Browsing by Author "Lu, Peiran"

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    Comment on Liu et al. Aberrant Expression of FBXO2 Disrupts Glucose Homeostasis Through Ubiquitin-Mediated Degradation of Insulin Receptor in Obese Mice. Diabetes 2017;66:689–698
    (American Diabetes Association, 2020-02) Wong, Siauyen; Nelson, Rick F.; Lu, Peiran; Paulson, Henry; Lin, Dingbo; Otolaryngology -- Head and Neck Surgery, School of Medicine
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    Xanthophylls Shift the Gut Microbiota and Reduce Inflammation in Mice During Influenza A Virus Infection
    (Elsevier, 2021) Lu, Peiran; Wong, Siau Yen; Chai, Jianmin; Wu, Lei; Smith, Brenda; Lucas, Edralin; Clarke, Stephen L.; Chowanadisai, Winyoo; He, Hui; Zhao, Jiangchao; Conway, Tyrrell; Wyss, Adrian; Lin, Dingbo; Obstetrics and Gynecology, School of Medicine
    Objectives: Seasonal influenza A virus (IAV) infection impacts both respiratory and intestinal microbiome homeostasis. However, it is not well understood the extent to which the gut-lung axis plays the role in innate immunity and acute inflammation during IAV. Xanthophylls are fat-soluble, oxygenized carotenoids with potent antioxidant properties. We recently reported that xanthophylls can promote gut microbiome homeostasis and is associated with attenuation of intestinal and systemic inflammation. Here, we sought to investigate the protective effects of xanthophylls, e.g., zeaxanthin (Z) and astaxanthin (A) in IAV pneumonia by regulation of the host gut microbiome. Methods: Six-week-old male and female 129S6 wild type (WT) and beta-carotene oxygenase 2 (BCO2) knockout mice were fed with AIN93M chow diets supplemented with or without Z (0.02% w/w) and A (0.02 w/w) (e.g., A + Z). After 6 weeks of the dietary intervention, mice were intranasally infected with 100 pfu H1N1 PR8 virus. Animal body weight and phenotypes were monitored daily. Animals were sacrificed 6 days post-infection. Blood and lung tissues were collected for experiments. H & E staining, gut microbiota 16S rRNA sequencing, immunohistochemistry, and immunoblotting were used for clinical, histopathological, and other biochemical assessments. Results: Depletion of BCO2, the xanthophyll cleavage enzyme, made mice more resistant to IAV infection. Administration of A + Z caused A + Z accumulation and enhanced resistance to IAV in BCO2 KO but not WT mice, as demonstrated by histological lung damage and colon and ileum inflammation. Gut microbiome profiling results showed that α–diversity and β–diversity were significantly altered in these experimental groups. In particular, A + Z accumulation is positively associated with Bacteroides abundance. The increases in Bacteroides abundance were even greater in BCO2 KO mice, compared to the WT. Furthermore, Akkermansia abundance was significantly increased in BCO2 KO mice after IAV infection. Conclusions: Association of xanthophyll accumulation with the gut microbiota shift could protect animals from IAV infection by reducing local inflammation. Bacteroides potentially plays a beneficial role in this process.
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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.