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2. The Roles of Gut Microbiome and Plasma Metabolites in the Associations between ABO Blood Groups and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Author

Li-Gao, Ruifang, Grubbs, Kirk, Bertoni, Alain G, Hoffman, Kristi L, Petrosino, Joseph F, Ramesh, Gautam, Wu, Martin, Rotter, Jerome I, Chen, Yii-Der Ida, Evans, Anne M, Robinson, Richard J, Sommerville, Laura, Mook-Kanamori, Dennis, Goodarzi, Mark O, Michelotti, Gregory A, and Sheridan, Patricia A

Subjects
Medical Biochemistry and Metabolomics, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Human Genome, Genetics, Diabetes, Metabolic and endocrine, insulin homeostasis, ABO blood type, metabolites, gut microbiome, mediation analysis, Analytical Chemistry, Clinical Sciences, Biochemistry and cell biology, Medical biochemistry and metabolomics, Analytical chemistry
Abstract

Non-O blood groups are associated with decreased insulin sensitivity and risk of type 2 diabetes. A recent study pinpointed the associations between ABO blood groups and gut microbiome, which may serve as potential mediators for the observed increased disease risks. We aimed to characterize associations between ABO haplotypes and insulin-related traits as well as potential mediating pathways. We assessed insulin homeostasis in African Americans (AAs; n = 109) and non-Hispanic whites (n = 210) from the Microbiome and Insulin Longitudinal Evaluation Study. The ABO haplotype was determined by six SNPs located in the ABO gene. Based on prior knowledge, we included 21 gut bacteria and 13 plasma metabolites for mediation analysis. In the white study cohort (60 ± 9 years, 42% male), compared to the O1 haplotype, A1 was associated with a higher Matsuda insulin sensitivity index, while a lower relative abundance of Bacteroides massiliensis and lactate levels. Lactate was a likely mediator of this association but not Bacteroides massiliensis. In the AAs group (57 ± 8 years, 33% male), we found no association between any haplotype and insulin-related traits. In conclusion, the A1 haplotype may promote healthy insulin sensitivity in non-Hispanic whites and lactate likely play a role in this process but not selected gut bacteria.

Published
2022

3. Rare and common genetic determinants of metabolic individuality and their effects on human health

Author

Surendran, Praveen, Stewart, Isobel D., Au Yeung, Victoria P. W., Pietzner, Maik, Raffler, Johannes, Wörheide, Maria A., Li, Chen, Smith, Rebecca F., Wittemans, Laura B. L., Bomba, Lorenzo, Menni, Cristina, Zierer, Jonas, Rossi, Niccolò, Sheridan, Patricia A., Watkins, Nicholas A., Mangino, Massimo, Hysi, Pirro G., Di Angelantonio, Emanuele, Falchi, Mario, Spector, Tim D., Soranzo, Nicole, Michelotti, Gregory A., Arlt, Wiebke, Lotta, Luca A., Denaxas, Spiros, Hemingway, Harry, Gamazon, Eric R., Howson, Joanna M. M., Wood, Angela M., Danesh, John, Wareham, Nicholas J., Kastenmüller, Gabi, Fauman, Eric B., Suhre, Karsten, Butterworth, Adam S., and Langenberg, Claudia

