Diet, genetics, and the gut microbiome drive dynamic changes in plasma metabolites
Open accessAbstract
Diet, genetics, and the gut microbiome are determinants of metabolic status, in part through production of metabolites by the gut microbiota. To understand the mechanisms linking these factors, we performed LC-MS-based metabolomic analysis of cecal contents and plasma from C57BL/6J, 129S1/SvImJ, and 129S6/SvEvTac mice on chow or a high-fat diet (HFD) and HFD-treated with vancomycin or metronidazole. Prediction of the functional metagenome of gut bacteria by PICRUSt analysis of 16S sequences revealed dramatic differences in microbial metabolism. Cecal and plasma metabolites showed multifold differences reflecting the combined and integrated effects of diet, antibiotics, host background, and the gut microbiome. Eighteen plasma metabolites correlated positively or negatively with host insulin resistance across strains and diets. Over 1,000 still-unidentified metabolite peaks were also highly regulated by diet, antibiotics, and genetic background. Thus, diet, host genetics, and the gut microbiota interact to create distinct responses in plasma metabolites, which can contribute to regulation of metabolism and insulin resistance.
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An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · cited 1× · see citing works
“These changes in the microbiota have been linked to development of obesity, diabetes, and metabolic syndrome, and many of these phenotypes can be transferred, at least in part, via the microbiome to germ-free mice (Ridaura et al., 2013; Turnbaugh et al., 2006).”
BackgroundFrom Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites
Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F. (2016) · Cell · doi:10.1016/j.cell.2016.05.041 · Cited by 7,070 · cited 2× · see citing works
“metabolites (Koh et al., 2016), but propionate levels were unchanged in the cecum of any strain by HFD alone, but the HFD increased propionate in the plasma of B6J mice.”
BackgroundGut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597 · cited 3× · see citing works
“…the plasma levels of trimethylamine-N-oxide, another bacterial metabolite that has been linked to cardiovascular disease risk (Tang et al., 2013; Wang et al., 2011b), were markedly decreased by vancomycin, but not metronidazole, in B6J and 129J mice, whereas cecal levels showed no consistent…”
BackgroundCommensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · cited 1× · see citing works
“It is known that mice receiving short-term antibiotics or germfree mice show enlargement of the cecum (Furusawa et al., 2013; Savage and Dubos, 1968).”
BackgroundRichness of human gut microbiome correlates with metabolic markers
Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-M., Kennedy, S., et al. (2013) · Nature · doi:10.1038/nature12506 · Cited by 4,662 · cited 1× · see citing works
“INTRODUCTION Over the past decade, it has become clear that one factor affecting systemic metabolism is the composition of the gut microbiota (Le Chatelier et al., 2013; Lynch and Pedersen, 2016; Schroeder and Bäckhed, 2016).”
BackgroundGut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., et al. (2013) · Science · doi:10.1126/science.1241214 · Cited by 3,788 · cited 1× · see citing works
“These changes in the microbiota have been linked to development of obesity, diabetes, and metabolic syndrome, and many of these phenotypes can be transferred, at least in part, via the microbiome to germ-free mice (Ridaura et al., 2013; Turnbaugh et al., 2006).”
The Human Intestinal Microbiome in Health and Disease
Lynch, S. V., & Pedersen, O. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1600266 · Cited by 3,637 · cited 2× · see citing works
“Over the past decade, it has become clear that one factor affecting systemic metabolism is the composition of the gut microbiota (Le Chatelier et al., 2013; Lynch and Pedersen, 2016; Schroeder and Bäckhed, 2016).”
BackgroundIntestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,402 · cited 3× · see citing works
“In contrast, the plasma levels of trimethylamine-N-oxide, another bacterial metabolite that has been linked to cardiovascular disease risk (Tang et al., 2013; Wang et al., 2011b), were markedly decreased by vancomycin, but not metronidazole, in B6J and 129J mice, whereas cecal levels showed no consistent pattern (Figu…”
BackgroundNewgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.002 · Cited by 3,165 · cited 1× · see citing works
“As reported previously (Newgard et al., 2009), branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine were elevated in the plasma by an HFD.”
BackgroundMetabolite profiles and the risk of developing diabetes
Wang, T. J., Larson, M. G., Vasan, R. S., Cheng, S., Rhee, E. P., McCabe, E., Lewis, G. D., Fox, C. S., Jacques, P. F., Fernandez, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2307 · Cited by 3,143 · cited 3× · see citing works
“…the plasma levels of trimethylamine-N-oxide, another bacterial metabolite that has been linked to cardiovascular disease risk (Tang et al., 2013; Wang et al., 2011b), were markedly decreased by vancomycin, but not metronidazole, in B6J and 129J mice, whereas cecal levels showed no consistent…”
BackgroundMetabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812874106 · Cited by 2,677 · cited 3× · see citing works
“components to produce energy and metabolites, many of which are taken up into the blood stream where they can be further metabolized or affect host metabolism (Pedersen et al., 2016; Wikoff et al., 2009).”
