with fibromyalgia are more likely to show dysbiosis, a decrease in microbiota diversity. there is a bidirectional interplay between the gut and the nervous system. therefore, the gut can affect the nervous system, but the nervous system can also affect the gut. neurological effects mediated via the autonomic nervous system as well as the hypothalamic pituitary adrenal axis are directed to intestinal functional effector cells, which in turn are under the influence of the gut microbiota. gut-brain axis the gut-brain axis, which connects the gut microbiome to the brain via the enteric nervous system, is another area of research. fibromyalgia patients have less varied gut flora and altered serum metabolome levels of glutamate and serine, implying abnormalities in neurotransmitter metabolism. diagnosis the location of the nine paired tender points that comprise the 1990 american college of rheumatology criteria for fibromyalgia there is no single pathological feature, laboratory finding, or biomarker that can diagnose fibromyalgia and there is debate over what should be considered diagnostic criteria and whether an objective diagnosis is possible. in most cases, people with fibromyalgia symptoms may have laboratory test results that appear normal and many of their symptoms may mimic those of other rheumatic conditions such as arthritis or osteoporosis. the specific diagnostic criteria for fibromyalgia have evolved over time. american college of rheumatology 1990 the first widely accepted set of classification criteria for research purposes was elaborated in 1990 by the multicenter criteria committee of the american college of rheumatology. these criteria, which are known informally as "the acr 1990", defined fibromyalgia according to the presence of the following criteria: a history of widespread pain lasting more than three months – affecting all four quadrants of the body, i.e., both sides, and above and below the waist. tender points – there are 18 designated possible tender points (although a person with the disorder may feel pain in other areas as well). the acr criteria for the classification of patients were originally established as inclusion criteria for research purposes and were not intended for clinical diagnosis but have later become the de facto diagnostic criteria in the clinical setting. a controversial study was done by a legal team looking to prove their client's disability based primarily on tender points and their widespread presence in non-litigious communities prompted the lead author of the acr criteria to question now the useful validity of tender points in diagnosis. use of control points has been used to cast doubt on whether a person has fibromyalgia, and to claim the person is malingering. american college of rheumatology 2010 provisional criteria widespread pain index (wpi) areas in 2010, the american college of rheumatology approved provisional revised diagnostic criteria for fibromyalgia that eliminated the 1990 criteria's reliance on tender point testing. the revised criteria used a widespread pain index (wpi) and symptom severity scale (sss) in place of tender point testing under the 1990 criteria. the wpi counts up to 19 general body areas in which the person has experienced pain in the preceding week. the sss rates the severity of the person's fatigue, unrefreshed waking, cognitive symptoms, and general somatic symptoms, each on a scale from 0 to 3, for a composite score ranging from 0 to 12. the revised criteria for diagnosis were: wpi ≥ 7 and sss ≥ 5 or wpi 3–6 and sss ≥ 9, symptoms have been present at a similar level for at least three months, and no other diagnosable disorder otherwise explains the pain.: 607 american college of rheumatology 2016 revisions in 2016, the provisional criteria of the american college of rheumatology from 2010 were revised. the new diagnosis required all of the following criteria: "generalized pain, defined as pain in at least 4 of 5 regions, is present." "symptoms have been present at a similar level for at least 3 months." "widespread pain index (wpi) ≥ 7 and symptom severity scale (sss) score ≥ 5 or wpi of 4–6 and sss score ≥ 9." "a diagnosis of fibromyalgia is valid irrespective of other diagnoses. a diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses." american pain society 2019 in 2019, the american pain society in collaboration with the u.s. food and drug administration developed a new diagnostic system using two dimensions. the first dimension included core diagnostic criteria and the second included common features. in accordance to the 2016 diagnosis guidelines, the presence of another medical condition or pain disorder does not rule out the diagnosis of fibromyalgia. nonetheless, other conditions should be ruled out as the main explaining reason for the patient's symptoms. the core diagnostic criteria are: multisite pain defined as six or more pain sites from a total of nine possible sites, for at least three months moderate to severe sleep problems or fatigue, for at least three months common features found in fibromyalgia patients can assist the diagnosis process. these are tenderness (sensitivity to light pressure), dyscognition (difficulty to think), musculoskeletal stiffness, and environmental sensitivity or hypervigilance. self-report questionnaires some research has suggested using a multidimensional approach taking into consideration somatic symptoms, psychological factors, psychosocial stressors and subjective belief regarding fibromyalgia. these symptoms can be assessed by several self-report questionnaires. widespread pain index (wpi) the widespread pain index (wpi) measures the number of painful body regions. symptom severity scale (sss) the symptom severity scale (sss) assesses the severity of the fibromyalgia symptoms. fibromyalgia impact questionnaire (fiq) the fibromyalgia impact questionnaire (fiq) and the revised fibromyalgia impact questionnaire (fiqr) assess three domains: function, overall impact and symptoms. it is considered a useful measure of disease impact. other questionnaires other measures include the hospital anxiety and depression scale, multiple ability self-report questionnaire, multidimensional fatigue inventory, and medical outcomes study sleep scale. differential diagnosis as of 2009, as many as two out of every three people who are told that they have fibromyalgia by a rheumatologist may have some other medical condition instead. fibromyalgia could be misdiagnosed in cases of early undiagnosed rheumatic diseases such as preclinical rheumatoid arthritis, early stages of inflammatory spondyloarthritis, polymyalgia rheumatica, myofascial pain syndromes and hypermobility syndrome. neurological diseases with an important pain component include multiple sclerosis, parkinson's disease and peripheral neuropathy. other medical illnesses that should be ruled out are endocrine disease or metabolic disorder (hypothyroidism, hyperparathyroidism, acromegaly, vitamin d deficiency), gastro-intestinal disease (celiac and non-celiac gluten sensitivity), infectious diseases (lyme disease, hepatitis c and