Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome

Table 2 Summary of studies reporting significant differences in body fluids composition of fibromyalgia patients (P ≤ 0.05)

Ref.	Population studied/study design	Diagnosis criteria	Sample	Technique	Metabolite with increased levels					Metabolite with decreased levels
Menzies et al[23], 2020	20 FMS (20 F, 0 M). 20 HC (20 F, 0 M). Mean age in both groups 41.9 yr. Age range and medium age NA	ACR 1990 criteria	Plasma	LC-MS	Amino acid metabolism	Taurine		P < 0.001		Energy metabolism		2-hydroxyglutarate	P < 0.001
						Methionine sulfoxide
						Anthranilate
					Lipid metabolism	Lysophosphocholines (16:0)
						Lysophosphocholines (18:0)
						Lysophosphocholines (20:4)		P = 0.001				Alpha-ketoglutaric acid	NA
						Lysophosphocholines (22:6)
						Lysophosphocholines (18:1)		P = 0.003
						Lysophosphocholines (16:1)		P = 0.007
Caboni et al[24], 2014	22 FMS (22 F, 0 M). Age range 27-72 yr. Mean age 52 yr. 21 HC (21 F, 0 M). Age range 27-67 yr. Mean age 50 yr. Median age NA	ACR criteria	Plasma	LC-Q-TOF/MS	1-hexadecanoyl-sn-glycero-3-phosphocholine [PC (16:0)]			NA		NA
					1-tetradecanoyl-sn-glycero-3-phosphocholine [PC (14:0)]
Clos-Garcia et al[25], 2019	105 FMS (73 F, 32 M). 54 HC (26 F, 28 M). Age range and mean and medium age NA	ACR 2010 criteria	Serum	UPLC-MS	Ornithine			NA		Platelet activating factor (PAF-16)			NA
					L-arginine
					Nε-Methyl-L-lysine
					L-glutamate
					Asymmetric dimethylarginine (ADMA)
					l-threonine/DL-homoserin
					L-glutamine
Hackshaw et al[26], 2013	10 FMS (9 F, 1 M). Mean age 50 yr. 10 OA (7 F, 3 M). Mean age 65 yr. 10 RA (9 F, 1 M). Mean age 60 yr. Age range and median age NA	ARC criteria	Blood	UHPLC/MS/MS	Trans-urocanate			NA		NA			NA
					Asparagine
					Heme
					Cysteine–glutathione disulfide
					Glucose
					Pyruvate
					Nicotinamide adenine dinucleotide (NAD+)
Malatji et al[27], 2019	17 FMS (17 F, 0 M). 62 HC (62 F, 0 M), 11 CF, 10 CO, 41 CN (age range 18-22 yr). Median and mean age: NA	ACR 1990 criteria	Urine	GC-MS	3-D-Ribohexonic acid								P = 0.0000089
					Sorbose								P < 0.00001
					Threonic acid
					Erythropentonic acid
					2-Keto-1-gluconic acid
					2-hydroxyglutaric acid								P = 0.000013
					Arabinose								P = 0.000017
					2-D-3,5-DHPL								P = 0.000019
					2,3,4-Trihydroxybutyl-L								P = 0.000021
					Phosphoric acid								P = 0.00011
					Glutaric acid
					Oxalic acid
					Rhamnose
					Tagatose								P = 0.00024
					4-HBA								P = 0.00109
					Malic acid								P = 0.024
Malatji et al[28], 2017	18 FMS (18 F, 0 M). 41 HC (41 F, 0 M), 11 FR, 10 AM, 20 YHC (age range 18-22 yr). Median and mean age NA	ARC 1990 criteria	Urine	QE-MS	Gut microbiome		Succinic acid		P = 0.0001		NA
							Lactic acid		P = 0.0044
							Hippuric		P = 0.09
					Osmolytes		Taurine		P = 0.0007
							TMAO		P = 0.006

ACR: American College of Rheumatology; B: Both; CFS: chronic fatigue syndrome; F: Female; GC-MS: Gas chromatography-mass spectrometry; HC: Healthy control; LC-MS: Liquid chromatography-mass spectrometry; LC-Q-TOF/MS: Liquid chromatography quadrupole time-of-flight mass spectrometry; M: Male; NA: Not available; QE-MS: Q exactive mass spectrometer; TMAO: Trimethylamine N-oxide; UPLC-MS: Ultra-performance liquid chromatography-mass spectrometry.