BackgroundTolhurst, G., Heffron, H., Lam, Y. S., Parker, H. E., Habib, A. M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., & Gribble, F. M. (2012) · Diabetes · doi:10.2337/db11-1019 · Cited by 2,404 · cited 1× · see citing works
“For example, short-chain fatty acids (SCFAs), derived from otherwise undigestible fiber, have generally beneficial effects on the host, including anti-obesity and anti-diabetic actions (Chang et al., 2014; Kimura et al., 2013; Tolhurst et al., 2012).”
BackgroundShort-chain fatty acids in control of body weight and insulin sensitivity
Canfora, E. E., Jocken, J. W., & Blaak, E. E. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.128 · Cited by 2,298 · cited 2× · see citing works
“…butyrate, and propionate not only serve as important energy sources for the intestinal epithelium and the liver but can also can modify insulin secretion, immune system function, appetite, and adipose function (Bouter et al., 2017; Canfora et al., 2015; Holmes et al., 2012; Perry et al., 2016).”
BackgroundMETLIN—a metabolite mass spectral database
Smith, C. A., Maille, G. O., Want, E. J., Qin, C., Trauger, S. A., Brandon, T. R., Custodio, D. E., Abagyan, R., & Siuzdak, G. (2005) · Therapeutic Drug Monitoring · doi:10.1097/01.ftd.0000179845.53213.39 · Cited by 2,226 · cited 2× · see citing works
“edu) (Smith et al., 2005) and reference standards, we have begun to identify a few of these.”
BackgroundMethodObesity-induced gut microbial metabolite promotes liver cancer through senescence secretome
Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. (2013) · Nature · doi:10.1038/nature12347 · Cited by 2,219 · cited 1× · see citing works
“Deoxycholic acid, a secondary bile acid produced by the gut microbiota, promotes development of hepatocellular carcinoma (Yoshimoto et al., 2013).”
BackgroundMicrobiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., & Mithieux, G. (2014) · Cell · doi:10.1016/j.cell.2013.12.016 · Cited by 2,200 · cited 1× · see citing works
“On the other hand, propionate, which has been reported to have a favorable effect on insulin resistance (De Vadder et al., 2014), is also decreased in antibiotic-treated mice despite their improved insulin sensitivity.”
BackgroundChang, P. V., Hao, L., Offermanns, S., & Medzhitov, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322269111 · Cited by 2,175 · cited 1× · see citing works
“For example, short-chain fatty acids (SCFAs), derived from otherwise undigestible fiber, have generally beneficial effects on the host, including anti-obesity and anti-diabetic actions (Chang et al., 2014; Kimura et al., 2013; Tolhurst et al., 2012).”
BackgroundHuman gut microbes impact host serum metabolome and insulin sensitivity
Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A. H., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., et al. (2016) · Nature · doi:10.1038/nature18646 · Cited by 2,116 · cited 1× · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript components to produce energy and metabolites, many of which are taken up into the blood stream where they can be further metabolized or affect host metabolism (Pedersen et al., 2016; Wikoff et al., 2009).”
BackgroundTGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.001 · Cited by 1,885 · cited 2× · see citing works
“For example, primary bile acids are converted to secondary bile acids by gut microbiotas, and these secondary bile acids not only aid in fat absorption, but they also are reabsorbed into the circulation, where they serve as ligands for the bile acid receptors farnesoid X (FXR) and TGR5 on host cells, leading to effect…”
BackgroundAntibiotics in early life alter the murine colonic microbiome and adiposity
Cho, I., Yamanishi, S., Cox, L., Methé, B. A., Zavadil, J., Li, K., Gao, Z., Mahana, D., Raju, K., Teitler, I., et al. (2012) · Nature · doi:10.1038/nature11400 · Cited by 1,613 · cited 1× · see citing works
“The nature of the microbial community and its changes in response to environmental factors such as dietary nutrients, fiber, and antibiotics is dependent on the genetic background of the host (Cho et al., 2012; Fujisaka et al., 2016; Parks et al., 2015; Tamburini et al., 2016; Ussar et al., 2016).”
BackgroundKimura, I., Ozawa, K., Inoue, D., Imamura, T., Kimura, K., Maeda, T., Terasawa, K., Kashihara, D., Hirano, K., Tani, T., et al. (2013) · Nature Communications · doi:10.1038/ncomms2852 · Cited by 1,512 · cited 1× · see citing works
“For example, short-chain fatty acids (SCFAs), derived from otherwise undigestible fiber, have generally beneficial effects on the host, including anti-obesity and anti-diabetic actions (Chang et al., 2014; Kimura et al., 2013; Tolhurst et al., 2012).”
BackgroundSignals from the gut microbiota to distant organs in physiology and disease
Schroeder, B. O., & Bäckhed, F. (2016) · Nature Medicine · doi:10.1038/nm.4185 · Cited by 1,409 · cited 4× · see citing works
“Over the past decade, it has become clear that one factor affecting systemic metabolism is the composition of the gut microbiota (Le Chatelier et al., 2013; Lynch and Pedersen, 2016; Schroeder and Bäckhed, 2016).”
BackgroundInfluentialAcetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome
Perry, R. J., Peng, L., Barry, N. A., Cline, G. W., Zhang, D., Cardone, R. L., Petersen, K. F., Kibbey, R. G., Goodman, A. L., & Shulman, G. I. (2016) · Nature · doi:10.1038/nature18309 · Cited by 1,299 · cited 2× · see citing works
“…butyrate, and propionate not only serve as important energy sources for the intestinal epithelium and the liver but can also can modify insulin secretion, immune system function, appetite, and adipose function (Bouter et al., 2017; Canfora et al., 2015; Holmes et al., 2012; Perry et al., 2016).”
BackgroundThe microbiome in early life: Implications for health outcomes
Tamburini, S., Shen, N., Wu, H. C., & Clemente, J. C. (2016) · Nature Medicine · doi:10.1038/nm.4142 · Cited by 1,213 · cited 2× · see citing works
“Although the composition is influenced by both host genetics and environmental factors, the gut microbiome can be re-modeled throughout life, depending on many factors, including diet, antibiotics, and gastrointestinal disease (Schroeder and Bäckhed, 2016; Tamburini et al., 2016).”
BackgroundGadaleta, R. M., van Erpecum, K. J., Oldenburg, B., Willemsen, E. C. L., Renooij, W., Murzilli, S., Klomp, L. W. J., Siersema, P. D., Schipper, M. E. I., Danese, S., et al. (2011) · Gut · doi:10.1136/gut.2010.212159 · Cited by 870 · cited 2× · see citing works
“For example, primary bile acids are converted to secondary bile acids by gut microbiotas, and these secondary bile acids not only aid in fat absorption, but they also are reabsorbed into the circulation, where they serve as ligands for the bile acid receptors farnesoid X (FXR) and TGR5 on host cells, leading to effect…”
BackgroundGall, W. E., Beebe, K. D., Lawton, K. A., Adam, K., Mitchell, M. W., Nakhle, P. J., Ryals, J. A., Milburn, M. V., Nannipieri, M., Camastra, S., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010883 · Cited by 702 · cited 3× · see citing works
“Importantly, 2-aminoadipoate, alpha-hydroxybutyrate, and N-acetylglycine have also been previously identified in humans as potential biomarkers for diabetes risk and insulin resistance (Gall et al., 2010; Menni et al., 2013; Wang et al., 2013), as have patterns of lipids with lower fatty acyl carbon number and double…”
BackgroundIntestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease
Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W., Cai, J., Qi, Y., Fang, Z.-Z., Takahashi, S., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76738 · Cited by 693 · cited 2× · see citing works
“For example, primary bile acids are converted to secondary bile acids by gut microbiotas, and these secondary bile acids not only aid in fat absorption, but they also are reabsorbed into the circulation, where they serve as ligands for the bile acid receptors farnesoid X (FXR) and TGR5 on host cells, leading to effect…”
BackgroundRhee, E. P., Cheng, S., Larson, M. G., Walford, G. A., Lewis, G. D., McCabe, E., Yang, E., Farrell, L., Fox, C. S., O’Donnell, C. J., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44442 · Cited by 647 · cited 2× · see citing works
“…and N-acetylglycine have also been previously identified in humans as potential biomarkers for diabetes risk and insulin resistance (Gall et al., 2010; Menni et al., 2013; Wang et al., 2013), as have patterns of lipids with lower fatty acyl carbon number and double bond content (Rhee et al., 2011).”
BackgroundSelf-citationUssar, S., Griffin, N. W., Bézy, O., Fujisaka, S., Vienberg, S. G., Softic, S., Deng, L., Bry, L., Gordon, J. I., & Kahn, C. R. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.007 · Cited by 529 · cited 4× · see citing works
“However, some of the difference between strains is due to differences in their gut microbiotas (Ussar et al., 2015).”
BackgroundResultInfluentialZhang, L., & Davies, S. S. (2016) · Genome Medicine · doi:10.1186/s13073-016-0296-x · Cited by 499 · cited 1× · see citing works
“Lachnospiraceae have also been shown to affect short- and long-chain fatty acid synthesis (Zhang and Davies, 2016).”
BackgroundGut microbiota composition and activity in relation to host metabolic phenotype and disease risk
Holmes, E., Li, J. V., Marchesi, J. R., & Nicholson, J. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.007 · Cited by 490 · cited 2× · see citing works
“…butyrate, and propionate not only serve as important energy sources for the intestinal epithelium and the liver but can also can modify insulin secretion, immune system function, appetite, and adipose function (Bouter et al., 2017; Canfora et al., 2015; Holmes et al., 2012; Perry et al., 2016).”
BackgroundErtunc, M. E., & Hotamışlıgil, G. S. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r066514 · Cited by 485 · see citing works
2-Aminoadipic acid is a biomarker for diabetes risk
Wang, T. J., Ngo, D., Psychogios, N., Dejam, A., Larson, M. G., Vasan, R. S., Ghorbani, A., O’Sullivan, J., Cheng, S. C., Rhee, E. P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64801 · Cited by 450 · cited 3× · see citing works
“…and N-acetylglycine have also been previously identified in humans as potential biomarkers for diabetes risk and insulin resistance (Gall et al., 2010; Menni et al., 2013; Wang et al., 2013), as have patterns of lipids with lower fatty acyl carbon number and double bond content (Rhee et al., 2011).”