Published
2022
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4. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Abraham, James, Adkisson, Michael, Albert, Marisa, Altamirano, Luz Torres, Alvarenga, Bonny, Anderson, Matthew L., Anderson, Evan J., Arnett, Azlann, Asashima, Hiromitsu, Atkinson, Mark A., Baden, Lindsey R., Barton, Brenda, Beach, Katherine, Beagle, Elizabeth, Becker, Patrice M., Bell, Matthew R., Bernui, Mariana, Bime, Christian, Boddapati, Arun Kumar, Booth, J. Leland, Borresen, Brittney, Brakenridge, Scott C., Bristow, Laurel, Bryant, Robert, Calfee, Carolyn S., Carreño, Juan Manuel, Carrillo, Sidney, Chak, Suzanna, Chang, Iris, Connors, Jennifer, Conway, Michelle, Corry, David B., Cowan, David, Croen, Brett, Dela Cruz, Charles S., Cusimano, Gina, Eaker, Lily, Edwards, Carolyn, Ehrlich, Lauren I.R., Elashoff, David, Erickson, Heidi, Erle, David J., Farhadian, Shelli, Farrugia, Keith, Fatou, Benoit, Fernandes, Andrea, Fernandez-Sesma, Ana, Fragiadakis, Gabriela K., Furukawa, Sara, Geltman, Janelle N., Ghale, Rajani, Bermúdez González, Maria Carolina, Goonewardene, I. Michael, Guerrero, Estella Sanchez, Guirgis, Faheem W., Hafler, David A., Hamilton, Sydney, Harris, Paul, Hayati, Arash Nemati, Hendrickson, Carolyn M., Agudelo Higuita, Nelson I., Hodder, Thomas, Holland, Steven M., Hough, Catherine L., Huerta, Christopher, Hurley, Kerin C., Hutton, Scott R., Iwasaki, Akiko, Jauregui, Alejandra, Jha, Meenakshi, Johnson, Brandi, Joyner, David, Kangelaris, Kirsten N., Kelly, Geoffrey, Khalil, Zain, Khan, Zenab, Kheradmand, Farrah, Kim, James N., Kimura, Hiroki, Ko, Albert I., Kohr, Bernard, Kraft, Monica, Krummel, Matthew, Kutzler, Michele A., Lasky-Su, Jessica, Lee, Serena, Lee, Deanna, Leipold, Michael, Lentucci, Claudia, Leroux, Carolyn, Lin, Edward, Liu, Shanshan, Love, Christina, Lu, Zhengchun, Maliskova, Lenka, Manning, Brittany Roth, Manohar, Monali, Martens, Mark, McComsey, Grace A., McEnaney, Kerry, McLin, Renee, Melamed, Esther, Melnyk, Nataliya, Mendez, Kevin, Messer, William B., Metcalf, Jordan P., Michelotti, Gregory, Mick, Eran, Mohanty, Subhasis, Mosier, Jarrod, Mulder, Lubbertus C.F., Murphy, Maimouna, Nadeau, Kari R.C., Nelson, Ebony, Nelson, Allison, Nguyen, Viet, Oberhaus, Jordan, Panganiban, Bernadine, Pellegrini, Kathryn L., Pickering, Harry C., Powell, Debra L., Presnell, Scott, Pulendran, Bali, Rahman, Adeeb H., Rashid, Ahmad Sadeed, Raskin, Ariel, Reed, Elaine F., Ribeiro, Susan Pereira, Rivera, Adreanne M., Rogers, Jacob E., Rogers, Angela, Rogowski, Brandon, Rooks, Rebecca, Rosenberg-Hasson, Yael, Rothman, Jessica, Rousseau, Justin F., Salehi-Rad, Ramin, Saluvan, Mehmet, Samaha, Hady, Schaenman, Joanna, Schunk, Ron, Semenza, Nicholas C., Sen, Subha, Sevransky, Jonathan, Seyfert-Margolis, Vicki, Shaheen, Tanzia, Shaw, Albert C., Sieg, Scott, Siegel, Sarah A.R., Sigal, Natalia, Siles, Nadia, Simmons, Brent, Simon, Viviana, Singh, Gagandeep, Sinko, Lauren, Smith, Cecilia M., Smolen, Kinga K., Song, Li-Zhen, Srivastava, Komal, Sullivan, Peter, Syphurs, Caitlin, Tcheou, Johnstone, Tegos, George P., Tharp, Greg K., Tong, Alexandra, Tsitsiklis, Alexandra, Ungaro, Ricardo F., Vaysman, Tatyana, Viode, Arthur, Vita, Randi, Wang, Xiaomei, Ward, Alyssa, Ward, Dawn C., Willmore, Andrew, Woloszczuk, Kyra, Wong, Kari, Woodruff, Prescott G., Xu, Leqi, van Haren, Simon, van de Guchte, Adriana, Zhao, Yujiao, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C., Dandekar, Ravi, Qi, Jingjing, Lee, Brian H., van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P., Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E., Overton, James A., Westendorf, Kerstin, Cairns, Charles B., Rouphael, Nadine, Bosinger, Steven E., Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D., van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R., Levy, Ofer, Altman, Matthew C., Maecker, Holden, Montgomery, Ruth R., Haddad, Elias K., Sekaly, Rafick P., Esserman, Denise, Ozonoff, Al, Augustine, Alison D., Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H.

