Objectives: Subjects with fibromyalgia (FM) frequently have nonspecific bowel complaints similar to subjects with small intestinal bacterial overgrowth (SIBO). The aim of this study was to test whether 1) SIBO is prevalent in FM, and 2) If treatment of SIBO reduces bowel symptoms.
Methods: Of 815 subjects undergoing lactulose hydrogen breath testing for assessment of SIBO, 123 patients had fibromyalgia. Those with SIBO were treated with antibiotics. At the initial and follow-up visits, subjects were asked to rate their symptoms. Symptom scores before and after treatment were compared.
Results: Of the 123 subjects with fibromyalgia, 96 (78%) were found to have SIBO. Returning subjects reported a 57+/- 29% overall improvement in symptoms with significant improvement in bloating, gas, abdominal pain, diarrhea, constipation, joint pains, and fatigue [P<0.05]. Conclusions: 1) Small intestinal bacterial overgrowth is associated with fibromyalgia. 2) Eradication of SIBO improves intestinal symptoms in fibromyalgia.
Details of the Study
Materials & Methods:
Consecutive patients referred to the Cedars-Sinai Medical Center Gastrointestinal Motility Program for a LHBT to diagnose SIBO were given a questionnaire and entered into a database. The questionnaire involved rating intestinal and extraintestinal symptoms such as bloating, gas, diarrhea, constipation, abdominal pain, joint pains, and fatigue on a scale ranging from 0-5, with 0 representing no symptoms. During the LHBT and before the results were available, affected subjects completed the questionnaire both before and after antibiotic treatment. From this database, subjects with fibromyalgia were identified on the basis of a bowel disease were excluded, as these subjects have an increased risk of developing SIBO. In addition, the prevalence of IBS within the group of fibromyalgia patients was determined by identifying subjects meeting Rome 1 Criteria (5).
All subjects diagnosed with SIBO by the LHBT were given a 10-day course of antibiotics by their referring physician [neomycin or ciprofloxacin each at 500mg po bid or flagyl 500mg pd tid] to eradicate their bacterial overgrowth. Those referred back for a follow-up LHBT approximately 10 days after completion of the antibiotics, were given a second questionnaire. Individual symptom ratings from the questionnaire were compared before and after treatment.
The database included 815 subjects. One hundred fifty-two subjects (19%) listed the diagnosis of fibromyalgia as part of their medical history. Twenty-nine of the 152 subjects also had inflammatory bowel disease (IBS) and were excluded, leaving 123 subjects for analysis. Of these 123 subjects, 63 (51%) were referred by a rheumatologist. Of the 63 subjects who were referred by a rheumatologist, 52 (83%) tested positive for SIBO. Twenty-three out of the 123 (19%) subjects had a coexisting connective tissue disease. One hundred seven of the 123 subjects (87%) met Rome 1 Criteria for IBS. Out of the 123 patients with fibromyalgia (87%), 96 tested positive for SIBO (78%) as diagnosed by the LHBT.
Twenty-five patients returned for a follow-up LHBT. Of these subjects, 11 achieved complete eradication and 14 achieved incomplete eradication of their SIBO. The antibiotics used in the treatment of SIBO in the 25 subjects were neomycin [N=18], augmentin [N=1], ciprofloxacin [N=1], flagyl [N=1], one subject was treated with both neomycin and ciprofloxacin, one was treated with neomycin, biaxin, and amoxicillin, and two subjects did not remember which antibiotics they took. Twenty-two of the 25 fibromyalgia subjects returning for their follow-up LHBT reported a 57 +/- 29% global improvement in symptoms. The three remaining subjects did not provide a percent global improvement.
The effectiveness of antibiotic treatment was assessed for symptoms and was suggested to be more pronounced when there was complete eradication compared to incomplete eradication. The percent decrease of abdominal pain was 68.8 +/- 28.8 in the complete eradication group, and 1.5 +/- 51.0 in the incomplete eradication group [P<0.05 after Bonferroni correction].
On the follow-up questionnaire, patients were then asked to list the symptom(s) most improved. Seventeen patients noted their abdominal complaints improved the most, 7 patients listed pain, 3 fatigue, and 1 reported sleeplessness was most improved.
From this data, there appears to be an improvement in bowel symptoms after treatment of SIBO in subjects with fibromyalgia. Bloating, gas, diarrhea, constipation, and abdominal pain, are all improved. More improvement is seen when eradication is complete. This data suggests that the bowel symptoms in fibromyalgia may be caused by SIBO. The causal role of a bacterial agent in fibromyalgia has been suggested previously. Links have been proposed between fibromyalgia and Chlamydia species (6) as well as Borrelia burgdorferi (7-9). None of these pathogens has clearly proven to be the causative agent for fibromyalgia. From studies in animal models, SIBO does result in bacterial translocation to mesenteric lymph nodes (10-13) and can produce systemic effects. These are believed to be mediated by endotoxin from Gram-negative bacteria (14-16). Such endotoxin related effects could explain the soft tissue hyperalgesia seen in fibromyalgia, since injection of endotoxin in lab animals can result in hyperalgesia (17-24).
In summary, this preliminary study suggests that the intestinal symptoms in fibromyalgia may be related to SIBO. Treatment of SIBO in these subjects results in an overall improvement in intestinal symptoms. Further studies using objective measures such as tender point examination or a scoring system such as the Fibromyalgia Impact Questionnaire (25) to assess the impact of eradication of SIBO on symptoms of fibromyalgia, are needed. In addition, a double blind study would be of great importance to substantiate the data.
1. Wolfe, F, Smythe, HA, Yunus, MB, Bennett, RM, Bombardier, C, Goldenberg, DL, Tugwell, P, Campbell, SM, Abeles, M, Clark, P, Fam, AG, Farber, SJ, Fiechtne, JJ, Franklin, CM, Gatter, RA, Hamaty, D, Lessard, J, Lichtbroun, AS, Masi, AT, McCain, GA, Reynolds, WJ, Romano, TJ, Russell, IJ, Sheon, RP: The American College of Rheumatology, 1990 criteria for the classification of fibromyalgia. Arthritis Rheum 33: 160-72, 1990.
2. 2. Triadafilopoulos, G, Simms, RW, Goldenberg, DI: Bowel dysfunction in fibromyalgia syndrome. Dig Dis Sci 36:59-64, 1991.
3. Hudson JI, Goldenberg DL, Pope HG, Jr., Keck PE, Jr., Schlesinger, L: Co-morbidity of fibromyalgia with medical and psychiatric disorders. AM J Med 92:363-7, 1992.
4. Veale D: Kavanagh, G, Fielding, JF, Fitzgerald O: Primary fibromyalgia and the irritable bowel syndrome: Different expressions of a common pathogenetic process. BR J Rheumatol 30:220-2, 1991.
5. Drossman DA, Richter JE, Talley, N, eds.: Functional gastrointestinal disorders: Diagnosis, pathophysiology and treatment: A multinational consensus. Little, Brown, Boston, 1994.
6. Machtey I: Chlamydia pneumoniae antibodies in myalgia of unknown cause [including fibromyalgia]. Br J. Rheumatol 36:1134, 1997.
7. Steere, AC: Musculoskeletal manifestations of Lyme disease. Am J Med 98:44S-48S, 1995.
8. Schned, ES, Williams, DN: Special concerns in Lyme disease. Seropositivity with vague symptoms and development of fibrositis. Postgrad Med 91:65-68, 70, 1992.
9. Sigal, LH: Summary of the first 100 patients at a Lyme disease referral center. AM J Med 88:577-581, 1990.
10. Berg, RD, Wommack, E, Deitch, EA: Immunosuppression and intestinal bacterial overgrowth synergistically promote bacterial translocation. Arch Surg 123:1359-64, 1988.
11. Wells, CL, Barton, RG, Jechorek, RP, Cerra, FB: Effect of three liquid diets on cecal bacterial flora and bacterial translocation in mice. Nutrition 7:358-63, 1991.
12. Guarner, C, Runyon, BA, Young, S, Heck, M, Sheikh, MY: Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rates with ascites. J Hepatol 26:1372-8, 1997.
13. Nieuwenhuijs, VB, Verheem, A, van Duijvenbode-Beumer, H, Visser, MR, Verhoef, J, Gooszen, HG, Akkermans, LM: The role of interdigestive small bowel motility in the regulation of gut microflora, bacterial overgrowth, and bacterial translocation in rats. Ann Surg 188-93, 1998.
14. Lichtman, SN, Sartor, RB, Keku, J, Schwab, JH, Sartor, RB: Bilary tract diseases in rats with experimental small bowel bacterial overgrowth. Hepatology 13:766-82, 1990.
15. Lichtman, SN, Sartor RB, Keku, J, Schwab, JH: Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology, 98:414-23, 1990.
16. Riordan, SM, McIvor, CJ, Williams, R: Liver damage in human small intestinal bacterial overgrowth. Am J Gastroenterology, 93:234-7, 1998.
17. Maier, SF, Wiertelak, EP, Martin, D, Watkins, LR: Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin. Brain Res 623:321-4, 1993.
18. Watkins, LR, Wiertelak, EP, Goehler, L, Mooney-Heiberger, K, Martinez, J, Furness, L, Smith, KD, Maier, SF: Neurocircuitry of illness-induced hyperalgesia. Brain Res 639:283-299, 1994.
19. Watkins, LR, Wiertelag, EP, Furness, LE, Maier, SF: Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids. Brain Res 664:17-24, 1994.
20. Wiertelak, EP, Smith, KP, Furness, L, Mooney-Heiberger, K, Mayr, T, Maier, SF, Watkins, LR: Acute and conditioned hyperalgesic responses to illness. Pain 56:227-34, 1994.
21. Kanaan, SA, Saade, NE, Haddad, JJ, Abdelnoor, AM, Atweh, SF, Jabbur, SJ, Safieh-Garabedian, B: Endotoxin-induced local inflammation and hyperalgesia in rats and mice: A new model for inflammatory pain. Pain 66:373-9, 1996.
22. Cahill, CM, Dray, A, Coderre, TJ: Priming enhances endotoxin-induced thermal hyperalgesia and mechanical allodynia in rats. Brain Res 808:13-22, 1998
23. Walker, K, Dray, A, Perkins, M: Development of hyperthermia and hyperalgesia following intracerebroventricular administration of endotoxin in the rat: Effect of kinan B1 and B2 receptor antagonists. Immunopharmacology 33:264-9, 1996.
24. Walker, K, Dray, A, Perkins, M: Hyperalgesia in rats following the intracerebroventricular administration of endotoxin: Effect of bradykinin B1 and B2 receptor antagonists. Pain 65:211-9, 1996.
25. Burckhardt, CS, Clark, SR, Bennett, RM: The fibromyalgia impact questionnaire: Development and validation. J Rheumatol 18:728-33, 1991.