immunodeficiency disease) and the early stages of a malignancy such as multiple myeloma, metastatic cancer and leukemia/lymphoma. other systemic, inflammatory, endocrine, rheumatic, infectious, and neurologic disorders may cause fibromyalgia-like symptoms, such as systemic lupus erythematosus, sjögren syndrome, ankylosing spondylitis, ehlers-danlos syndromes, psoriatic-related polyenthesitis, a nerve compression syndrome (such as carpal tunnel syndrome), and myasthenia gravis. in addition, several medications can also evoke pain (statins, aromatose inhibitors, biophosphonates, and opioids). the differential diagnosis is made during the evaluation on the basis of the person's medical history, physical examination, and laboratory investigations. the patient's history can provide some hints to a fibromyalgia diagnosis. a family history of early chronic pain, a childhood history of pain, an emergence of broad pain following physical and/or psychosocial stress, a general hypersensitivity to touch, smell, noise, taste, hypervigilance, and various somatic symptoms (gastrointestinal, urology, gynecology, neurology), are all examples of these signals extensive laboratory tests are usually unnecessary in the differential diagnosis of fibromyalgia. common tests that are conducted include complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, c-reactive protein, and thyroid function test. management as with many other medically unexplained syndromes, there is no universally accepted treatment or cure for fibromyalgia, and treatment typically consists of symptom management and improving patient quality of life. a personalized, multidisciplinary approach to treatment that includes both non-pharmacologic and pharmacologic therapy and begins with effective patient education is most beneficial. developments in the understanding of the pathophysiology of the disorder have led to improvements in treatment, which include prescription medication, behavioral intervention, and exercise. a number of associations have published guidelines for the diagnosis and management of fibromyalgia. the european league against rheumatism (eular; 2017) recommends a multidisciplinary approach, allowing a quick diagnosis and patient education. the recommended initial management should be non-pharmacological, later pharmacological treatment can be added. the european league against rheumatism gave the strongest recommendation for aerobic and strengthening exercise. weak recommendations were given to a number of treatments, based on their outcomes. qigong, yoga, and tai chi were weakly recommended for improving sleep and quality of life. mindfulness was weakly recommended for improving pain and quality of life. acupuncture and hydrotherapy were weakly recommended for improving pain. a weak recommendation was also given to psychotherapy. it was more suitable for patients with mood disorders or unhelpful coping strategies. chiropractic was strongly recommended against, due to safety concerns. some medications were weakly recommended for severe pain (duloxetine, pregabalin, tramadol) or sleep disturbance (amitriptyline, cyclobenzaprine, pregabalin). others were not recommended due to a lack of efficacy (nonsteroidal anti-inflammatory drugs, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors). growth hormone, sodium oxybate, opioids and steroids were strongly recommended against due to lack of efficacy and side effects. the guidelines published by the association of the scientific medical societies in germany inform patients that self-management strategies are an important component in managing the disease. the canadian pain society also published guidelines for the diagnosis and management of fibromyalgia. exercise exercise is the only fibromyalgia treatment which has been given a strong recommendation by the european alliance of associations for rheumatology (eular). there is strong evidence indicating that exercise improves fitness, sleep and quality of life and may reduce pain and fatigue for people with fibromyalgia. exercise has an added benefit in that it does not cause any serious adverse effects. exercise may diminish fibromyalgia symptoms through a number of hypothesized biological mechanisms. exercise may improve pain modulation through serotoninergic pathways. it may reduce pain by altering the hypothalamic-pituitary-adrenal axis and reducing cortisol levels. it also has anti-inflammatory effects that may improve fibromyalgia symptoms. aerobic exercise can improve muscle metabolism and pain through mitochondrial pathways. when comparing different exercise programs, aerobic exercise is capable of modulating the autonomic nervous function of fibromyalgia patients, whereas resistance exercise does not show such effects. a 2022 meta-analysis found that aerobic training showed a high effect size while strength interventions showed moderate effects. meditative exercise seems preferable for improving sleep, with no differences between resistance, flexibility and aquatic exercise in their favorable effects on fatigue. despite its benefits, exercise is a challenge for patients with fibromyalgia, due to the chronic fatigue and pain they experience. they perceive it as more effortful than healthy adults. exercise may intimidate them, in fear that they will be asked to do more than they are capable of. they may also feel that those who recommend or deliver exercise interventions do not fully understand the possible negative impact of exercise on fatigue and pain. this is especially true for non-personalized exercise programs. adherence is higher when the exercise program is recommended by doctors or supervised by nurses. depression and higher pain intensity serve as barriers to physical activity. a recommended approach to a graded exercise program begins with small, frequent exercise periods and builds up from there. in order to reduce pain, it is recommended to use an exercise program of 13 to 24 weeks, with each session lasting 30 to 60 minutes. aerobic aerobic exercise for fibromyalgia patients is the most investigated type of exercise. it includes activities such as walking, jogging, spinning, cycling, dancing and exercising in water, with walking being named as one of the best methods. a 2017 cochrane summary concluded that aerobic exercise probably improves quality of life, slightly decreases pain and improves physical function and makes no difference in fatigue and stiffness. a 2019 meta-analysis showed that exercising aerobically can reduce autonomic dysfunction and increase heart rate variability. this happens when patients exercise at least twice a week, for 45–60 minutes at about 60%-80% of the maximum heart rate. aerobic exercise also decreases anxiety and depression and improves the quality of life. flexibility combinations of different exercises such as flexibility and aerobic training may improve stiffness. however, the evidence is of low-quality. it is not clear if flexibility training alone compared to aerobic training is effective at reducing symptoms or has any adverse effects. resistance in resistance exercise, participants