Comprehensive lipid profiles investigation reveals host metabolic and immune alterations during anti-tuberculosis treatment: Implications for therapeutic monitoring

Anh, Nguyen Ky; Phat, Nguyen Ky; Yen, Nguyen Thi Hai; Jayanti, Rannissa Puspita; Thu, Vo Thuy Anh; Park, Young Jin; Cho, Yong‐Soon; Shin, Jae‐Gook; Kim, Dong Hyun; Oh, Jee Youn; Long, Nguyen Phuoc

doi:10.1016/j.biopha.2022.114187

Cited by 13 publications

(14 citation statements)

References 43 publications

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“…However, individual biomarkers reported in our work could be strong candidates to be considered when establishing a biosignature that takes into account the metabolic alterations during TB treatment. We provided proof-of-concept results regarding the potential of lipid biomarkers (27). These findings collectively demonstrate that metabolism-centric biomarkers could be a significant aspect to be explored further in addition to approaches targeting immunological processes.…”

Section: Discussionmentioning

confidence: 66%

“…Among the genes involved in these pathways, 162 non-overlapped lipid-related genes potentially associated with the pathophysiology of TB were extracted and validated in three datasets (26). Our other study of the plasma lipidome of patients with TB during the 6-month treatment regimen showed changes in pathways related to lipid metabolism and the host immune response (27). These findings suggest an association between systemic lipid alterations and TB disease status.…”

Section: Introductionmentioning

confidence: 52%

“…Furthermore, ACSL4 was found to be overexpressed in anti-TB drug-induced liver injury, indicating ferroptosis induction during anti-TB treatment (85). PLD4 is differentially expressed in patients with TB (27). Phospholipase D activation is associated closely with Mtb phagocytosis by macrophages (86).…”

Section: Discussionmentioning

confidence: 99%

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Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers

Phat,

Tien,

Anh

et al. 2023

Front. Immunol.

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BackgroundThe optimal diagnosis and treatment of tuberculosis (TB) are challenging due to underdiagnosis and inadequate treatment monitoring. Lipid-related genes are crucial components of the host immune response in TB. However, their dynamic expression and potential usefulness for monitoring response to anti-TB treatment are unclear. MethodologyIn the present study, we used a targeted, knowledge-based approach to investigate the expression of lipid-related genes during anti-TB treatment and their potential use as biomarkers of treatment response. Results and discussionThe expression levels of 10 genes (ARPC5, ACSL4, PLD4, LIPA, CHMP2B, RAB5A, GABARAPL2, PLA2G4A, MBOAT2, and MBOAT1) were significantly altered during standard anti-TB treatment. We evaluated the potential usefulness of this 10-lipid-gene signature for TB diagnosis and treatment monitoring in various clinical scenarios across multiple populations. We also compared this signature with other transcriptomic signatures. The 10-lipid-gene signature could distinguish patients with TB from those with latent tuberculosis infection and non-TB controls (area under the receiver operating characteristic curve > 0.7 for most cases); it could also be useful for monitoring response to anti-TB treatment. Although the performance of the new signature was not better than that of previous signatures (i.e., RISK6, Sambarey10, Long10), our results suggest the usefulness of metabolism-centric biomarkersConclusionsLipid-related genes play significant roles in TB pathophysiology and host immune responses. Furthermore, transcriptomic signatures related to the immune response and lipid-related gene may be useful for TB diagnosis and treatment monitoring.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 52%

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Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers

Phat,

Tien,

Anh

et al. 2023

Front. Immunol.

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“…A case–control study using unbiased lipid omics confirmed that oxylipins, cholesteryl esters, ceramides, sphingomyelins, diacylglycerol and triacylglycerol are associated with TB treatment failure [ 33 ]. UPLC-QToF MS revealed that cholesterol ester (CE), monoacylglycerols, and phosphatidylcholine (PC) were associated with host immune responses in active TB patients [ 34 ]. Han et al [ 35 ] speculated that M. tuberculosis infection may regulate lipid metabolism in TB patients and may promote host-assisted bacterial degradation of phospholipids and the accumulation of cholesterol esters.…”

Section: Discussionmentioning

confidence: 99%

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study

Du,

Ren,

Wang

et al. 2024

Eur J Med Res

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Background Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. Method Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene–exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. Results According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484–5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140–14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269–5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028–0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040–1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035–1.841, P = 0.028) were directly correlated with the occurrence of PTB. Conclusions This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

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“…Horizontal (metabolomics and lipidomics) and vertical (genomics, transcriptomics, proteomics, and metabolomics) multi-omics data integration present a powerful approach to capture a holistic view of the molecular landscape, which could provide a comprehensive understanding of an individual's response to anti-TB drugs [ 123 , 124 ]. These approaches are described as prospects to improve the better-personalized medicine of TB and allow the discovery of biosignatures for treatment monitoring and clinical outcomes (efficacy and AEs) [ 123 , [125] , [126] , [127] ]. Long et al.…”

Section: Six Primary Prospects In Tb Clinical Managementmentioning

confidence: 99%

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

Thu,

Tien,

Yen

et al. 2024

Journal of Pharmaceutical Analysis

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Comprehensive lipid profiles investigation reveals host metabolic and immune alterations during anti-tuberculosis treatment: Implications for therapeutic monitoring

Cited by 13 publications

References 43 publications

Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers

Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

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