Browsing by Author "Jasbi, Paniz"

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    Targeted metabolomics reveals plasma biomarkers and metabolic alterations of the aging process in healthy young and older adults
    (Springer, 2023) Jasbi, Paniz; Nikolich‑Žugich, Janko; Patterson, Jeffrey; Knox, Kenneth S.; Jin, Yan; Weinstock, George M.; Smith, Patricia; Twigg, Homer L., III; Gu, Haiwei; Medicine, School of Medicine
    With the exponential growth in the older population in the coming years, many studies have aimed to further investigate potential biomarkers associated with the aging process and its incumbent morbidities. Age is the largest risk factor for chronic disease, likely due to younger individuals possessing more competent adaptive metabolic networks that result in overall health and homeostasis. With aging, physiological alterations occur throughout the metabolic system that contribute to functional decline. In this cross-sectional analysis, a targeted metabolomic approach was applied to investigate the plasma metabolome of young (21-40y; n = 75) and older adults (65y + ; n = 76). A corrected general linear model (GLM) was generated, with covariates of gender, BMI, and chronic condition score (CCS), to compare the metabolome of the two populations. Among the 109 targeted metabolites, those associated with impaired fatty acid metabolism in the older population were found to be most significant: palmitic acid (p < 0.001), 3-hexenedioic acid (p < 0.001), stearic acid (p = 0.005), and decanoylcarnitine (p = 0.036). Derivatives of amino acid metabolism, 1-methlyhistidine (p = 0.035) and methylhistamine (p = 0.027), were found to be increased in the younger population and several novel metabolites were identified, such as cadaverine (p = 0.034) and 4-ethylbenzoic acid (p = 0.029). Principal component analysis was conducted and highlighted a shift in the metabolome for both groups. Receiver operating characteristic analyses of partial least squares-discriminant analysis models showed the candidate markers to be more powerful indicators of age than chronic disease. Pathway and enrichment analyses uncovered several pathways and enzymes predicted to underlie the aging process, and an integrated hypothesis describing functional characteristics of the aging process was synthesized. Compared to older participants, the young group displayed greater abundance of metabolites related to lipid and nucleotide synthesis; older participants displayed decreased fatty acid oxidation and reduced tryptophan metabolism, relative to the young group. As a result, we offer a better understanding of the aging metabolome and potentially reveal new biomarkers and predicted mechanisms for future study.
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    Zeaxanthin Drives Dynamic Changes in the Mouse Metabolome Through Gut Microbiome Shift
    (Elsevier, 2021) Lu, Peiran; Wong, Siau Yen; Chai, Jianmin; Jasbi, Paniz; Wu, Lei; Lyu, Yi; Tang, Minghua; Smith, Brenda; Lucas, Edralin; Clarke, Stephen L.; Chowanadisai, Winyoo; Shen, Xinchun; He, Hui; Zhao, Jiangchao; Gu, Haiwei; Conway, Tyrrell; Wyss, Adrian; Lin, Dingbo; Obstetrics and Gynecology, School of Medicine
    Objectives: Zeaxanthin, an oxygenized carotenoid, exerts antioxidant properties in human nutrition and metabolism. Like other carotenoids, zeaxanthin is poorly absorbed in the small intestine. The large portion of zeaxanthin reaches the colon and is not fully recovered in the colon. In this study, we aimed to investigate the association of zeaxanthin intake with the gut microbiome homeostasis and metabolomic responses in mice. Methods: Six-week-old male and female C57BL/6J wild type (WT), beta-carotene oxygenase 2 (BCO2) knockout mice were fed with AIN93M chow diets supplemented with or without zeaxanthin (0.02% w/w) for 10 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Cecal contents, colon, serum, feces, and other tissues were collected for laboratory assessments.16S rRNA sequencing and LC-MS/MS were performed for gut microbiota profiling and serum and fecal metabolomics analysis, respectively. Results: Significant zeaxanthin accumulation occurred in BCO2 KO, but not WT mice. Zeaxanthin accumulation was associated with the alteration of colonic gut microbiota composition, for example, zeaxanthin-increased abundance in Lachnospiraceae, Proteobacteria, and Parabacteroides, indicating enhanced short-chain production, improved intestinal integrity, and anaerobic bacterial colonization. The results of fecal and serum metabolomics revealed that zeaxanthin significantly altered tyrosine metabolism, branched-chain fatty acid oxidation, fatty acid biosynthesis, and phospholipid biosynthesis, and suppressed levels of kynurenine and trimethylamine N-oxide (TMAO). Conclusions: The results suggested that zeaxanthin accumulation promotes gut microbiome homeostasis and alters the gut microbial metabolites as signals in stimulating the host-gut microbe interplay.