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Possible Causes

Gut Influences

One’s cognitive functions, emotions, state of mind, and overall health (including the presence of chronic pain) are influenced by the bugs living in the gut. Digestive tract microbes (called your microbiota) form a diversified ecosystem and they can impact how the CNS functions.

The gastrointestinal tract is surrounded by a nervous system that forms a two-way communication highway with the CNS. In addition, more than 70 percent of the body’s immune cells reside alongside the digestive system. When these cells are activated by changes in the microbiota, they pump cytokine chemicals into the bloodstream. Cytokines are mind-altering and pain-enhancing substances capable of activating the CNS, especially the microglia.

Research shows that fibromyalgia patients possess undesirable alterations in their microbiota that are contributing to the condition and possibly causing it.1 There are decreases in several bacteria that help maintain the integrity of the intestinal lining, while those that degrade the lining are increased. This microbiota imbalance leads to two serious problems: (1) a leaky gut and (2) an increase in bile acid production.

A leaky gut prompts the immune cells lining the intestines to release cytokines into the bloodstream, which can activate the microglia in the CNS. While studies show that blood cytokines are increased in fibromyalgia, the source of these cytokines is unclear. The gut seems to be a likely culprit. With regards to microglia activation, this has been documented in several brain imaging studies in fibromyalgia.

Bile acids may seem off topic for a discussion of widespread pain, but recent research provides compelling evidence that these acids are linked to the symptoms of fibromyalgia.2 First of all, the liver releases bile acids into the intestines to aid with the digestion of fats. Then it is up to the gut microbiota to metabolize the bile acids and here is where the imbalance in gut microbes is linked to the key symptoms of fibromyalgia.

Certain microbes that transform bile acids into pain-sensitizing substances are increased in fibromyalgia, while those that change bile acids into analgesic agents are one-fifth of normal. But how do the bile acids signal the CNS to cause pain and the other symptoms of fibromyalgia? They are suspected to sensitize the dorsal root ganglia (the structures that house the nucleus of each neuron) and this can boost the intensity of the signal entering the spinal cord.

Although the mechanisms by which the various bile acids exert their effects on the CNS are based on animal models, the finding that their concentrations correlated with the level of pain, fatigue, and overall symptom severity scores cannot be dismissed. 

Elevated blood glutamate levels are another finding that links alterations in the microbiota in fibromyalgia patients.3 Microbes that consume glutamate to make GABA are depleted in people with fibromyalgia (remember, glutamate enhances pain while GABA relieves it). And given the leaky gut in many fibromyalgia patients, the excess glutamate can enter the blood and can irritate the nerve endings in the tissues. However, this pain-promoting chemical cannot cross the blood-brain barrier, but it can signal the CNS through the neurological connections.

Another transmitter produced by the GI system is serotonin. In fact, the body’s largest supply of serotonin comes from the gut.4 Your digestive system converts tryptophan into serotonin and changes in the microbiota can alter serotonin production, which in turn can make it harder for your CNS to control pain, mood, and anxiety.

One could talk about the other possible roles that the microbiota exerts on providing essential vitamins, defense against pathogens, and modulating brain function, including mood, anxiety, and cognition. Appreciation of the eco system in the gut is relatively new, but it’s definitely a strong contender for contributing to the symptoms of fibromyalgia.

If gut microbiome imbalances are the source of your symptoms, what can be done to counter them? Studies show that the diet of people with fibromyalgia is the same as that of healthy, pain-free control subjects.5 So, abnormal eating habits probably are not causing the gut dysfunction. Yet, there are a few foods thought to reduce bile acids: avocados, blueberries, and walnuts.

The ideal diet for a healthy gut consists of fresh fruit and vegetables, low fat meat, fibers, and devoid in refined sugar, vegetable oils, and refined cereals. Whether such a diet will help is not known, but it can’t hurt. Also, one should try to reduce dietary glutamate (such as MSG and other flavor enhancers in processed foods) because the bacteria needed to convert this pain transmitter into GABA is deficient in people with fibromyalgia. See the Diet & Nutrition section for guidance on this special diet. 

Bacteria in the Bifidobacterium family are reduced, but it’s unknown if supplementing one’s diet with this probiotic will help due to the complexity of the microbiome.

Now, if you are still uncertain about the role that your gut plays in producing your fibromyalgia symptoms, a recent multi-center study provides compelling evidence. Transfer of gut microbiota from fibromyalgia patients to mice caused a rapid onset of pain in the mice. It even produced many of the CNS changes that are found in people with fibromyalgia, such as microglia activation.6 In addition, transfer of microbiota from healthy subjects into fibromyalgia patients significantly reduced symptoms.

  1. Minerbi A, Fitzcharles MA. Clin Exp Rheum 38(suppl 123):S99-S104, 2020.
  2. Minerbi A, et al. PAIN 164:e66-e76, 2023.
  3. Clos-Garcia M, et al. EBioMedicine 46:499-511, 2019.
  4. Roth W, at al. Int J Mol Sci 22:2973, 2021.
  5. Minerbi A, at al. Int J Environ Res Public Health 19:3254, 2022.
  6. Cai W, Shir Y, Minerbi A, Khoutorsky A, et al. BioRxiv October 28, 2023.