Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved the treatment of RA, patients often inquire about dietary interventions to improve RA symptoms, as they perceive pain and/or swelling after the consumption or avoidance of certain foods. There is evidence that some foods have pro- or anti-inflammatory effects mediated by diet-related metabolites. In addition, recent literature has shown a link between diet-related metabolites and microbiome changes, since the gut microbiome is involved in the metabolism of some dietary ingredients. But diet and the gut microbiome are not the only factors linked to circulating pro- and anti-inflammatory metabolites. Other factors including smoking, associated comorbidities, and therapeutic drugs might also modify the circulating metabolomic profile and play a role in RA pathogenesis. This article summarizes what is known about circulating pro- and anti-inflammatory metabolites in RA. It also emphasizes factors that might be involved in their circulating concentrations and diet-related metabolites with a beneficial effect in RA.

Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson’s disease, suggesting a potential role of these lipids as biomarkers. This project’s objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson’s patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson’s patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography–mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson’s groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson’s and GBA1-mutation-carrier Parkinson’s patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson’s. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson’s groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson’s patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients.

Inflammatory responses are associated with changes in tissue metabolism. Prior studies find altered metabolomic profiles in both the synovial fluid (SF) and serum of osteoarthritis subjects. Our study determined the metabolomic profile of synovial tissue (ST) and SF of individuals with osteoarthritis (OA) and its association with synovial inflammation. 37 OA ST samples were collected during joint replacement, 21 also had SF. ST samples were fixed in formalin for histological analysis, cultured (explants) for cytokine analysis by enzyme-linked immunosorbent assay, or snap-frozen for metabolomic analysis. ST samples were categorized by Krenn synovitis score and picrosirius red. CD68 and vimentin expression was assessed by immunohistochemistry and semi-quantified using Image J. Proton-nuclear magnetic resonance (¹H NMR) was used to acquire a spectrum from ST and SF samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification. Metaboanalyst 5.0, SPSS v26, and R (v4.1.2) were used for statistical analysis. 42 and 29 metabolites were detected in the ST and SF respectively by ¹H NMR. Only 3 metabolites, lactate, dimethylamine, and creatine positively correlated between SF and ST. ST concentrations of several metabolites (lactate, alanine, fumarate, glutamine, glycine, leucine, lysine, methionine, trimethylamine N-oxide, tryptophan and valine) were associated with synovitis score, mostly to the lining score. IL-6, acetoacetate, and tyrosine in SF predicted high Krenn synovitis scores in ST. Metabolomic profiling of ST identified metabolic changes associated with inflammation. Further studies are needed to determine whether metabolomic profiling of synovial tissue can identify new therapeutic targets in osteoarthritis.

Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in the TNFRSF11B osteoprotegerin (OPG) gene has been related to postmenopausal OP although, to date, no information has been described concerning whether this polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We evaluated, in a case-control study performed in Mexican-Mestizo women with RA, whether SNP rs2073618 in the TNFRSF11B gene is associated with a decrease in BMD. RA patients were classified as follows: (1) low BMD and (2) normal BMD. All patients were genotyped for the rs2073618 polymorphism by PCR-RFLP. The frequency of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal BMD (62 and 54 years, resp.; p<0.001). Worse functioning and lower BMI were observed in RA with low BMD (p=0.003 and p=0.002, resp.). We found similar genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype 71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; p=0.6). We concluded that in Mexican-Mestizo female patients with RA, the rs2073618 polymorphism of the TNRFS11B gene is not associated with low BMD.