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What is the Microbiome?

This is the assortment of non-human microbial cells in or on the human body (most commonly associated with the gut).  This is not just bacteria but also viruses, archaea, protozoa and fungi.

There are 10x the number of microbial cells in the human gut than human cells in the whole human body, totaling roughly 100 trillion microbes representing as many as 5,000 different species and weighing approximately 4 pounds1.


The microbiome is involved in harvesting energy from food, manufacturing neurotransmitters, enzymes and vitamins and are involved with immune and metabolic functions.  Hence, the microbiome plays an essential role in our overall health.  Having a grand variety of different microbes in the gut correlates with better health than having only a select few bugs. Aging is associated with decreasing microbial diversity and the reduced diversity correlates with compromised nutritional status, increased inflammation and frailty.  Gut microbiota also differ in obese individuals versus lean individuals, and those with atherosclerosis, diabetes, and metabolic syndrome.


How Does The Microbiome Affect Neuropathy?

There is no proven mechanism in which our microbiome causes and/or contributes to neuropathy, however, there are many theories2!

  1. It’s postulated that an unhealthy microbiome can alter the balance of inter and intra cellular Calcium leading to greater activation of the nociceptors (neurons that carry pain signals).  
  2. Alpha-hemolysin is a pore-forming toxin secreted by Staphylococcus Aureus and is one of a multitude of bacterial secreted molecules that could cause spontaneous pain.  
  3. Viral and fungal pathogens have been shown to alter pain sensitivity by the way they stimulate the immune response.
  4. 90% of the neurotransmitter serotonin is produced in the gut, which affects how we manage and perceive pain signals.  Other major neurotransmitters Gamma Amino Butyric Acid and Glutamate which influence our pain perception are also produced by bacteria in the gut.  Hence problems with the microbiome can alter the levels of neurotransmitters in our body leading to more pain.
  5. Microglia (immune cells in the spinal cord/brain) are compromised and change structure with a lack of varied microbiota but can return to proper structure with the recolonization of varied microbiota.  Altering these immune cells in the nervous system via the microbiome can affect our pain perception.
  6. Many hormones in the body are created in our intestines, some in particular such as Glucoagon-like Peptide and Neuropeptide Y are involved in pain modulation.  The production of these hormones can be altered by the microbiome.
  7. Problems with the microbiome can also lead to the release of pro-inflammatory Cytokines which are proteins that alter cell functioning which can lead to neuroinflammation.

Overall, the gut microbiome is the main intersection of immune, neural, endocrine and metabolic signaling.  Hence improving the state of our microbiome can have far reaching benefits to our nerves and the rest of our body.

So What Should Someone With Neuropathy Do About Their Microbiome?

EVERYONE WITH PN NEEDS TO EAT A HEALTHY DIET!  For a healthy nervous system, for a healthy microbiome, to help ensure a healthy weight w/ less pressure on your feet, to give yourself more energy so you can exercise and so you feel better!!!!

What diet???  There are many nuances that should be customized to the individual but I highly recommend the Autoimmune Protocol as a starting point for most people with PN.  Here is a link explaining what is permissible and what is not permissible on the diet.  To sum up the diet though, it cuts out all foods that are known to potentially disrupt the microbiome or immune system and emphasizes foods that promote a healthy microbiome / immune system.  While staying within the confines of what is permissible in the AIP diet is important, it’s also very important to have a great variety of the different plant based foods within the AIP.  Striving to have at least 40 different species of plants, including spices and herbs, per week helps grow a greater variety of microbiota.

Fasting: In addition to what you eat, when you eat matters too.  A study done on people who fasted (only drank water) for a week showed decreased amounts of Fusobacterium3, which is a bacteria associated with colorectal cancer.  I have not come across any research done on fasting and its impact on neuropathy but there is research showing caloric restriction can help improve neuropathic pain.  Fasting is presumed to help reduce the ‘bad’ bacteria in the gut and then when a person begins eating again (assuming they eat foods within the AIP) they can now grow more of the ‘good’ bacteria in the absence of the ‘bad’ bacteria.