BackgroundRole of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction
Bouter, K. E. C., van Raalte, D. H., Groen, A. K., & Nieuwdorp, M. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.12.048 · Cited by 433 · see citing works
Role of the Microbiome in Energy Regulation and Metabolism
Nieuwdorp, M., Gilijamse, P. W., Pai, N., & Kaplan, L. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.008 · Cited by 421 · cited 1× · see citing works
“There are many classes of bacterial metabolites in addition to bile acids that can be modified by factors such as diet and antibiotic treatment (Brown and Hazen, 2017; Nieuwdorp et al., 2014).”
BackgroundMenni, C., Fauman, E., Erte, I., Perry, J. R. B., Kastenmüller, G., Shin, S.-Y., Petersen, A.-K., Hyde, C., Psatha, M., Ward, K. J., et al. (2013) · Diabetes · doi:10.2337/db13-0570 · Cited by 416 · cited 3× · see citing works
“…and N-acetylglycine have also been previously identified in humans as potential biomarkers for diabetes risk and insulin resistance (Gall et al., 2010; Menni et al., 2013; Wang et al., 2013), as have patterns of lipids with lower fatty acyl carbon number and double bond content (Rhee et al., 2011).”
BackgroundKameyama, K., & Itoh, K. (2014) · Microbes and Environments · doi:10.1264/jsme2.me14054 · Cited by 379 · cited 1× · see citing works
“Lachnospiraceae have been identified as over-represented in the gut microbiome of obese mice, and colonization of germ-free obese mice with Lachnospiraceae induces hyperglycemia (Kameyama and Itoh, 2014).”
BackgroundJakobsdottir, G., Xu, J., Molin, G., Ahrné, S., & NYMAN, M. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080476 · Cited by 297 · cited 2× · see citing works
“It has been previously shown that cecum size is increased in germ-free mice (Jakobsdottir et al., 2013).”
BackgroundGenetic Determinants of Energy Expenditure and Insulin Resistance in Diet-Induced Obesity in Mice
Almind, K., & Kahn, C. R. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3274 · Cited by 256 · cited 1× · see citing works
“C57BL/6J (B6J) mice from Jackson Laboratories (Jax) are obesity- and diabetes-prone, whereas 129S1/SvImJ (129J) mice from the same vendor are obesity- and diabetes-resistant (Almind and Kahn, 2004).”
BackgroundGenetic Architecture of Insulin Resistance in the Mouse
Parks, B. W., Sallam, T., Mehrabian, M., Psychogios, N., Hui, S. T., Norheim, F., Castellani, L. W., Rau, C. D., Pan, C., Phun, J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.01.002 · Cited by 249 · cited 2× · see citing works
“We and others have previously shown that different strains of mice and mice from different vendors exhibit different rates of obesity and diabetes when challenged with a high-fat diet (Parks et al., 2015; Ussar et al., 2016).”
BackgroundDiabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels
Dambrova, M., Latkovskis, G., Kuka, J., Strele, I., Konrade, I., Grinberga, S., Hartmane, D., Pugovics, O., Erglis, A., & Liepinsh, E. (2016) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0035-1569330 · Cited by 229 · cited 1× · see citing works
“Another bacterial metabolite reported to have a negative effect on glucose metabolism (Dambrova et al., 2016) that is decreased by antibiotics in the plasma is TMAO, and this occurs with little effect on the cecal levels of the metabolite.”
BackgroundRecurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles
Allegretti, J. R., Kearney, S. M., Li, N., Bogart, E., Bullock, K. H., Gerber, G. K., Bry, L., Clish, C. B., Alm, E. J., & Korzenik, J. R. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13616 · Cited by 193 · cited 2× · see citing works
“…Functional Pathways in the Microbiome To understand the potential implications of the different bacterial communities, we performed PICRUSt analysis, a computational approach that predicts the functional composition of the bacterial metagenome using 16S rRNA data (Allegretti et al., 2016).”
MethodKuda, O., Březinová, M., Rombaldová, M., Slavı́ková, B., Pošta, M., Beier, P., Janovská, P., Veleba, J., Kopecký, J., Kudová, E., et al. (2016) · Diabetes · doi:10.2337/db16-0385 · Cited by 184 · cited 1× · see citing works
“Overall, the changes in plasma fatty acid levels on an HFD reflected an increase in proinflammatory fatty acids, such as adrenic and stearic acid, and a decrease in anti-inflammatory fatty acids, such as eicosopentaenoic and docosohexanoic acids (Kuda et al., 2016; Yamada et al., 2017).”
