Dataset Information

Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis.

ABSTRACT:

Background

Fatty acids have diverse immunomodulatory functions and the potential to be associated with inflammatory responses in sarcoidosis.

Methods

The serum levels of multiple long-chain fatty acids (LCFAs) were compared between 63 patients with sarcoidosis and 38 healthy controls. The associations of LCFAs with clinical outcomes of sarcoidosis were also evaluated.

Results

The patients with sarcoidosis had significantly lower levels of n-3 poly-unsaturated fatty acids (PUFAs) (p < 0.001) and n-6 PUFAs (p < 0.001) than the healthy controls. However, there were no significant differences in the levels of saturated fatty acids (SFAs) and mono-unsaturated fatty acids (MUFAs) between the two groups. On multivariate logistic analysis, lower levels of n-3 PUFAs, n-6 PUFAs, and n-3/n-6 ratio were predictive of sarcoidosis. Among the patients with sarcoidosis, those with multiple organ involvement had significantly lower levels of n-3 PUFAs and n-3/n-6 ratio than those with single organ involvement. There were no significant differences in the levels of n-6 PUFAs, SFAs, and MUFAs between the patients with multiple and single organ involvement. On multivariate logistic analysis, lower levels of SFAs and n-3/n-6 ratio were predictive of multiple organ involvement. The levels of LCFAs had no significant association with radiographic stage or spontaneous remission.

Conclusions

Assessment of LCFA profiles may be useful for the diagnosis of sarcoidosis and evaluation of the disease activity.

SUBMITTER: Suzuki T

PROVIDER: S-EPMC9335968 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis.

Suzuki Takahito T Karayama Masato M Inoue Yusuke Y Hozumi Hironao H Suzuki Yuzo Y Furuhashi Kazuki K Fujisawa Tomoyuki T Enomoto Noriyuki N Nakamura Yutaro Y Inui Naoki N Suda Takafumi T

BMC pulmonary medicine 20220728 1

<h4>Background</h4>Fatty acids have diverse immunomodulatory functions and the potential to be associated with inflammatory responses in sarcoidosis.<h4>Methods</h4>The serum levels of multiple long-chain fatty acids (LCFAs) were compared between 63 patients with sarcoidosis and 38 healthy controls. The associations of LCFAs with clinical outcomes of sarcoidosis were also evaluated.<h4>Results</h4>The patients with sarcoidosis had significantly lower levels of n-3 poly-unsaturated fatty acids (P ...[more]

PMID: 35902843

Similar Datasets

Project description:Multiple sclerosis (MS) is a chronic immune-mediated disease characterized by demyelination and neuroaxonal damage in the central nervous system. The etiology is complex and is still not fully understood. Accumulating evidence suggests that our gut microbiota and its metabolites influence the MS pathogenesis. Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are metabolites produced by gut microbiota through fermentation of indigestible carbohydrates. SCFAs and kynurenine metabolites have been shown to have important immunomodulatory properties, and propionate supplementation in MS patients has been associated with long-term clinical improvement. However, the underlying mechanisms of action and its importance in MS remain incompletely understood. We analyzed serum levels of SCFAs and performed targeted metabolomics in relation to biomarkers of inflammation, and clinical and MRI measures in newly diagnosed patients with relapsing-remitting MS before their first disease modifying therapy and healthy controls (HCs). We demonstrated that serum acetate levels were nominally reduced in MS patients compared with HCs. The ratios of acetate/butyrate and acetate/(propionate + butyrate) were significantly lower in MS patients in a multivariate analysis (orthogonal partial least squares discriminant analysis; OPLS-DA). The mentioned ratios and acetate levels correlated negatively with the pro-inflammatory biomarker IFNG, indicating an inverse relation between acetate and inflammation. In contrast, the proportion of butyrate was found higher in MS patients in the multivariate analysis, and both butyrate and valerate correlated positively with proinflammatory cytokines (IFNG and TNF), suggesting complex bidirectional regulatory properties of SCFAs. Branched SCFAs were inversely correlated with clinical disability, at a nominal significance level. Otherwise SCFAs did not correlate with clinical variables or MRI measures. There were signs of an alteration of the kynurenine pathway in MS, and butyrate was positively correlated with the immunomodulatory metabolite 3-hydroxyanthranilic acid. Other variables that influenced the separation between MS and HCs were NfL, ARG1 and IL1R1, D-ribose 5-phosphate, pantothenic acid and D-glucuronic acid. In conclusion, we provide novel results in this rapidly evolving field, emphasizing the complexity of the interactions between SCFAs and inflammation; therefore, further studies are required to clarify these issues before supplementation of SCFAs can be widely recommended.

Project description:Concerns about global warming, fossil-fuel depletion, food security, and human health have promoted metabolic engineers to develop tools/strategies to overproduce microbial functional oils directly from renewable resources. Medium-chain fatty acids (MCFAs, C8-C12) have been shown to be important sources due to their diverse biotechnological importance, providing benefits ranging from functional lipids to uses in bio-fuel production. However, oleaginous microbes do not carry native pathways for the production of MCFAs, and therefore, diverse approaches have been adapted to compensate for the requirements of industrial demand. Mucor circinelloides is a promising organism for lipid production (15-36% cell dry weight; CDW) and the investigation of mechanisms of lipid accumulation; however, it mostly produces long-chain fatty acids (LCFAs). To address this challenge, we genetically modified strain M. circinelloides MU758, first by integrating heterologous acyl-ACP thioesterase (TE) into fatty acid synthase (FAS) complex and subsequently by modifying the β-oxidation pathway by disrupting the acyl-CoA oxidase (ACOX) and/or acyl-CoA thioesterase (ACOT) genes with a preference for medium-chain acyl-CoAs, to elevate the yield of MCFAs. The resultant mutant strains (M-1, M-2, and M-3, respectively) showed a significant increase in lipid production in comparison to the wild-type strain (WT). MCFAs in M-1 (47.45%) was sharply increased compared to the wild type strain (2.25%), and it was further increased in M-2 (60.09%) suggesting a negative role of ACOX in MCFAs production. However, MCFAs in M-3 were much decreased compared to M-1,suggesting a positive role of ACOT in MCFAs production. The M-2 strain showed maximum lipid productivity (~1800 milligram per liter per day or mg/L.d) and MCFAs productivity (~1100 mg/L.d). Taken together, this study elaborates on how the combination of two multidimensional approaches, TE gene over-expression and modification of the β-oxidation pathway via substantial knockout of specific ACOX gene, significantly increased the production of MCFAs. This synergistic approach ultimately offers a novel opportunity for synthetic/industrial biologists to increase the content of MCFAs.

Project description:BackgroundSarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.ObjectiveTo investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosis METHODS: We retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case-case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.ResultsWe included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11-4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91-12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57-11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46-16.1; close human contact: OR 3.78; 95% CI 1.47-9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28-19.2) or livestock (OR 9.86; 95% CI 1.95-49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33-7.79).ConclusionsOur study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements-hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

Dataset Information

Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis.

Background

Methods

Results

Conclusions

Publications

Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets