Biomarkers intersect with the exposome

Rappaport, Stephen M.

doi:10.3109/1354750x.2012.691553

Cited by 107 publications

(110 citation statements)

References 66 publications

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“…127 Newer investigational techniques use broader net and more global non-targeted strategies, like genomics, proteomics, and metabolomics for identifying multiple biomarkers in tissues from normal and disease affected individuals. [137][138][139][140][141] Metabolomic evaluations of plasma generated set of metabolites (indicators) are capable of differentiating between PD patients and controls irrespective of medication status. 142 Recently a study using cerebrospinal fluid and serum of PD affected patients using thorough pathological assessments has shown that these cell free peripheral fluid profiles provide an accurate picture of the cell level pathological events in the deceased tissue of PD patients.…”

Section: Future Directions For Reliable Early Non-invasive Biomarkersmentioning

confidence: 99%

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Nair

Ramachandran

Joghee

et al. 2018

J Neurogastroenterol Motil

118

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Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients.

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Section: Future Directions For Reliable Early Non-invasive Biomarkersmentioning

confidence: 99%

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Nair

Ramachandran

Joghee

et al. 2018

J Neurogastroenterol Motil

118

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“…Despite this, acute phase proteins such as C-reactive protein (CRP), fecal calprotectin in addition to the erythrocyte sedimentation rate (ESR) and other clinical activity indicators are more typically used in practice to monitor disease progression in addition to colonoscopy (11). Unbiased discovery in patient plasma samples has the potential to capture both the reactive pathways that result in symptoms as well as identify novel causal proteins that may have initiated disease onset and the biological switch to autoimmune complications of IBD (12,13). The regulation of homeostasis between the intestinal epithelial cells, mucosal surface, and the immune system that contribute to exacerbated inflamed response are less well characterized and would benefit from the posteriori knowledge of the global "omics" approach to explore emerging causal and reactive proteins and peptides for further validation.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective

Wasinger

Yau

Duo

et al. 2016

Molecular & Cellular Proteomics

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Breakdown of the protective gut barrier releases effector molecules and degradation products into the blood stream making serum and plasma ideal as a diagnostic medium. The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring inflammatory bowel disease (IBD) activity, that is less invasive than colonoscopy. Differences in the enriched low mass plasma proteome (<25 kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and "Tier-2" FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by multiple reaction monitoring in plasma and serum including both inflammatory; rheumatoid arthritis controls, and non-inflammatory healthy controls; ulcerative colitis (UC), and Crohn's disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in plasma. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Peptides differentiating controls from IBD originate from secreted phosphoprotein 24 (SPP24, p ‫؍‬ 0.000086, 0.009); whereas those in remission and healthy can be differentiated in UC by SPP24 (p ‫؍‬ 0.00023, 0.001), ␣-1-microglobulin (AMBP, p ‫؍‬ 0.006) and CD by SPP24 (p ‫؍‬ 0.019, 0.05). UC and CD can be differentiated by Guanylin (GUC2A, p ‫؍‬ 0.001), and Secretogranin-1 (CHGB p ‫؍‬ 0.035). Active and quiescent disease can also be differentiated in UC and CD by CHGB (p < 0.023) SPP24 (p < 0.023) and AMBP (UC p ‫؍‬ 0.046). Five peptides discriminating IBD activity and severity had very little-to-no correlation to erythrocyte sedimentation rate, C-reactive protein, white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These proteins have the potential to improve diagnosis and evaluate IBD activity, reducing the need for more invasive techniques. Data are available via ProteomeXchange with identifier

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“…Of course, even under the most controlled conditions, humans experience highly variable mixtures of exposures from the natural and man-made environment. Considering this complexity has garnered enthusiasm in light of the growing technologies and field of 'exposome research' although this has yet to be rigorously applied to epigenetic studies (Buck Louis et al, 2013;Rappaport, 2012;Wild et al, 2013).…”

Section: Additional Factors Influencing Epigeneticsmentioning

confidence: 99%

Influence of environmental exposure on human epigenetic regulation

Marsit

2015

Journal of Experimental Biology

191

119

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Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus of a number of studies and its detoxification mechanisms are well understood. Importantly, the tissues and cells being examined must be considered in context in order to interpret the findings of these studies. For example, by studying the placenta, it is possible to identify potential epigenetic adaptations of key genes and pathways that may alter the developmental course in line with the developmental origins of health and disease paradigm. Alternatively, studies of newborn cord blood can be used to examine how environmental exposure in utero can impact the composition of cells within the peripheral blood, leading to immunological effects of exposure. The results suggest that in humans, like other vertebrates, there is a susceptibility for epigenomic alteration by the environment during intrauterine development, and this may represent a mechanism of plasticity of the organism in response to its environment as well as a mechanism through which long-term health consequences can be shaped.

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Biomarkers intersect with the exposome

Cited by 107 publications

References 66 publications

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective

Influence of environmental exposure on human epigenetic regulation

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