BackgroundAntibiotic effects on gut microbiota and metabolism are host dependent
Fujisaka, S., Ussar, S., Clish, C. B., Devkota, S., Dreyfuss, J. M., Sakaguchi, M., Soto, M., Konishi, M., Softic, S., Altındiş, E., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86674 · Cited by 166 · cited 15× · see citing works
“For example, primary bile acids are converted to secondary bile acids by gut microbiotas, and these secondary bile acids not only aid in fat absorption, but they also are reabsorbed into the circulation, where they serve as ligands for the bile acid receptors farnesoid X (FXR) and TGR5 on host cells, leading to effect…”
BackgroundResultInfluentialInteractions between host genetics and gut microbiome in diabetes and metabolic syndrome
Ussar, S., Fujisaka, S., & Kahn, C. R. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.004 · Cited by 157 · cited 2× · see citing works
“We and others have previously shown that different strains of mice and mice from different vendors exhibit different rates of obesity and diabetes when challenged with a high-fat diet (Parks et al., 2015; Ussar et al., 2016).”
BackgroundReview of the association between meat consumption and risk of colorectal cancer
Kim, E., Coelho, D., & Blachier, F. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.07.018 · Cited by 155 · cited 1× · see citing works
“On the other hand, N-nitroso compounds, ammonia, and hydrogen sulfide derived by bacteria from dietary protein can induce reactive oxygen species (ROS) and DNA damage and activate inflammatory pathways (Kim et al., 2013).”
BackgroundALTERATIONS IN THE MOUSE CECUM AND ITS FLORA PRODUCED BY ANTIBACTERIAL DRUGS
Savage, D. C., & Dubos, R. J. (1968) · The Journal of Experimental Medicine · doi:10.1084/jem.128.1.97 · Cited by 133 · cited 1× · see citing works
“It is known that mice receiving short-term antibiotics or germfree mice show enlargement of the cecum (Furusawa et al., 2013; Savage and Dubos, 1968).”
BackgroundTryptophan Predicts the Risk for Future Type 2 Diabetes
Chen, T., Zheng, X., Ma, X., Bao, Y., Ni, Y., Hu, C., Rajani, C., Huang, F., Zhao, A., Jia, W., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162192 · Cited by 113 · cited 1× · see citing works
“Aromatic amino acids have been linked to insulin resistance (Chen et al., 2016; Wang et al., 2011a) and showed multiple pathway-specific changes (Figure 5B).”
BackgroundBrown, J. M., & Hazen, S. L. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.765388 · Cited by 108 · cited 1× · see citing works
“There are many classes of bacterial metabolites in addition to bile acids that can be modified by factors such as diet and antibiotic treatment (Brown and Hazen, 2017; Nieuwdorp et al., 2014).”
BackgroundEffect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism
Mikkelsen, S. U., Frost, M., Bahl, M. I., Licht, T. R., Jensen, U. S., Rosenberg, J., Pedersen, O. B., Hansen, T. F., Rehfeld, J. F., Holst, J. J., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142352 · Cited by 104 · cited 1× · see citing works
“It is not surprising, therefore, that changes in the communities of organisms in the intestine can contribute to the pathogenesis of metabolic diseases, including obesity, type 2 diabetes, and the metabolic syndrome (Mikkelsen et al., 2015; Schroeder and Bäckhed, 2016).”
BackgroundYamada, H., Umemoto, T., Kakei, M., Momomura, S., Kawakami, M., Ishikawa, S., & Hara, K. (2017) · Nutrition & Metabolism · doi:10.1186/s12986-017-0188-0 · Cited by 60 · cited 1× · see citing works
“Overall, the changes in plasma fatty acid levels on an HFD reflected an increase in proinflammatory fatty acids, such as adrenic and stearic acid, and a decrease in anti-inflammatory fatty acids, such as eicosopentaenoic and docosohexanoic acids (Kuda et al., 2016; Yamada et al., 2017).”
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Gut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398 · see citing works
GABA-modulating bacteria of the human gut microbiota
Strandwitz, P., Kim, K. H., Terekhova, D., Liu, J. K., Sharma, A., Levering, J., McDonald, D., Dietrich, D., Ramadhar, T. R., Lekbua, A., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0307-3 · Cited by 1,170 · see citing works
Chen, Y., Xu, J., & Chen, Y. (2021) · Nutrients · doi:10.3390/nu13062099 · Cited by 917 · see citing works
“Similarly, antibiotic administration, which leads to the acquired deprivation of gut bacteria, also alters the levels of neurotransmitters and their precursors in the gut and blood [25,72].”
BackgroundScheiman, J., Luber, J. M., Chavkin, T. A., MacDonald, T., Tung, A., Pham, L.-D., Wibowo, M. C., Wurth, R. C., Punthambaker, S., Tierney, B. T., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0485-4 · Cited by 892 · see citing works
The maternal microbiome modulates fetal neurodevelopment in mice
Vuong, H. E., Pronovost, G. N., Williams, D. W., Coley, E. J. L., Siegler, E. L., Qiu, A., Kazantsev, M., Wilson, C. J., Rendon, T., & Hsiao, E. Y. (2020) · Nature · doi:10.1038/s41586-020-2745-3 · Cited by 564 · see citing works
Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice
Kimura, I., Miyamoto, J., Ohue‐Kitano, R., Watanabe, K., Yamada, T., Onuki, M., Aoki, R., Isobe, Y., Kashihara, D., Inoue, D., et al. (2020) · Science · doi:10.1126/science.aaw8429 · Cited by 488 · see citing works
“Such variation may be attributed to gut microbial composition, which is substantially affected by host genetic backgrounds (20, 22).”
BackgroundSignalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators
Han, H., Yi, B., Zhong, R., Wang, M., Zhang, S., Ma, J., Yin, Y., Yin, J., Chen, L., & Zhang, H. (2021) · Microbiome · doi:10.1186/s40168-021-01093-y · Cited by 292 · see citing works
The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View
Xavier, J. B., Young, V. B., Skufca, J. D., Ginty, F., Testerman, T. L., Pearson, A. T., Macklin, P., Mitchell, A., Shmulevich, I., Xie, L., et al. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.01.004 · Cited by 268 · see citing works
“The host can absorb or reabsorb some of those microbially converted metabolites which then enter the circulation [7], and from circulation the microbial products can reach distant tissues and impact on cancer progression there.”
BackgroundSang, T., Guo, C., Guo, D., Wu, J., Wang, Y., Wang, Y., Chen, J., Chen, C., Wu, K., Na, K., et al. (2021) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2020.117594 · Cited by 268 · see citing works
Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier
Usuda, H., Okamoto, T., & Wada, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147613 · Cited by 258 · see citing works
Microbiota Metabolites in Health and Disease
McCarville, J. L., Chen, G. Y., Cuevas, V. D., Troha, K., & Ayres, J. S. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-071219-125715 · Cited by 251 · see citing works
Gamma-aminobutyric acid as a potential postbiotic mediator in the gut–brain axis
Braga, J. D., Thongngam, M., & Kumrungsee, T. (2024) · npj Science of Food · doi:10.1038/s41538-024-00253-2 · Cited by 229 · see citing works
“Studies 40,85,86 .”
BackgroundObesity, diabetes, and the gut microbiome: an updated review
Singer-Englar, T., Barlow, G. M., & Mathur, R. (2018) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2019.1543023 · Cited by 215 · see citing works
“which were strongly influenced by diet, antibiotics, and genetic background, but which are as yet unidentified [156].”
BackgroundGut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism
Soto, M., Herzog, C., Pacheco, J. A., Fujisaka, S., Bullock, K., Clish, C. B., & Kahn, C. R. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0086-5 · Cited by 216 · see citing works
“contents showed large differences of the composition of bacterial communities between the different groups [27] as”
BackgroundInfluentialInsulin action at a molecular level – 100 years of progress
White, M. F., & Kahn, C. R. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101304 · Cited by 214 · see citing works
“A number of metabolites have been shown to correlate with insulin resistance in both mice [261] and humans, and some, such as 2-aminoadipate, alphahydroxybutyrate, and N-acetylglycine, are suggested to be biomarkers of T2DM or insulin resistance [261e264].”
BackgroundIntestinal Barrier and Permeability in Health, Obesity and NAFLD
Portincasa, P., Bonfrate, L., Khalil, M., Angelis, M. D., Calabrese, F. M., D’Amato, M., Wang, D. Q. ‐., & Ciaula, A. D. (2021) · Biomedicines · doi:10.3390/biomedicines10010083 · Cited by 212 · see citing works
Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies
Duan, H., Yu, L., Tian, F., Zhai, Q., Fan, L., & Chen, W. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1843396 · Cited by 215 · see citing works
High fat diet, gut microbiome and gastrointestinal cancer
Tong, Y., Gao, H., Qi, Q., Liu, X., Li, J., Gao, J., Li, P., Wang, Y., Du, L., & Wang, C. (2021) · Theranostics · doi:10.7150/thno.56157 · Cited by 205 · see citing works
The gut microbiome: a core regulator of metabolism
Fujisaka, S., Watanabe, Y., & Tobe, K. (2022) · Journal of Endocrinology · doi:10.1530/joe-22-0111 · Cited by 217 · see citing works
Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Nicolas, G. R., & Chang, P. V. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.04.006 · Cited by 195 · see citing works
“Gut microbial L-carnitine metabolism is not limited to cardiovascular health and also correlates with insulin resistance [73].”
BackgroundShort‐chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells
Luu, M., & Visekruna, A. (2019) · European Journal of Immunology · doi:10.1002/eji.201848009 · Cited by 187 · see citing works
Horgusluoglu, E., Neff, R., Song, W., Wang, M., Wang, Q., Arnold, M., Krumsiek, J., Galindo‐Prieto, B., Ming, C., Nho, K., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12468 · Cited by 175 · see citing works
“13 Recent studies revealed that plasma phospholipids were associated with cognitive decline in mild cognitive impairment (MCI) and AD patients, 14 and altered sphingomyelin and ceramide levels were observed in the early stage of AD.”