Published
2023
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5. The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery

Author

Louca, Panayiotis, Meijnikman, Abraham S., Nogal, Ana, Asnicar, Francesco, Attaye, Ilias, Vijay, Amrita, Kouraki, Afroditi, Visconti, Alessia, Wong, Kari, Berry, Sarah E., Leeming, Emily R., Mompeo, Olatz, Tettamanzi, Francesca, Baleanu, Andrei-Florin, Falchi, Mario, Hadjigeorgiou, George, Wolf, Jonathan, Acherman, Yair I.Z., Van de Laar, Arnold W., Gerdes, Victor E.A., Michelotti, Gregory A., Franks, Paul W., Segata, Nicola, Mangino, Massimo, Spector, Tim D., Bulsiewicz, William J., Nieuwdorp, Max, Valdes, Ana M., and Menni, Cristina

Published
2023
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6. Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Author

Boufaied, Nadia, primary, Chetta, Paolo, additional, Hallal, Tarek, additional, Cacciatore, Stefano, additional, Lalli, Daniela, additional, Luthold, Carole, additional, Homsy, Kevin, additional, Imada, Eddie L., additional, Syamala, Sudeepa, additional, Photopoulos, Cornelia, additional, Di Matteo, Anna, additional, de Polo, Anna, additional, Storaci, Alessandra Maria, additional, Huang, Ying, additional, Giunchi, Francesca, additional, Sheridan, Patricia A., additional, Michelotti, Gregory, additional, Nguyen, Quang-De, additional, Zhao, Xin, additional, Liu, Yang, additional, Davicioni, Elai, additional, Spratt, Daniel E., additional, Sabbioneda, Simone, additional, Maga, Giovanni, additional, Mucci, Lorelei A., additional, Ghigna, Claudia, additional, Marchionni, Luigi, additional, Butler, Lisa M., additional, Ellis, Leigh, additional, Bordeleau, François, additional, Loda, Massimo, additional, Vaira, Valentina, additional, Labbé, David P., additional, and Zadra, Giorgia, additional

Published
2024
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7. Supplementary Figure S1 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Author

Boufaied, Nadia, primary, Chetta, Paolo, primary, Hallal, Tarek, primary, Cacciatore, Stefano, primary, Lalli, Daniela, primary, Luthold, Carole, primary, Homsy, Kevin, primary, Imada, Eddie L., primary, Syamala, Sudeepa, primary, Photopoulos, Cornelia, primary, Di Matteo, Anna, primary, de Polo, Anna, primary, Storaci, Alessandra Maria, primary, Huang, Ying, primary, Giunchi, Francesca, primary, Sheridan, Patricia A., primary, Michelotti, Gregory, primary, Nguyen, Quang-De, primary, Zhao, Xin, primary, Liu, Yang, primary, Davicioni, Elai, primary, Spratt, Daniel E., primary, Sabbioneda, Simone, primary, Maga, Giovanni, primary, Mucci, Lorelei A., primary, Ghigna, Claudia, primary, Marchionni, Luigi, primary, Butler, Lisa M., primary, Ellis, Leigh, primary, Bordeleau, François, primary, Loda, Massimo, primary, Vaira, Valentina, primary, Labbé, David P., primary, and Zadra, Giorgia, primary

Published
2024
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8. Data from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Author

Boufaied, Nadia, primary, Chetta, Paolo, primary, Hallal, Tarek, primary, Cacciatore, Stefano, primary, Lalli, Daniela, primary, Luthold, Carole, primary, Homsy, Kevin, primary, Imada, Eddie L., primary, Syamala, Sudeepa, primary, Photopoulos, Cornelia, primary, Di Matteo, Anna, primary, de Polo, Anna, primary, Storaci, Alessandra Maria, primary, Huang, Ying, primary, Giunchi, Francesca, primary, Sheridan, Patricia A., primary, Michelotti, Gregory, primary, Nguyen, Quang-De, primary, Zhao, Xin, primary, Liu, Yang, primary, Davicioni, Elai, primary, Spratt, Daniel E., primary, Sabbioneda, Simone, primary, Maga, Giovanni, primary, Mucci, Lorelei A., primary, Ghigna, Claudia, primary, Marchionni, Luigi, primary, Butler, Lisa M., primary, Ellis, Leigh, primary, Bordeleau, François, primary, Loda, Massimo, primary, Vaira, Valentina, primary, Labbé, David P., primary, and Zadra, Giorgia, primary

Published
2024
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9. Supplementary Tables S1-S19 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Author

