Metabolic Insights into HIV/TB Co-infection: An Untargeted Urinary Metabolomics Approach
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ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1397 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:IntroductionAmid the global health crisis, HIV/TB co-infection presents significant challenges, amplifying the burden on patients and healthcare systems alike. Metabolomics offers an innovative window into the metabolic disruptions caused by co-infection, potentially improving diagnosis and treatment monitoring.AimThis study uses untargeted metabolomics to investigate the urinary metabolic signature of HIV/TB co-infection, enhancing understanding of the metabolic interplay between these infections.MethodsUrine samples from South African adults, categorised into four groups - healthy controls, TB-positive, HIV-positive, and HIV/TB co-infected - were analysed using GCxGC-TOFMS. Metabolites showing significant differences among groups were identified through Kruskal-Wallis and Wilcoxon rank sum tests.ResultsVarious metabolites (n = 23) were modulated across the spectrum of health and disease states represented in the cohorts. The metabolomic profiles reflect a pronounced disruption in biochemical pathways involved in energy production, amino acid metabolism, gut microbiome, and the immune response, suggesting a bidirectional exacerbation between HIV and TB. While both diseases independently perturb the host's metabolism, their co-infection leads to a unique metabolic phenotype, indicative of an intricate interplay rather than a simple additive effect.ConclusionMetabolic profiling revealed a unique metabolic landscape shaped by HIV/TB co-infection. The findings highlight the potential of urinary differential metabolites for co-infection, offering a non-invasive tool for enhancing diagnostic precision and tailoring therapeutic interventions. Future research should focus on expanding sample sizes and integrating longitudinal analyses to build upon these foundational insights, paving the way for metabolomic applications in combating these concurrent pandemics.
| S-EPMC11252185 | biostudies-literature
Project description: Not available
| S-BSST1402 | biostudies-other
Project description: Not available
| S-BSST1084 | biostudies-other
Project description:BackgroundThe synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease.MethodsIn this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions.ResultsHIV/TB co-infection induced significant changes to the host's lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls.ConclusionThis study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.
| S-EPMC10436461 | biostudies-literature
Project description:Zika virus (ZIKV), an emerging virus belonging to the Flaviviridae family, causes severe neurological clinical complications and has been associated with Guillain-Barré syndrome, fetal abnormalities known collectively as congenital Zika syndrome, and microcephaly. Studies have shown that ZIKV infection can alter cellular metabolism, directly affecting neural development. Brain growth requires controlled cellular metabolism, which is essential for cell proliferation and maturation. However, little is known regarding the metabolic profile of ZIKV-infected newborns and possible associations related to microcephaly. Furthering the understanding surrounding underlying mechanisms is essential to developing personalized treatments for affected individuals. Thus, metabolomics, the study of the metabolites produced by or modified in an organism, constitutes a valuable approach in the study of complex diseases. Here, 26 serum samples from ZIKV-positive newborns with or without microcephaly, as well as controls, were analyzed using an untargeted metabolomics approach involving gas chromatography-mass spectrometry (GC-MS). Significant alterations in essential and non-essential amino acids, as well as carbohydrates (including aldohexoses, such as glucose or mannose) and their derivatives (urea and pyruvic acid), were observed in the metabolic profiles analyzed. Our results provide insight into relevant metabolic processes in patients with ZIKV and microcephaly.
| S-EPMC8070065 | biostudies-literature
Project description:Understanding the root causes of neuronal vulnerability to ischemia is paramount to the development of new therapies for stroke. Transient global cerebral ischemia (tGCI) leads to selective neuronal cell death in the CA1 sub-region of the hippocampus, while the neighboring CA3 sub-region is left largely intact. By studying factors pertaining to such selective vulnerability, we can develop therapies to enhance outcome after stroke. Using untargeted liquid chromatography-mass spectrometry, we analyzed temporal metabolomic changes in CA1 and CA3 hippocampal areas following tGCI in rats till the setting of neuronal apoptosis. 64 compounds in CA1 and 74 in CA3 were found to be enriched and statistically significant following tGCI. Pathway analysis showed that pyrimidine and purine metabolism pathways amongst several others to be enriched after tGCI in CA1 and CA3. Metabolomics analysis was able to capture very early changes following ischemia. We detected 6 metabolites to be upregulated and 6 to be downregulated 1 hour after tGCI in CA1 versus CA3. Several metabolites related to apoptosis and inflammation were differentially expressed in both regions after tGCI. We offer a new insight into the process of neuronal apoptosis, guided by metabolomic profiling that was not performed to such an extent previously.
