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5 Articles in this Series
Introduction
Are Opioids Being Overprescribed For Fibromyalgia?
Low Back Pain Exercise Tips
Opioid-Induced Constipation: Why Are Clinicians Uncomfortable Talking About It?
Quantum Theory vs Medications to Treat Peripheral Neuropathy
You Are Your Microbiome

You Are Your Microbiome

In a keynote address at the annual clinical meeting of the American Academy of Pain Management, Donald C. Manning, MD, PhD, discussed the important diagnostic and therapeutic possibilities of the microbiome—“the sum total of all microbial genomes in and on the body.”1 The genetic make-up of the gut microbiome alone is approximately 150 times that of the human genome, Dr. Manning said, adding that the body can be considered a “super-organism” including all the human and microbial genomes working as an interacting whole.

A person’s microbiota (the population of microorganisms containing the microbiome) develops from birth (initial colonization) through adulthood and is affected by mode of delivery (vaginal vs. Caesarean-section), environment, diet, hygiene, and where you live (urban vs. rural area). “The gut microbiota is a dynamic ecosystem,” said Dr. Manning, the Chief Medical Officer at San Francisco-based Adynxx, Inc. and Clinical Associate Professor of Anesthesiology at The University of Virginia.

“The role of the gut microbiota is diverse,” he said, noting that it plays a protective role against pathogens and is involved in metabolism of nutrients, lipids, bile acids, and dietary fibers. But the gut microbiota also acts to promote the gut barrier (not allowing pathogens in) and modulates intestinal motility, Dr. Manning said. In addition, the microbiota aids in brain development and modulation of behavior, including visceral sensory reflexes as well as social, emotional, and anxiety-like behaviors. Loss of microbiota diversity in the gut, called dysbiosis, can lead to gastrointestinal (GI) disorders such as irritable bowel disease, as well as skin disease, obesity, allergies, autoimmune disorders, cancer, pain, and behavioral disorders (depression, anxiety).

Perhaps the biggest cause of the loss of gut microbiota diversity has been the rise in the use of antibiotics, both in therapeutic doses, as well as at subtherapeutic doses found in the food supply. The “use of antibiotics early in childhood can result in a disordered hypothalamus-pituitary-adrenal axis,” Dr. Manning said. In fact, it can take up to 1 year to restore the diverse flora lost as the result of 1 course of antibiotics, he added. Extended use of antibiotics can lead to severe dysbiosis and dangerous overgrowth of Clostridium difficile, leading to chronic diarrhea. On a positive note, fecal transplants have been shown to be highly effective at restoring the microbiota to a normal healthy state.2

The microbiome also is affected by stress. Stress can increase the levels of norepinephrine and epinephrine that can activate receptors on the gut microorganisms activating toxicity properties. Certain bacteria can break down nutrients into metabolites such as propionate, butyrate, g-aminobutyric acid, and serotonin.

Microbiome-Pain Connection

It has been shown that a healthy gut with a diverse microbiome is essential for the development of a normal inflammatory pain response, Dr. Manning noted. If the GI system is populated with the wrong bacteria, there is an increase in pro-inflammatory cytokines and the development of visceral hyperalgesia. In fact, dysbiosis due to oral antibiotics has been associated with hypersensitivity to colonic distension.

Probiotic therapy has been shown to treat visceral hyperalgesia. For example, Lactobacilli acidophilus NCFM modulates intestinal pain and activates opioid and cannabinoid receptors. In addition, according to Dr. Manning, L. reuteri prevents colonic hyperexcitability and L. plantarum inhibits inflammatory distention and pain. Probiotic use has been reported to reduce anxiety and stress response, and improve mood in patients with irritable bowel syndrome and chronic fatigue syndrome. Tillisch et al has shown that consumption of a fermented milk product containing specific probiotics modulates brain activity affecting midbrain connectivity.3

“Not all probiotics are active,” he cautioned, “and it very much depends upon the specific strain of probiotic organism used. Probiotics may help, but researchers are nowhere near knowing which ones help and which do not.”

How does this all relate to pain management? “The complexity of the superorganism helps us explain the variety of physical and emotional aspects of pain. We are about to enter an even more advanced level of diagnosis and therapy with the application of pharmacometabolomics,” he said. Pharmacometabolomics is the study of how drugs are metabolized based on an individual’s total genome, gut microflora, environment, etc. “Ideally, therapy could be targeted based in part on an individual’s microbiome.” Dr. Manning concluded that this may lead to a “bottom-up” approach to treatment, paying attention to microbiome-related changes in behavior and pain.

Dr. Manning has disclosed that has ownership interest in Adynxx, Inc.

Reported by Nikki Kean

References

1. Manning DC. Emerging role of the microbiome in pain medicine. Presented at: American Academy of Pain Management. Phoenix, Arizona, September 18-21, 2014.

2. Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312(17):1772-1778.

3. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144(7):1394-1401.

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