A framework for examining how diet impacts tumour metabolism
Lien, E. C., & Vander Heiden, M. G. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0198-5 · Cited by 139 · see citing works
Horvath, T. D., Ihekweazu, F. D., Haidacher, S. J., Ruan, W. H., Engevik, K. A., Fultz, R., Hoch, K. M., Luna, R. A., Oezguen, N., Spinler, J. K., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104158 · Cited by 142 · see citing works
The Gut Microbiome in Pancreatic Disease
Akshintala, V. S., Talukdar, R., Singh, V. K., & Goggins, M. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.08.045 · Cited by 131 · see citing works
“The gut microbiome is known to have major effects on systemic metabolism,(6,7) but there are thousands of metabolites in the plasma and in the gut, many of which remain uncharacterized.(7) A large portion of the variance in fecal metabolites can be explained by the composition of the fecal microbiome.”
Addolorato, G., Ponziani, F. R., Dionisi, T., Mosoni, C., Vassallo, G. A., Sestito, L., Petito, V., Picca, A., Marzetti, E., Tarli, C., et al. (2020) · Liver International · doi:10.1111/liv.14383 · Cited by 125 · see citing works
Jacobs, J. P., Lagishetty, V., Hauer, M. C., Labus, J. S., Dong, T. S., Toma, R., Vuyisich, M., Naliboff, B. D., Lackner, J. M., Gupta, A., et al. (2023) · Microbiome · doi:10.1186/s40168-022-01450-5 · Cited by 123 · see citing works
The Potential of the Gut Microbiome to Reshape the Cancer Therapy Paradigm
Liu, L., & Shah, K. (2022) · JAMA Oncology · doi:10.1001/jamaoncol.2022.0494 · Cited by 113 · see citing works
Prattichizzo, F., Giuliani, A., Mensa’, E., Sabbatinelli, J., Nigris, V. D., Rippo, M. R., Sala, L. L., Procopio, A. D., Olivieri, F., & Ceriello, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.10.003 · Cited by 111 · see citing works
Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
de Jonge, P. A., Wortelboer, K., Scheithauer, T. P. M., van den Born, B. H., Zwinderman, A. H., Nóbrega, F. L., Dutilh, B. E., Nieuwdorp, M., & Herrema, H. (2022) · Nature Communications · doi:10.1038/s41467-022-31390-5 · Cited by 106 · see citing works
Montrose, D. C., Nishiguchi, R., Basu, S., Staab, H. A., Zhou, X. K., Wang, H., Meng, L., Johncilla, M. E., Cubillos‐Ruiz, J. R., Morales, D. K., et al. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.09.008 · Cited by 107 · see citing works
“This occurs, at least in part, by altering microbial nutrient sources, thus creating more or less favorable environments for certain species.(15,16) Several mechanisms can explain how microbes exert their effects on the intestinal tract, including through modulating levels and profiles of small molecules such as bile…”
BackgroundSmith, S. A., Ogawa, S. A., Chau, L., Whelan, K. A., Hamilton, K. E., Chen, J., Tan, L., Chen, E. Z., Keilbaugh, S. A., Fogt, F., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133371 · Cited by 105 · see citing works
“Indeed, antibiotic treatment of mice can increase fecal acylcarnitine levels (46), suggesting the interesting possibility that the IBD-associated dysbiosis may play a role in the elevation of fecal acylcarnitines due to reduced consumption.”
BackgroundKumar, M., Ji, B., Babaei, P., Das, P., Lappa, D., Ramakrishnan, G., Fox, T. E., Haque, R., Petri, W. A., Bäckhed, F., et al. (2018) · Metabolic Engineering · doi:10.1016/j.ymben.2018.07.018 · Cited by 103 · see citing works
“Additionally, several recent studies have shown that the gut microbiota metabolism impacts the level of plasma metabolites (Fujisaka et al., 2018; Krishnan et al., 2018; Org et al., 2017; Ottosson et al., 2018; Wikoff et al., 2009; Yano et al., 2015).”
BackgroundGuo, Y., Zhu, X., Zeng, M., Qi, L., Tang, X., Wang, D., Zhang, M., Xie, Y., Li, H., Yang, X., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01443-2 · Cited by 104 · see citing works
Han, M., Yang, K., Yang, P., Zhong, C., Chen, C., Wang, S., Lu, Q., & Ning, K. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1842991 · Cited by 100 · see citing works
Piazzon, M. C., Naya-Català, F., Perera, E., Palenzuela, O. R., Sitjà‐Bobadilla, A., & Pérez‐Sánchez, J. (2020) · Microbiome · doi:10.1186/s40168-020-00922-w · Cited by 87 · see citing works
C57BL/6J substrain differences in response to high-fat diet intervention
Siersbæk, M. S., Ditzel, N., Hejbøl, E. K., Præstholm, S. M., Markussen, L. K., Avolio, F., Li, L., Lehtonen, L., Hansen, A. K., Schrøder, H. D., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-70765-w · Cited by 86 · see citing works
Coras, R., Murillo‐Saich, J., & Gumá, M. (2020) · Cells · doi:10.3390/cells9040827 · Cited by 85 · see citing works
Damiani, F., Cornuti, S., & Tognini, P. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109491 · Cited by 87 · see citing works
“, 1987) and to be affected by different antibiotic treatments (Fujisaka et al., 2018).”
