RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.
CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
METHODOLOGY: Eight (8) urine and serum samples each obtained from consenting healthy controls (HC), twenty-five (25) urine and serum samples each from first episode treatment naïve MDD (TNMDD) patients, and twenty (22) urine and serum samples each s from treatment naïve MDD patients 2 weeks after SSRI treatment (TWMDD) were analysed for metabolites using proton nuclear magnetic resonance (1HNMR) spectroscopy. The evaluation of patients' samples was carried out using Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Square- Discriminant Analysis (OPLSDA) models.
RESULTS: In the serum, decreased levels of lactate, glucose, glutamine, creatinine, acetate, valine, alanine, and fatty acid and an increased level of acetone and choline in TNMDD or TWMDD irrespective of whether an OPLSDA or PLSDA evaluation was used were identified. A test for statistical validations of these models was successful.
CONCLUSION: Only some changes in serum metabolite levels between HC and TNMDD identified in this study have potential values in the diagnosis of MDD. These changes included decreased levels of lactate, glutamine, creatinine, valine, alanine, and fatty acid, as well as an increased level of acetone and choline in TNMDD. The diagnostic value of these changes in metabolites was maintained in samples from TWMDD patients, thus reaffirming the diagnostic nature of these metabolites for MDD.
Methods: The MRS was performed on 35 IGE patients (26 women and 11 men) with average age of 32 (ranged from 18 to 43) and 35 healthy individuals (13 women and 22 men) with average age of 31 (ranged from 21 to 50) as the control group. The levels of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) were measured using MRS. The NAA/Cr and NAA/Cho ratios were calculated for all participants. These values were statistically compared using t-test between the groups.
Results: The NAA had significant lower values in IGE patients, 9.6 (SD = 0.8) and 9.9 (SD = 0.7) for right and left thalamus, respectively, compared to 10.9 (SD = 0.9) and 10.7 (SD = 0.9) in control group. The Cr values in the left side of thalamus were significantly higher in IGE patients (6.7 [SD = 0.8] versus 5.8 [SD = 0.5]); however, there was no difference in right thalamus. Measurements showed no difference for amounts of Cho between the groups in both sides of thalamus. The NAA/Cr ratio was 1.48 (SD = 0.14) and 1.48 (SD = 0.16) for right and left thalamus, respectively, in IGE patients in comparison with 1.83 (SD = 0.2) and 1.86 (SD = 0.26) in controls. There was no meaningful variation between the NAA/Cho ratio of the right and left thalamus among the groups.
Conclusion: Thalamic NAA, Cr and NAA/Cr ratio values in IGE patients showed statistical differences compared to healthy individuals. Evaluating metabolites variations in thalamus using MRS is suggested for differentiating IGE patients from healthy individuals.
METHODS: 1H-MRS utilising the Single-Voxel Spectroscopy (SVS) technique was performed using a 3.0Tesla MRI on 45 optic radiations (15 from healthy subjects, 15 from mild glaucoma patients, and 15 from severe glaucoma patients). A standardised Volume of Interest (VOI) of 20 × 20 × 20 mm was placed in the region of optic radiation. Mild and severe glaucoma patients were categorised based on the Hodapp-Parrish-Anderson (HPA) classification. Mean and multiple group comparisons for metabolite concentration and metabolite concentration ratio between glaucoma grades and healthy subjects were obtained using one-way ANOVA.
RESULTS: The metabolite concentration and metabolite concentration ratio between the optic radiations of glaucoma patients and healthy subjects did not demonstrate any significant difference (p > 0.05).
CONCLUSION: Our findings show no significant alteration of metabolite concentration associated with neurodegeneration that could be measured by single-voxel 1H-MRS in optic radiation among glaucoma patients.
KEY POINTS: • Glaucoma disease has a neurodegenerative component. • Metabolite changes have been observed in the neurodegenerative process in the brain. • Using SVS, no metabolite changes in optic radiation were attributed to glaucoma.
Methods: 21 day old male Sprague Dawley rats were assigned as Experiment-1 & 2 - PND rats were divided into 4 groups with interventions for 7 months (n = 8/group). NC- Normal control fed normal chow diet; OB- Obese group, fed high fat diet; OB + CHO + DHA- fed high fat diet and oral supplementation of choline, DHA. OB + EE- fed high fat diet along with exposure to enriched environment .Experiment-2 had similar groups and interventions as experiment 1 but for next 5 months were fed normal chow diet without any interventions. Body mass index was assessed and blood was analyzed for serum lipid profile. Common Carotid Artery (CCA) was processed for Haematoxylin and eosin, Verhoff Vangeison stains. Images of tissue sections were analyzed and quantified using image J and tissue quant software.
Results: In experiment.1, mean body mass index (p