| S-EPMC7162929 | biostudies-literature
Project description:BackgroundTB and HIV co-epidemic is a major public health problem in many parts of the world, particularly in developing counties. We aimed to summarize the prevalence of TB and HIV co-infection in mainland China, using meta-analysis based on systematic review of published articles.MethodsWe systematically reviewed published studies, from the MEDLINE and Chinese BioMedical Literature Databases, on the prevalence of HIV infection among TB patients and on the prevalence of TB among HIV/AIDS population until 15 April 2010, and quantitatively summarized the estimates using meta-analysis.ResultsIn total, 29 studies were included in this review, with consistently homogeneous results. TB patients, for whom the summary prevalence of HIV infection was 0.9% (0.6%-1.4%) in mainland China, were found to be a potential target population for HIV screening. The prevalence of TB among HIV/AIDS population was 7.2% (4.2%-12.3%), but this was much higher when the analyses were restricted to AIDS patients (22.8%). Significantly higher prevalence was observed for males and hospital-based studies.ConclusionsOur analyses indicated that the prevalence of HIV/TB co-infection in China deserves special attention, screening of TB among HIV/AIDS populations should be attached more importance, which would be much more helpful for treatment of both diseases.
| S-EPMC2873981 | biostudies-literature
Project description:Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) which is the main cause of vision loss in the working-age population. Currently known risk factors such as age, disease duration, and hemoglobin A1c lack sufficient efficiency to distinguish patients with early stages of DR. A total of 194 plasma samples were collected from patients with type 2 DM and DR (moderate to proliferative (PDR) or control (no or mild DR) matched for age, gender, diabetes duration, HbA1c, and hypertension. Untargeted lipidomic and metabolomic approaches were performed. Partial-least square methods were used to analyze the datasets. Levels of 69 metabolites and 85 lipid species were found to be significantly different in the plasma of DR patients versus controls. Metabolite set enrichment analysis indicated that pathways such as metabolism of branched-chain amino acids (methylglutaryl carnitine p = 0.004), the kynurenine pathway (tryptophan p < 0.001), and microbiota metabolism (p-Cresol sulfate p = 0.004) were among the most enriched deregulated pathways in the DR group. Moreover, Glucose-6-phosphate (p = 0.001) and N-methyl-glutamate (p < 0.001) were upregulated in DR. Subgroup analyses identified a specific signature associated with PDR, macular oedema, and DR associated with chronic kidney disease. Phosphatidylcholines (PCs) were dysregulated, with an increase of alkyl-PCs (PC O-42:5 p < 0.001) in DR, while non-ether PCs (PC 14:0-16:1, p < 0.001; PC 18:2-14:0, p < 0.001) were decreased in the DR group. Through an unbiased multiomics approach, we identified metabolites and lipid species that interestingly discriminate patients with or without DR. These features could be a research basis to identify new potential plasma biomarkers to promote 3P medicine.
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Project description:Oncogene-associated metabolic signatures in prostate cancer, identified by an integrative analysis of cultured cells and murine and human tumors, suggest that AKT activation results in a glycolytic phenotype whereas MYC induces aberrant lipid metabolism. Heterogeneity in human tumors makes this simplistic interpretation obtained from experimental models more challenging. Metabolic reprogramming as a function of distinct molecular aberrations has major diagnostic and therapeutic implications.
| S-EPMC4905328 | biostudies-other
Project description:Metabolomics studies of the early-life exposome often use maternal urine specimens to investigate critical developmental windows, including the periconceptional period and early pregnancy. During these windows changes in kidney function can impact urine concentration. This makes accounting for differential urinary dilution across samples challenging. Because there is no consensus on the ideal normalization approach for urinary metabolomics data, this study's objective was to determine the optimal post-analytical normalization approach for untargeted metabolomics analysis from a periconceptional cohort of 45 women. Urine samples consisted of 90 paired pre- and post-implantation samples. After untargeted mass spectrometry-based metabolomics analysis, we systematically compared the performance of three common approaches to adjust for urinary dilution-creatinine adjustment, specific gravity adjustment, and probabilistic quotient normalization (PQN)-using unsupervised principal components analysis, relative standard deviation (RSD) of pooled quality control samples, and orthogonal partial least-squares discriminant analysis (OPLS-DA). Results showed that creatinine adjustment is not a reliable approach to normalize urinary periconceptional metabolomics data. Either specific gravity or PQN are more reliable methods to adjust for urinary concentration, with tighter quality control sample clustering, lower RSD, and better OPLS-DA performance compared to creatinine adjustment. These findings have implications for metabolomics analyses on urine samples taken around the time of conception and in contexts where kidney function may be altered.
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