Boufaied, Nadia, primary, Chetta, Paolo, primary, Hallal, Tarek, primary, Cacciatore, Stefano, primary, Lalli, Daniela, primary, Luthold, Carole, primary, Homsy, Kevin, primary, Imada, Eddie L., primary, Syamala, Sudeepa, primary, Photopoulos, Cornelia, primary, Di Matteo, Anna, primary, de Polo, Anna, primary, Storaci, Alessandra Maria, primary, Huang, Ying, primary, Giunchi, Francesca, primary, Sheridan, Patricia A., primary, Michelotti, Gregory, primary, Nguyen, Quang-De, primary, Zhao, Xin, primary, Liu, Yang, primary, Davicioni, Elai, primary, Spratt, Daniel E., primary, Sabbioneda, Simone, primary, Maga, Giovanni, primary, Mucci, Lorelei A., primary, Ghigna, Claudia, primary, Marchionni, Luigi, primary, Butler, Lisa M., primary, Ellis, Leigh, primary, Bordeleau, François, primary, Loda, Massimo, primary, Vaira, Valentina, primary, Labbé, David P., primary, and Zadra, Giorgia, primary

Published
2024
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10. Supplementary Information from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Author

Boufaied, Nadia, primary, Chetta, Paolo, primary, Hallal, Tarek, primary, Cacciatore, Stefano, primary, Lalli, Daniela, primary, Luthold, Carole, primary, Homsy, Kevin, primary, Imada, Eddie L., primary, Syamala, Sudeepa, primary, Photopoulos, Cornelia, primary, Di Matteo, Anna, primary, de Polo, Anna, primary, Storaci, Alessandra Maria, primary, Huang, Ying, primary, Giunchi, Francesca, primary, Sheridan, Patricia A., primary, Michelotti, Gregory, primary, Nguyen, Quang-De, primary, Zhao, Xin, primary, Liu, Yang, primary, Davicioni, Elai, primary, Spratt, Daniel E., primary, Sabbioneda, Simone, primary, Maga, Giovanni, primary, Mucci, Lorelei A., primary, Ghigna, Claudia, primary, Marchionni, Luigi, primary, Butler, Lisa M., primary, Ellis, Leigh, primary, Bordeleau, François, primary, Loda, Massimo, primary, Vaira, Valentina, primary, Labbé, David P., primary, and Zadra, Giorgia, primary

Published
2024
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12. Metabolome-wide association of carotid intima media thickness identifies FDX1 as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations.

Author

Sadhu, Nilanjana, primary, Dalan, Rinkoo, additional, Jain, Pritesh R, additional, Lee, Chang Jie Mick, additional, Pakkiri, Leroy Sivappiragasam, additional, Tay, Kai Yi, additional, Mina, Theresia Handayani, additional, Low, Dorrain Yanwen, additional, Min, Yilin, additional, Ackers-Johnson, Matthew, additional, Thi, Thi Tun, additional, Kota, Vishnu Goutham, additional, Shi, Yu, additional, Liu, Yan, additional, Yu, Henry, additional, Tay, Darwin, additional, Ng, Hong Kiat, additional, Wang, Xiaoyan, additional, Wong, Kari E, additional, Lam, Max, additional, Bertin, Nicolas, additional, Wong, Eleanor Huijun, additional, Best, James Donovan, additional, Sarangarajan, Rangaprasad, additional, Elliott, Paul, additional, Riboli, Elio, additional, Lee, Jimmy, additional, Lee, Eng Sing, additional, Ngeow, Joanne, additional, Tan, Patrick, additional, Cheung, Christine, additional, Drum, Chester Lee, additional, Foo, Roger SY, additional, Michelotti, Gregory A, additional, Yu, Haojie, additional, Sheridan, Patricia A, additional, Loh, Marie, additional, and Chambers, John C, additional

Published
2024
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13. Plasma metabolites to profile pathways in noncommunicable disease multimorbidity

Author

Pietzner, Maik, Stewart, Isobel D., Raffler, Johannes, Khaw, Kay-Tee, Michelotti, Gregory A., Kastenmüller, Gabi, Wareham, Nicholas J., and Langenberg, Claudia

Subjects
Chronic diseases -- Development and progression, Comorbidity -- Development and progression, Metabolites -- Health aspects -- Physiological aspects -- Identification and classification, Biological sciences, Health
Abstract

