetes had imbalances in their gut microbiome. A study in mice showed that transplanting the normal microbiome to a diabetic mouse seemed to cure the diabetes.
Neurological diseases of many types have been associated with a dysfunctional microbiome. A critical protein (brain derived neurotrophic factor; BDNF) for neuron formation and protection, is produced by the microbiome. This protein has been reported to be low in epilepsy, Alzheimer’s, OCD and depression. The gut bacteria are responsible for secreting GABA (a neurotransmitter that calms down the CNS) and keeping anxiety low. They also secrete glutamate, which is essential for cognition and learning.
The bacteria that line the epithelium of the GI tract are responsible for keeping the junctions tight between cells and preventing leaky gut syndrome. Leaky gut is associated with numerous diseases in people including diabetes, autoimmune diseases, asthma, skin diseases, and Alzheimer’s disease. Another protein, gliadin (the protein present in gluten) can also cause leaky gut as well as leaky blood brain barrier.
In 2004 the Journal of the American Medical Association reported a significant correlation between antibiotic usage and cancer in humans. The use of antibiotics was
associated with an increased incidence and increased death from breast cancer in women. A 2013 report in Nature documented how the microbiome can prevent or promote cancer.
There are two main groups of bacterial organisms that are the most studied. Firmicutes are considered fat lovers since this group increases fat absorption and is more prevalent in obese individuals. Bacteriodetes are more prevalent in lean people and the firmicutes to bacteriodetes (F/B) ratio can determine a person’s risk for several disease conditions such as cardiovascular disease, obesity and diabetes.
Treatment Options
Treatment options range from diet change, probiotic supplements, probiotic enemas, and fecal treatments.
Diet Change
Feeding the pet a diet rich in probiotics is a great start. Traditional cultures use fermented foods to supplement their diets and many pets will eat these readily. It is important to use foods that are healthy and not full of sugar (e.g., yogurt). Sauerkraut, Kim Chi, Kefir, Tempeh, certain pickles, and kombucha tea are all options that can be offered in very small amounts to start.
Pre-biotic foods are non-digestible foods that feed the bacteria. These include raw asparagus, raw jicama, raw onion & garlic (not cats, very small amounts for dogs), raw dandelion greens.
Filtering the drinking water is a great way to stop disruption (the chlorine in the tap water destroys the microbiome daily).
Probiotic Supplements
The two strains recommended include Lactobacillus spp. (small intestines) and Bifidobacterum spp. (colon) The most common strains recommended are L acidophilus, L plantarum, L brevis, and B lactis, B longum.
Probiotic Enemas
These are simple retention enemas using a mixture of 6-8 probiotic (mostly Bifidobacterium spp) capsules mixed (opened up and emptied) with non-tap water (distilled is best). These can be performed once per week for chronic cases or once per day for more acute illness.
Fecal Microbial Transplant
This is the treatment of the future and the use of FMT for gastrointestinal as well as non-GI related diseases such as autoimmune conditions, autism spectrum disorder, and obesity will be discussed. An update on current recommendations in human and