Fecal microbiome testing: You can send in stool samples to companies that will do a lab workup on it and let you know the state of the microbes existing in your intestines.  This allows you to find out how varied your microbiome is.  This information may not be a very beneficial testing procedure to jump right into, because if you already know you’re not healthy; you can probably assume you don’t have a healthy microbiome.  However, if you have already tried the AIP diet and fasting without any improvements, this may be a good option to try.  Plus, along with the reports, the companies will also provide a customized set of recommended probiotic supplements as well as specific foods to eat and not to eat based on the results.

There are a variety of companies that provide this service and after researching several of them, I found Sun Genomics to be the best.  They use the more up to date ‘Whole Genome Sequencing’ which detects more microbes with greater specificity than the 16s sequencing, they have tested to make sure their probiotics survive the acidic environment of the stomach so they can actually colonize your intestines, and they offer phone support for any questions you have before or after testing.  You can use the promo code DRCAIN25 to save $25.

Probiotics and/or Prebiotics:  Probiotics are living strains of bacteria that add to the population of good bacteria in your digestive system.  Prebiotics are specialized plant fiber that acts as food for the good bacteria. This stimulates growth among the preexisting good bacteria.  You can get these products from fermented foods such as Kombucha, sauerkraut and fermented veggies like carrots or beets.  As in most cases, I recommend emphasizing these whole food products first.  While some studies have reported beneficial effects in supplements, most probiotic products that are commercially available to consumers have not been investigated for effectiveness. Furthermore, there are no standard formulas or dosages.  The best chance at getting probiotic or prebiotic supplements that will be helpful is to do the fecal microbiota testing first and then get the recommendations specific to you from the personnel that specialize in this field.

Fecal Microbiota Transplant is a treatment that dates back over 1000 years to Chinese practitioners and was first published as a modern therapeutic intervention in 1958.  It is the process by which a fecal sample from a “healthy” individual is transplanted into the gut via enema, nasogastric tube or colonoscopy of a diseased patient. The goal is to inoculate the patient with the ‘healthy’ bacteria that may have previously gone extinct.  It has been the most successful treatment for patients with antibiotic resistant C. difficile thus far4.  It has demonstrated a 92% success rate across early studies.  It’s even been used in horses to help with diarrhea and other gastrointestinal problems.

There was a recent case study done on a lady who has had chronic Diabetic PN  She had tried ‘everything under the sun’ with no success.  After two fecal transplants within one month her pain had mostly gone away and she no longer needed any pain killer medications5.  Her blood sugar levels also dropped and became more stable!  To date this is the only research I’ve seen showing improvements in humans with neuropathy treated with fecal transplant.  This therapy has also been shown to help with other neurological disorders such as Autism Spectrum Disorder, Multiple Sclerosis and Parkinson’s.  Again, if the AIP diet combined with regular exercise isn’t helping, it would be worth discussing with your doctor trying a Fecal Microbiota Transplant.


These are some of the new emerging therapies and testing procedures related to improving the microbiome.  Furthermore, other healthy lifestyle factors such as exercise, stress management and getting good sleep are all conducive to a healthy microbiome as well.  Taking a holistic approach and ‘leaving no stone unturned’ will surely yield the best results.  


  1. Ferranti et al.  20 Things You Didn’t Know About the Human gut Microbiome  J Cardiovasc Nurs. 2014 Nov-Dec; 29(6): 479–481.
  2. Ran Guo et al.  Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential.  British Journal of Anaesthesia.  Vol. 123, 5, Nov 2019, 637-54
  3.  Yan He et al.  Fasting challenges human gut microbiome resilience and reduces Fusobacterium.  Medicine in Microecology Volumes 1–2, 15 December 2019
  4. Brandt.  Fecal Transplantation for the Treatment of Clostridium difficile Infection.  Gastroenterol Hepatol (N Y). 2012 Mar; 8(3): 191–194.
  5. Ting-ting et al.  Fecal microbiota transplantation relieve painful diabetic neuropathy.  Medicine (Baltimore). 2018 Dec; 97(50): e13543.