Multimorbidity, the simultaneous presence of multiple chronic conditions, is an increasing global health problem and research into its determinants is of high priority. We used baseline untargeted plasma metabolomics profiling covering >1,000 metabolites as a comprehensive readout of human physiology to characterize pathways associated with and across 27 incident noncommunicable diseases (NCDs) assessed using electronic health record hospitalization and cancer registry data from over 11,000 participants (219,415 person years). We identified 420 metabolites shared between at least 2 NCDs, representing 65.5% of all 640 significant metabolite-disease associations. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways represented by those metabolites. Our study highlights liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity and specific health-related behaviors as antecedents of common NCD multimorbidity with potential for early prevention. We integrated results into an open-access webserver (https://omicscience.org/apps/mwasdisease/) to facilitate future research and meta-analyses. Untargeted metabolomics profiling coupled with analysis of electronic health records in over 11,000 participants in the EPIC-Norfolk cohort reveals shared pathways that contribute to multimorbidity of noncommunicable diseases., Author(s): Maik Pietzner [sup.1] , Isobel D. Stewart [sup.1] , Johannes Raffler [sup.2] , Kay-Tee Khaw [sup.3] , Gregory A. Michelotti [sup.4] , Gabi Kastenmüller [sup.1] [sup.2] , Nicholas J. [...]

Published
2021
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14. LGR5 is associated with tumor aggressiveness in papillary thyroid cancer

Author

Michelotti, Gregory, Jiang, Xiaoyin, Sosa, Julie Ann, Diehl, Anna Mae, and Henderson, Brittany Bohinc

Subjects
Rare Diseases, Cancer, Pediatric Research Initiative, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adult, Biomarkers, Tumor, Carcinoma, Carcinoma, Papillary, Cell Line, Tumor, Cell Proliferation, Female, Gene Knockdown Techniques, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Middle Aged, Mutation, Proto-Oncogene Proteins B-raf, Real-Time Polymerase Chain Reaction, Receptors, G-Protein-Coupled, Sensitivity and Specificity, Thrombospondins, Thyroid Cancer, Papillary, Thyroid Neoplasms, Wnt Signaling Pathway, beta Catenin, R-spondin, Wnt, beta-catenin, metastasis, BRAFV600E, β-catenin, Oncology and Carcinogenesis
Abstract

PurposeLeucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness.Patients and methodsUsing established human cell lines (TPC-1, KTC-1, Nthy-ori-3-1), we report LGR5 and R-spondin (RSPO1-3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients).ResultsOur results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/β-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%-72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%-97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005).ConclusionWe conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC.

Published
2015

16. A faecal metabolite signature of impaired fasting glucose: results from two independent population-based cohorts

Author

Nogal, Ana, primary, Tettamanzi, Francesca, primary, Dong, Qiuling, primary, Louca, Panayiotis, primary, Visconti, Alessia, primary, Christiansen, Colette, primary, Breuninger, Taylor, primary, Linseisen, Jakob, primary, Grallert, Harald, primary, Wawro, Nina, primary, Asnicar, Francesco, primary, Wong, Kari, primary, Baleanu, Andrei-Florin, primary, A. Michelotti, Gregory, primary, Segata, Nicola, primary, Falchi, Mario, primary, Peters, Annette, primary, W. Franks, Paul, primary, Bagnardi, Vincenzo, primary, D Spector, Tim, primary, T Bell, Jordana, primary, Gieger, Christian, primary, M Valdes, Ana, primary, and Menni, Cristina, primary

Published
2023
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17. Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation

Author

Nogal, Ana, primary, Asnicar, Francesco, additional, Vijay, Amrita, additional, Kouraki, Afroditi, additional, Visconti, Alessia, additional, Louca, Panayiotis, additional, Wong, Kari, additional, Baleanu, Andrei-Florin, additional, Giordano, Francesca, additional, Wolf, Jonathan, additional, Hadjigeorgiou, George, additional, Davies, Richard, additional, Michelotti, Gregory A., additional, Franks, Paul W., additional, Berry, Sarah E., additional, Falchi, Mario, additional, Ikram, Adeel, additional, Ollivere, Benjamin J., additional, Zheng, Amy, additional, Nightingale, Jessica, additional, Mangino, Massimo, additional, Segata, Nicola, additional, Bulsiewicz, William J., additional, Spector, Tim D., additional, Valdes, Ana M., additional, and Menni, Cristina, additional

