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Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD, we sequenced the gut metagenomes of patients with AMD and controls. The genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum were relatively enriched in patients with AMD, whereas Bacteroides eggerthii was enriched in controls. Patient's intestinal microbiomes were enriched in genes of the L-alanine fermentation, glutamate degradation and arginine biosynthesis pathways and decreased in genes of the fatty acid elongation pathway. These findings suggest that modifications in the intestinal microbiome are associated with AMD, inferring that this common sight threatening disease may be targeted by microbiome-altering interventions.

SUBMITTER: Zinkernagel MS

PROVIDER: S-EPMC5240106 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration.

Zinkernagel Martin S MS Zysset-Burri Denise C DC Keller Irene I Berger Lieselotte E LE Leichtle Alexander B AB Largiadèr Carlo R CR Fiedler Georg M GM Wolf Sebastian S

Scientific reports 20170117

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD ...[more]

PMID: 28094305

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Project description:PurposeTo determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD) and similarly-aged controls.MethodsMetabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape.ResultsOf the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05). A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism.ConclusionsThese data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can provide further insight into the pathophysiology of AMD.

Project description:Although the triggers causing angiogenesis in the context of neovascular age-related macular degeneration (nAMD) are not fully understood, oxidative stress is likely involved. Oxidative stress in the eye can occur through exposure of macular tissues to sunlight and local or systemic exposure to oxidative stressors associated with environmental or lifestyle factors. Because trace elements have been implicated as regulators of oxidative stress and cellular antioxidant defense mechanisms, we hypothesized that they may play a role as a risk factor, modifying the progression toward nAMD. Herein, we determined whether levels of human plasma trace elements are different in 236 individuals with nAMD compared to 236 age-matched controls without AMD. Plasma levels of 16 trace elements including arsenic, barium, calcium, cadmium, cobalt, chromium, copper, iron, magnesium, manganese, molybdenum, lead, antimony, selenium, vanadium and zinc were measured using inductively coupled plasma mass spectrometry. Associations of trace elements with demographic, environmental and lifestyle factors and AMD-associated genetic variants were assessed. Elevated levels of barium and cadmium and reduced levels of chromium were observed in nAMD patients compared to controls. Mean plasma concentrations of barium were 1.35 μg/L (standard deviation [SD] 0.71) in nAMD and 1.15 μg/L (SD 0.63) in controls (P = 0.001). Mean levels of chromium were 0.37 μg/L (SD 0.22) in nAMD and 0.46 μg/L (SD 0.34) in controls (P = 0.001). Median levels for cadmium, which were not normally distributed, were 0.016 μg/L (interquartile range [IQR] 0.001-0.026) in nAMD and 0.012 μg/L (IQR 0.001-0.022) in controls (P = 0.002). Comparison of the Spearman's correlation coefficients between nAMD patients and controls identified a difference in correlations for 8 trace elements. Cadmium levels were associated with the smoking status (P < 0.001), while barium levels showed a trend of association with the usage of antihypertensive drugs. None of the AMD-associated genetic variants were associated with any trace element levels. In conclusion, in this case-control study we detected elevated plasma levels of barium and cadmium and reduced plasma levels of chromium in nAMD patients. An imbalance in plasma trace elements, which is most likely driven by environmental and lifestyle factors, might have a role in the pathogenesis of AMD. These trace elements may be incorporated as biomarkers into models for prediction of disease risk and progression. Additionally, population-based preventive strategies to decrease Cd exposure, especially by the cessation of smoking, could potentially reduce the burden of nAMD. Future studies are warranted to investigate whether supplementation of Cr would have a beneficial effect on nAMD.

Dataset Information

Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration.

Publications

Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration.

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