Fibromyalgia, Irritable Bowel Syndrome And Endotoxemia
Fibromyalgia is a disease characterized by chronic wide-spread pain. These painful areas are spread throughout numerous points on the body. Other symptoms of this disorder are joint stiffness, gastrointestinal upset and mental distress: insomnia, fatigue, depression, anxiety, and cognitive dysfunction.
Estimates for the prevalence of fibromyalgia range from between 1% to 2% of the population. And of this population, women far outnumber men.
The black dots in this graphic illustrate the common areas many sufferers report as tender or painful. The combination of widespread pain along with assessment of cognitive distress is the standard method used by physicians to diagnose it.
Current treatment options include, although are not limited to, medications to lessen pain, antidepressants, cognitive behavior therapy and exercise. What is not a common treatment option is the use of prebiotics and probiotics, which in my humble opinion, is a huge oversight.
While the role of endotoxemia and fibromyalgia may have escaped the notice of many health-care practitioners, it’s as clear as daylight to me. The reason I say this is because of a 2004 study conducted at Cedars-Sinai Medical Center in Los Angeles. (1)
I mentioned this study in part two of my small intestinal bacterial overgrowth (SIBO) series. Today I want to give this study a bit more attention.
The common association of gastrointestinal distress and fibromyalgia is well-known. An estimated 32% of patients with fibromyalgia are diagnosed with irritable bowel syndrome (IBS). 81% report irregular bowel habits. (2)
While the prevalence of SIBO in IBS sufferers is well documented, these researchers were curious to discover if SIBO is common in those with fibromyalgia.
Forty-two fibromyalgia patients were recruited from the rheumatology practice group of Cedars-Sinai Medical Center for this study. Another 111 volunteers with IBS were also asked to take part. Fifteen people presenting with neither fibromyalgia nor IBS served as controls.
Persons were excluded from this study if they met any of the following criteria: antibiotic use within the previous three months, previous screening for SIBO, history of diabetes, thyroid disease, intestinal surgery other than removal of the gallbladder or appendix, connective tissue disease, use of narcotics, gastrointestinal disease other than IBS, renal insufficiency, or probiotic use.
After an overnight fast, all subjects were given a drink containing lactulose. As you may recall, lactulose is an indigestible sugar. As such it should reach the colon intact where it is set upon by colonic bacteria and fermented into either methane or hydrogen gas. This test, by the way, is called a lactulose breath test (LBT).
Peak measurement of methane or hydrogen registers just once in a healthy individual. In someone with SIBO, however, bacterial overgrowth from pathogens typically migrating from the colon into the small intestine also leads to fermentation and gas production in that part of the digestive tract. Therefore, if the LBT records two separate methane/hydrogen peaks, SIBO is suspected.
As I’ve mentioned in the past, there are many false negatives with this test. It is quite possible that digestive transit time is so fast–for example in diarrhea–that the test fails to detect SIBO. It’s why a good clinician doesn’t solely rely on the outcome of a breath test to diagnose small intestinal bacterial overgrowth.
Here we see the results of the LBT in the different groups studied. Of the 15 “normal” controls, three tested positive for SIBO, hence my use of quotes around the word normal.
Of the 111 IBS volunteers, 93 or 84% registered a positive test result. My guess is that the other 16% were misdiagnosed due to rapid transit time or were undiagnosed celiacs or sensitive to gluten. (3)
Of the 42 fibromyalgia patients, 100% were positive for SIBO. Yes, you read that right. All of them had SIBO.
Here we see illustrated the combined hydrogen breath excretion of both the IBS (diamonds) and fibromyalgia study participants (squares). The difference in hydrogen excretion after the first hour is significant.
Of the 42 fibromyalgia patients, 41 had enough historical data to allow a medical diagnosis of IBS. Of these 41 patients, 22 or 54% met this criteria.
Finally, among these patients, there was a significant correlation between the level of pain reported and the peak level of hydrogen gas.
In the discussion section of this paper, the researchers mention a rodent study that found that E. coli caused globalized hyper-pain responses in these animals. (4) This doesn’t surprise me as E. coli is a gram-negative pathogen.
For those of you visiting this blog for the first time, please read my post on how lipopolysaccharides (LPSs) derived from gram-negative bacteria can lead to inflammatory-immune responses and disease when crossing the gut wall. You can find it here.
The ability of LPSs to induce pain in healthy humans has been recently confirmed. (5) In this study, eleven healthy men were injected with a solution of LPS and assessed for the perception of visceral pain.
As expected, cytokine levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were higher in these subjects. Of the two cytokines measured, pain perception was directly correlated with levels of IL-6.
Why there is a difference between the manifestation of pain between IBS sufferers with SIBO and persons presenting with fibromyalgia is still a mystery. It’s possible that those presenting with IBS are more sensitive to LPS-induced pain signals in their gut, yet less sensitive to these signals elsewhere in their bodies.
However, the increased hydrogen production in those with fibromyalgia suggests a more extensive bacterial infection. LPS when in contact with the gut wall always increases intestinal “leakiness”. The more pervasive the infection, the more permeability and the higher the activation of inflammatory cytokines like IL-6.
The differential in fibromyalgia occurrence between sexes is likely due to gender differences in gut flora composition. A very recent paper detailed how gut flora influences testosterone production. (6)
In this study, transferring gut flora from male mice to female mice, increased testosterone levels in the female mice and protected them from developing type 1 diabetes. The increases in testosterone did not, by the way, affect their fertility.
This is an amazing finding considering that the mice used in this study have a genetic predisposition to developing type 1 diabetes. Another illustration that genes are not destiny.
Since autoimmune disorders are typically more common in women than men, this discovery of hormonal regulation by microbial gut communities is groundbreaking.
The microbiome of women, coupled with environmental factors (puberty, pregnancy, diet, stress, birth control, antibiotic use, licit and illicit drug use, infections, etc.), affect hormonal levels. This has important implications for unraveling the mysteries of autoimmune disease, breast cancer and the incidence of chronic disorders like fibromyalgia.
If you have fibromyalgia, I strongly recommend you schedule an appointment with a gastroenterologist to screen for SIBO. My series on SIBO will provide you with lots of information in the meantime. Part one can be found here.
I strongly caution against the use of non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen to treat your pain and discomfort. I fully recognize that doing so may aggravate your symptoms. However, the well-documented negative effect these types of analgesics have on gut barrier function is the last thing you need when confronting a severe case of endotoxemia.
A survey of fibromyalgia patients rated NSAIDs more effective than acetaminophen in relieving their pain and hinted at their widespread use in this population. (7) The long-term consequences of using these drugs, however, are clearly self-defeating when intestinal “leakiness” is suspected.
While the use of non-NSAID tramadol has been found effective in managing pain, reports of its constipating side-effects concern me greatly. This isn’t surprising as this drug works on opioid receptors, including those in the gut.
Constipation exacerbates endotoxemia. Peristalsis not only propels partially digested food and feces along, it also serves a vitally important housekeeping function by preventing pathogens from attaching to and breaching the gut wall. Once peristalsis is compromised, the risk of gram-negative bacteria entering the portal vein to the liver and translocating to systemic circulation increases.
Also recall that impaired peristalsis is the number one reason colonic gram-negative pathogens are able to migrate to the small intestine. Opioids, including those formed by the partial digestion of gluten or A1 beta-casein, always impact peristalsis for the worse.
The dysbiosis at the heart of fibromyalgia, not to mention IBS, cannot be overcome without clearing up the infection and repopulating the gut with beneficial flora. Anything less will guarantee the persistence of these conditions.