Published
2023
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18. P07-005-23 Associations of Human Milk Metabolomics and Infant Growth in Rural Bangladesh

Author

Andrews, Chloe, primary, Monthé-Drèze, Carmen, additional, Bhushan, Brij, additional, Olson, Ingrid, additional, Perng, Wei, additional, Baye, Estifanos, additional, Baqui, Abdullah, additional, Ahmed, Salahuddin, additional, Khanam, Rasheda, additional, Rahman, Sayedur, additional, Sheridan, Patricia, additional, Michelotti, Gregory, additional, Martin, Camilia, additional, Lee, Anne, additional, and Sen, Sarbattama, additional

Published
2023
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20. Hepatic triglyceride content is intricately associated with numerous metabolites and biochemical pathways

Author

Faquih, Tariq O., primary, van Klinken, Jan Bert, additional, Li‐Gao, Ruifang, additional, Noordam, Raymond, additional, van Heemst, Diana, additional, Boone, Sebastiaan, additional, Sheridan, Patricia A., additional, Michelotti, Gregory, additional, Lamb, Hildo, additional, de Mutsert, Renée, additional, Rosendaal, Frits R., additional, van Hylckama Vlieg, Astrid, additional, van Dijk, Ko Willems, additional, and Mook‐Kanamori, Dennis O., additional

Published
2023
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21. A Fecal Metabolite Signature of Impaired Fasting Glucose: Results From Two Independent Population-Based Cohorts.

Author

Nogal, Ana, Tettamanzi, Francesca, Dong, Qiuling, Louca, Panayiotis, Visconti, Alessia, Christiansen, Colette, Breuninger, Taylor, Linseisen, Jakob, Grallert, Harald, Wawro, Nina, Asnicar, Francesco, Wong, Kari, Baleanu, Andrei-Florin, Michelotti, Gregory A., Segata, Nicola, Falchi, Mario, Peters, Annette, Franks, Paul W., Bagnardi, Vincenzo, and Spector, Tim D.

Subjects
GUT microbiome, MICROBIAL metabolites, TYPE 2 diabetes, INTESTINAL absorption, GLUCOSE
Abstract

Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02–5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16–1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97–8], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset. Article Highlights: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Data from Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes

Author

Markowitz, Geoffrey J., primary, Yang, Pengyuan, primary, Fu, Jing, primary, Michelotti, Gregory A., primary, Chen, Rui, primary, Sui, Jianhua, primary, Yang, Bin, primary, Qin, Wen-Hao, primary, Zhang, Zheng, primary, Wang, Fu-Sheng, primary, Diehl, Anna Mae, primary, Li, Qi-Jing, primary, Wang, Hongyang, primary, and Wang, Xiao-Fan, primary

Published
2023
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23. Supplementary Materials and Methods from Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes

Author

Markowitz, Geoffrey J., primary, Yang, Pengyuan, primary, Fu, Jing, primary, Michelotti, Gregory A., primary, Chen, Rui, primary, Sui, Jianhua, primary, Yang, Bin, primary, Qin, Wen-Hao, primary, Zhang, Zheng, primary, Wang, Fu-Sheng, primary, Diehl, Anna Mae, primary, Li, Qi-Jing, primary, Wang, Hongyang, primary, and Wang, Xiao-Fan, primary

Published
2023
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24. Supplementary Figure Legends from Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes

Author

Markowitz, Geoffrey J., primary, Yang, Pengyuan, primary, Fu, Jing, primary, Michelotti, Gregory A., primary, Chen, Rui, primary, Sui, Jianhua, primary, Yang, Bin, primary, Qin, Wen-Hao, primary, Zhang, Zheng, primary, Wang, Fu-Sheng, primary, Diehl, Anna Mae, primary, Li, Qi-Jing, primary, Wang, Hongyang, primary, and Wang, Xiao-Fan, primary

Published
2023
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25. Supplemental Figure S17 from Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes

Author

Markowitz, Geoffrey J., primary, Yang, Pengyuan, primary, Fu, Jing, primary, Michelotti, Gregory A., primary, Chen, Rui, primary, Sui, Jianhua, primary, Yang, Bin, primary, Qin, Wen-Hao, primary, Zhang, Zheng, primary, Wang, Fu-Sheng, primary, Diehl, Anna Mae, primary, Li, Qi-Jing, primary, Wang, Hongyang, primary, and Wang, Xiao-Fan, primary

