GC-MS-based fecal metabolomics reveals gender-attributed fecal signatures in ankylosing spondylitis.
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ABSTRACT:
SUBMITTER: He Z
PROVIDER: S-EPMC6405849 | biostudies-other | 2019 Mar
REPOSITORIES: biostudies-other
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Project description:Ankylosing spondylitis (AS) is a type of spondyloarthropathies, the diagnosis of which is often delayed. The lack of early diagnosis tools often delays the institution of appropriate therapy. This study aimed to investigate the systemic metabolic shifts associated with AS and TNF inhibitors treatment. Additionally, we aimed to define reliable serum biomarkers for the diagnosis. We employed an untargeted technique, ultra-performance liquid chromatography-mass spectroscopy (LC-MS), to analyze the serum metabolome of 32 AS individuals before and after 24-week TNF inhibitors treatment, as well as 40 health controls (HCs). Multivariate and univariate statistical analyses were used to profile the differential metabolites associated with AS and TNF inhibitors. A diagnostic panel was established with the least absolute shrinkage and selection operator (LASSO). The pathway analysis was also conducted. A total of 55 significantly differential metabolites were detected. We generated a diagnostic panel comprising five metabolites (L-glutamate, arachidonic acid, L-phenylalanine, PC (18:1(9Z)/18:1(9Z)), 1-palmitoylglycerol), capable of distinguishing HCs from AS with a high AUC of 0.998, (95%CI: 0.992-1.000). TNF inhibitors treatment could restore the equilibrium of 21 metabolites. The most involved pathways in AS were amino acid biosynthesis, glycolysis, glutaminolysis, fatty acids biosynthesis and choline metabolism. This study characterized the serum metabolomics signatures of AS and TNF inhibitor therapy. We developed a five-metabolites-based panel serving as a diagnostic tool to separate patients from HCs. This serum metabolomics study yielded new knowledge about the AS pathogenesis and the systemic effects of TNF inhibitors.
| S-EPMC7933516 | biostudies-literature
Project description:ObjectiveThe study objective was to explore differences in ankylosing spondylitis (AS) diagnosis experiences between men and women by examining the coding of health events over the 2 years preceding AS diagnosis.MethodsClaims data (January 2006-April 2019) from the MarketScan databases were examined. Patients who had received two or more AS diagnoses at least 30 days apart and had at least 2 years of insurance enrollment before their first AS diagnosis were analyzed. Men were matched 1:1 to women by age, diagnosis date, insurance type, and enrollment duration. Health events (diagnosis and provider codes) were examined over 2 years before AS diagnosis and stratified by gender. Data were analyzed using univariate χ2 tests.ResultsAmong 7744 patients, 274 of 1906 AS-related codes showed statistically significant differences between men and women. Women received more diagnosis codes than men across diagnoses and providers; the largest difference in diagnosis codes among women versus men was in peripheral symptom coding (57.7% vs. 43.9%, respectively). More women than men received diagnosis codes for depression (21.2% vs. 9.8%) and other musculoskeletal symptoms (52.8% vs. 40.0%); only gout was more common in men (6.5%) than in women (2.2%). Among men, backache codes gradually increased 12 months before AS diagnosis, whereas axial and sacroiliitis coding increased sharply immediately before diagnosis. The greatest difference in physician types visited was for rheumatologists: 64.2% of women had visits compared with 45.1% of men.ConclusionFurther investigation into the dissimilarities in diagnostic experiences between men and women is needed to determine whether differences are due to disease phenotype or potential cognitive bias influencing diagnostic decision-making.
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Project description:The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS families and showed that novel genetic markers in the 5' flanking region of ANKH (the human homolog of the murine ank gene) are modestly associated with AS. The objective of the present study was to conduct a more extensive evaluation of ANKH variants that are significantly associated with AS and to determine whether the association is gender specific. We genotyped 201 multiplex AS families with nine ANKH intragenetic and two flanking microsatellite markers, and performed family-based association analyses. We showed that ANKH variants located in two different regions of the ANKH gene were associated with AS. Results of haplotype analyses indicated that, after Bonferroni correction, the haplotype combination of rs26307 [C] and rs27356 [C] is significantly associated with AS in men (recessive/dominant model; P = 0.004), and the haplotype combination of rs28006 [C] and rs25957 [C] is significantly associated with AS in women (recessive/dominant model; P = 0.004). A test of interaction identified rs26307 (i.e. the region that was associated in men with AS) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance in the test of interaction among the subset of families with affected individuals of both genders. These findings support the concept that ANKH plays a role in genetic susceptibility to AS and reveals a gender-genotype specificity in this interaction.
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Project description:Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut-joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.
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Project description:The development of improved mass spectrometers and supporting computational tools is expected to enable the rapid annotation of whole metabolomes. Essential for the progress is the identification of strengths and weaknesses of novel instrumentation in direct comparison to previous instruments. Orbitrap liquid chromatography (LC)-mass spectrometry (MS) technology is now widely in use, while Orbitrap gas chromatography (GC)-MS introduced in 2015 has remained fairly unexplored in its potential for metabolomics research. This study aims to evaluate the additional knowledge gained in a metabolomics experiment when using the high-resolution Orbitrap GC-MS in comparison to a commonly used unit-mass resolution single-quadrupole GC-MS. Samples from an osmotic stress treatment of a non-model organism, the microalga Skeletonema costatum, were investigated using comparative metabolomics with low- and high-resolution methods. Resulting datasets were compared on a statistical level and on the level of individual compound annotation. Both MS approaches resulted in successful classification of stressed vs. non-stressed microalgae but did so using different sets of significantly dysregulated metabolites. High-resolution data only slightly improved conventional library matching but enabled the correct annotation of an unknown. While computational support that utilizes high-resolution GC-MS data is still underdeveloped, clear benefits in terms of sensitivity, metabolic coverage, and support in structure elucidation of the Orbitrap GC-MS technology for metabolomics studies are shown here.
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