17 research outputs found
Key Role for the 12-Hydroxy Group in the Negative Ion Fragmentation of Unconjugated C24 Bile Acids
Host-gut microbial
interactions contribute to human health and
disease states and an important manifestation resulting from this
cometabolism is a vast diversity of bile acids (BAs). There is increasing
interest in using BAs as biomarkers to assess the health status of
individuals and, therefore, an increased need for their accurate separation
and identification. In this study, the negative ion fragmentation
behaviors of C24 BAs were investigated by UPLC-ESI-QTOF-MS. The step-by-step
fragmentation analysis revealed a distinct fragmentation mechanism
for the unconjugated BAs containing a 12-hydroxyl group. The unconjugated
BAs lacking 12-hydroxylation fragmented via dehydration and dehydrogenation.
In contrast, the 12-hydroxylated ones, such as deoxycholic acid (DCA)
and cholic acid (CA), employed dissociation routes including dehydration,
loss of carbon monoxide or carbon dioxide, and dehydrogenation. All
fragmentations of the 12-hydroxylated unconjugated BAs, characterized
by means of stable isotope labeled standards, were associated with
the rotation of the carboxylate side chain and the subsequent rearrangements
accompanied by proton transfer between 12-hydroxyl and 24-carboxyl
groups. Compared to DCA, CA underwent further cleavages of the steroid
skeleton. Accordingly, the effects of stereochemistry on the fragmentation
pattern of CA were investigated using its stereoisomers. Based on
the knowledge gained from the fragmentation analysis, a novel BA,
3β,7β,12α-trihydroxy-5β-cholanic acid, was
identified in the postprandial urine samples of patients with nonalcoholic
steatohepatitis. The analyses used in this study may contribute to
a better understanding of the chemical diversity of BAs and the molecular
basis of human liver diseases that involve BA synthesis, transport,
and metabolism
Tryptophan Predicts the Risk for Future Type 2 Diabetes
<div><p>Recently, 5 amino acids were identified and verified as important metabolites highly associated with type 2 diabetes (T2D) development. This report aims to assess the association of tryptophan with the development of T2D and to evaluate its performance with existing amino acid markers. A total of 213 participants selected from a ten-year longitudinal Shanghai Diabetes Study (SHDS) were examined in two ways: 1) 51 subjects who developed diabetes and 162 individuals who remained metabolically healthy in 10 years; 2) the same 51 future diabetes and 23 strictly matched ones selected from the 162 healthy individuals. Baseline fasting serum tryptophan concentrations were quantitatively measured using ultra-performance liquid chromatography triple quadruple mass spectrometry. First, serum tryptophan level was found significantly higher in future T2D and was positively and independently associated with diabetes onset risk. Patients with higher tryptophan level tended to present higher degree of insulin resistance and secretion, triglyceride and blood pressure. Second, the prediction potential of tryptophan is non-inferior to the 5 existing amino acids. The predictive performance of the combined score improved after taking tryptophan into account. Our findings unveiled the potential of tryptophan as a new marker associated with diabetes risk in Chinese populations. The addition of tryptophan provided complementary value to the existing amino acid predictors.</p></div
ROCs of 5AAs-combined score and 6-AAs combined score in discriminating a) T2D and matched NGT (n = 74); and b) T2D and NGT (n = 213).
<p>ROCs of 5AAs-combined score and 6-AAs combined score in discriminating a) T2D and matched NGT (n = 74); and b) T2D and NGT (n = 213).</p
Additional file 16: Table S10. of Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice
Feed ingredients. (XLSX 10 kb
Baseline clinical characteristics and tryptophan levels in individuals who developed diabetes (T2D, n = 51) and remained metabolically healthy (NGT, n = 162) in 10 years, and in matched future metabolically healthy (matched NGT, n = 23) individuals.
<p>Baseline clinical characteristics and tryptophan levels in individuals who developed diabetes (T2D, n = 51) and remained metabolically healthy (NGT, n = 162) in 10 years, and in matched future metabolically healthy (matched NGT, n = 23) individuals.</p
a) Baseline tryptophan levels (mean with S.E.) in future NGT (n = 162), matched future NGT (n = 23), and future T2D (n = 51) groups. b) Association of tryptophan with metabolic markers in all participants (n = 213).
<p><b>Abbreviations:</b> BMI = body mass index; Glucose0 = fasting plasma glucose; Glucose120 = 2 h plasma glucose; INS0 = fasting insulin; INS120 = 2 h insulin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; SP = systolic blood pressure; DP = diastolic blood pressure; TC = total cholesterol; TG = total triglycerides; HOMA-IR = homeostatic model assessment of insulin resistance (FPG*INS0/22.5); Matsuda index = 10000/(Glucose0×INS0×Glucose120×INS120)<sup>0.5</sup>; HOMA-Beta = homeostatic model assessment of beta-cell function (20*INS0/(Glucose0-3.5); First-phase secretion = 2032+4.681*INS0-135*Glucose120+0.995*INS120+27.99*BMI-269.1*Glucose0; Second-phase secretion = 277+0.8*INS0-42.79*Glucose120+0.321*INS120+5.338*BMI.</p
Additional file 11: Figure S4. of Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice
The trajectories of bile acids and microbiome alteration along 56Â days in control and HFD groups. (DOC 167 kb
Additional file 6: Figure S2. of Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice
The microbial community diversity in control and HFD groups shown by Simpson reciprocal index. (DOC 54 kb
Additional file 12: Table S8. of Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice
Time dependent alteration of bile acids and microbes in control and HFD groups. (XLSX 33 kb