Published
2023
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26. Supplementary Figures and Tables from Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes

Author

Markowitz, Geoffrey J., primary, Yang, Pengyuan, primary, Fu, Jing, primary, Michelotti, Gregory A., primary, Chen, Rui, primary, Sui, Jianhua, primary, Yang, Bin, primary, Qin, Wen-Hao, primary, Zhang, Zheng, primary, Wang, Fu-Sheng, primary, Diehl, Anna Mae, primary, Li, Qi-Jing, primary, Wang, Hongyang, primary, and Wang, Xiao-Fan, primary

Published
2023
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27. Data from Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma

Author

Chan, Isaac S., primary, Guy, Cynthia D., primary, Chen, Yuping, primary, Lu, Jiuyi, primary, Swiderska-Syn, Marzena, primary, Michelotti, Gregory A., primary, Karaca, Gamze, primary, Xie, Guanhua, primary, Krüger, Leandi, primary, Syn, Wing-Kin, primary, Anderson, Blair R., primary, Pereira, Thiago A., primary, Choi, Steve S., primary, Baldwin, Albert S., primary, and Diehl, Anna Mae, primary

Published
2023
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28. Supplementary Methods , Figure Legends 1-5 from Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma

Author

Chan, Isaac S., primary, Guy, Cynthia D., primary, Chen, Yuping, primary, Lu, Jiuyi, primary, Swiderska-Syn, Marzena, primary, Michelotti, Gregory A., primary, Karaca, Gamze, primary, Xie, Guanhua, primary, Krüger, Leandi, primary, Syn, Wing-Kin, primary, Anderson, Blair R., primary, Pereira, Thiago A., primary, Choi, Steve S., primary, Baldwin, Albert S., primary, and Diehl, Anna Mae, primary

Published
2023
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29. Supplementary Figures 1-5 from Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma

Author

Chan, Isaac S., primary, Guy, Cynthia D., primary, Chen, Yuping, primary, Lu, Jiuyi, primary, Swiderska-Syn, Marzena, primary, Michelotti, Gregory A., primary, Karaca, Gamze, primary, Xie, Guanhua, primary, Krüger, Leandi, primary, Syn, Wing-Kin, primary, Anderson, Blair R., primary, Pereira, Thiago A., primary, Choi, Steve S., primary, Baldwin, Albert S., primary, and Diehl, Anna Mae, primary

Published
2023
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30. Untargeted metabolomics profiling in pediatric patients and adult populations indicates a connection between lipid imbalance and epilepsy

Author

Oja, Kaisa Teele, primary, Ilisson, Mihkel, additional, Reinson, Karit, additional, Muru, Kai, additional, Reimand, Tiia, additional, Peterson, Hedi, additional, Fishman, Dmytro, additional, Esko, Tõnu, additional, Haller, Toomas, additional, Kronberg, Jaanika, additional, Wojcik, Monica H., additional, Kennedy, Adam, additional, Michelotti, Gregory, additional, O’Donnell-Luria, Anne, additional, Õiglane-Šlik, Eve, additional, Pajusalu, Sander, additional, and Õunap, Katrin, additional

Published
2023
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31. Supplementary Table 1 from Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma

Author

Chan, Isaac S., primary, Guy, Cynthia D., primary, Chen, Yuping, primary, Lu, Jiuyi, primary, Swiderska-Syn, Marzena, primary, Michelotti, Gregory A., primary, Karaca, Gamze, primary, Xie, Guanhua, primary, Krüger, Leandi, primary, Syn, Wing-Kin, primary, Anderson, Blair R., primary, Pereira, Thiago A., primary, Choi, Steve S., primary, Baldwin, Albert S., primary, and Diehl, Anna Mae, primary

Published
2023
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39. Metabolomic Scores Mediate Associations between Dietary Patterns and Insulin Homeostasis in The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Author

Wood, Alexis, primary, Senn, MacKenzie, additional, Jensen, Elizabeth, additional, Bertoni, Alain, additional, Wong, Kari, additional, Sheridan, Patricia, additional, Michelotti, Gregory, additional, Crago, Osa, additional, Rotter, Jerome, additional, Chen, Yii-Der, additional, and Goodarzi, Mark, additional

Published
2022
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45. Cross-platform genetic discovery of small molecule products of metabolism and application to clinical outcomes

Author

Lotta, Luca A., Pietzner, Maik, Stewart, Isobel D., Wittemans, Laura B.L., Li, Chen, Bonelli, Roberto, Raffler, Johannes, Biggs, Emma K., Oliver-Williams, Clare, Auyeung, Victoria P.W., Luan, Jian’an, Wheeler, Eleanor, Paige, Ellie, Surendran, Praveen, Michelotti, Gregory A., Scott, Robert A., Burgess, Stephen, Zuber, Verena, Sanderson, Eleanor, Koulman, Albert, Imamura, Fumiaki, Forouhi, Nita G., Khaw, Kay-Tee, Griffin, Julian L., Wood, Angela M., Kastenmüller, Gabi, Danesh, John, Butterworth, Adam S., Gribble, Fiona M., Reimann, Frank, Bahlo, Melanie, Fauman, Eric, Wareham, Nicholas J., and Langenberg, Claudia

Subjects
Eye Diseases, Genome, Human, Glycine, Mutation, Missense, Genetic Pleiotropy, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Article, Metabolism, Phenotype, Diabetes Mellitus, Type 2, Gene Frequency, Genetic Loci, Health, Sample Size, Glucagon-Like Peptide-2 Receptor, Linear Models, Metabolome, Serine, Humans, Retinal Telangiectasis, Metabolism, Inborn Errors
Abstract

Circulating levels of small molecules or metabolites are highly heritable, but the impact of genetic differences in metabolism on human health is not well understood. In this cross-platform, genome-wide meta-analysis of 174 metabolite levels across six cohorts including up to 86,507 participants (70% unpublished data), we identify 499 (362 novel) genome-wide significant associations (p

Published
2021

46. A cross-platform approach identifies genetic regulators of human metabolism and health

Author

Lotta, Luca A, Pietzner, Maik, Stewart, Isobel D, Wittemans, Laura BL, Li, Chen, Bonelli, Roberto, Raffler, Johannes, Biggs, Emma K, Oliver-Williams, Clare, Auyeung, Victoria PW, Luan, Jian'an, Wheeler, Eleanor, Paige, Ellie, Surendran, Praveen, Michelotti, Gregory A, Scott, Robert A, Burgess, Stephen, Zuber, Verena, Sanderson, Eleanor, Koulman, Albert, Imamura, Fumiaki, Forouhi, Nita G, Khaw, Kay-Tee, MacTel Consortium, Griffin, Julian L, Wood, Angela M, Kastenmüller, Gabi, Danesh, John, Butterworth, Adam S, Gribble, Fiona M, Reimann, Frank, Bahlo, Melanie, Fauman, Eric, Wareham, Nicholas J, Langenberg, Claudia, Pietzner, Maik [0000-0003-3437-9963], Au Yeung, Victoria [0000-0002-0823-3963], Luan, Jian'an [0000-0003-3137-6337], Wheeler, Eleanor [0000-0002-8616-6444], Burgess, Stephen [0000-0001-5365-8760], Koulman, Albert [0000-0001-9998-051X], Imamura, Fumiaki [0000-0002-6841-8396], Forouhi, Nita [0000-0002-5041-248X], Wood, Angela [0000-0002-7937-304X], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository

Subjects
Eye Diseases, Genome, Human, Glycine, Mutation, Missense, Genetic Pleiotropy, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Metabolism, Phenotype, Diabetes Mellitus, Type 2, Gene Frequency, Genetic Loci, Health, Sample Size, Glucagon-Like Peptide-2 Receptor, Linear Models, Metabolome, Serine, Humans, Retinal Telangiectasis, Metabolism, Inborn Errors
Abstract

In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10-10) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.

Published
2021

47. Smoothened is a master regulator of adult liver repair

Author

Michelotti, Gregory A., Xie, Guanhua, Swiderska, Marzena, Choi, Steve S., Karaca, Gamze, Kruger, Leandi, Premont, Richard, Yang, Liu, Syn, Wing-Kin, Metzger, Daniel, and Diehl, Anna Mae

Subjects
Liver -- Transplantation, Liver diseases -- Diagnosis -- Care and treatment -- Research, Health care industry
Abstract

When regenerative processes cannot keep pace with cell death, functional epithelia are replaced by scar. Scarring is characterized by both excessive accumulation of fibrous matrix and persistent outgrowth of cell [...]

Published
2013
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