Metabolic support in the critically ill: a consensus of 19
Wernerman, J., Christopher, K. B., Annane, D., Casaer, M. P., Coopersmith, C. M., Deane, A. M., Waele, E. D., Elke, G., Ichaï, C., Karvellas, C. J., et al. (2019) · Critical Care · doi:10.1186/s13054-019-2597-0 · Cited by 84 · see citing works
“The gut microbiome has an increasingly recognized role in maintaining homeostasis [30].”
BackgroundMicrobial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders
Liu, M., Nieuwdorp, M., de Vos, W. M., & Rampanelli, E. (2022) · Metabolites · doi:10.3390/metabo12090834 · Cited by 79 · see citing works
Chronic kidney disease and gut microbiota
Khiabani, S. A., Asgharzadeh, M., & Kafil, H. S. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18991 · Cited by 76 · see citing works
Fujisaka, S., Usui, I., Nawaz, A., Igarashi, Y., Okabe, K., Furusawa, Y., Watanabe, S., Yamamoto, S., Sasahara, M., Watanabe, Y., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-62506-w · Cited by 74 · see citing works
Castro-Mejía, J. L., Khakimov, B., Krych, Ł., Bülow, J., Bechshøft, R. L., Højfeldt, G. W., Mertz, K. H., Garne, E. S., Schacht, S. R., Ahmad, H. F., et al. (2020) · Aging Cell · doi:10.1111/acel.13105 · Cited by 71 · see citing works
“%) signatures are important drivers of phenotypic differentiation (Figure 5) and also described in animal models (Fujisaka et al., 2018).”
BackgroundThe role of adipose tissue M1/M2 macrophages in type 2 diabetes mellitus
Fujisaka, S. (2020) · Diabetology International · doi:10.1007/s13340-020-00482-2 · Cited by 70 · see citing works
Elucidation of Gut Microbiota-Associated Lipids Using LC-MS/MS and 16S rRNA Sequence Analyses
Yasuda, S., Okahashi, N., Tsugawa, H., Ogata, Y., Ikeda, K., Suda, W., Arai, H., Hattori, M., & Arita, M. (2020) · iScience · doi:10.1016/j.isci.2020.101841 · Cited by 69 · see citing works
“The other part of AAHFA, namely a-hydroxy fatty acid, is potentially synthesized by bacterial CYP enzyme, which plays a role in oxygen detoxification in obligate anaerobic bacteria (Girhard et al., 2007).”
BackgroundNoecker, C. A., Chiu, H.-C., McNally, C. P., & Borenstein, E. (2019) · mSystems · doi:10.1128/msystems.00579-19 · Cited by 66 · see citing works
Determinants of nutrient limitation in cancer
Sullivan, M. R., & Heiden, M. G. V. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1611733 · Cited by 65 · see citing works
“The microbiome carries out many metabolic reactions, and can affect which nutrients in the diet end up in circulation, or produce metabolites that do not directly reflect the content of diet (LeBlanc et al. 2013; Fujisaka et al. 2018).”
BackgroundGao, H., Shu, Q., Chen, J., Fan, K., Xu, P., Zhou, Q., Li, C., & Zheng, H. X. (2019) · mSystems · doi:10.1128/msystems.00048-19 · Cited by 66 · see citing works
“important therapeutic approach in clinical practice, can adversely affect the gut microbiota, inevitably giving rise to metabolic disorders (19).”
BackgroundLuo, M., Cai, J., Luo, S., Hong, X., Xu, L., Lin, H., Chen, X., & Fu, W. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1142140 · Cited by 64 · see citing works
“Gut microbiota has been proved to be involved in the regulation of human metabolism and immune activities, and play an important role in maintaining the homeostasis (Musso et al., 2010; Maynard et al., 2012; Frosali et al., 2015; Fujisaka et al., 2018).”
BackgroundLei, M., Menon, R., Manteiga, S., Alden, N., Hunt, C. L., Alaniz, R. C., Lee, K., & Jayaraman, A. (2019) · mSystems · doi:10.1128/msystems.00724-19 · Cited by 62 · see citing works
“The total annotation 390 rate (204/5408) achieved in the present study is comparable to previous metabolomics studies on 391 the gut microbiota, which report annotation rates ranging from 2 (53) to 5% (54).”
ResultZhang, C., Li, Z., Zhang, C., Li, M., Lee, Y., & Zhang, G. (2019) · Nutrients · doi:10.3390/nu11051181 · Cited by 60 · see citing works
“Certain polysaccharides generally exhibit multiple biological activities [38].”
BackgroundMa, H., Hu, Y., Zhang, B., Shao, Z., Roura, E., & Wang, S. (2021) · Food Science and Human Wellness · doi:10.1016/j.fshw.2021.07.002 · Cited by 60 · see citing works
From bugs to brain: unravelling the GABA signalling networks in the brain–gut–microbiome axis
Belelli, D., Lambert, J. J., Wan, M. L. Y., Monteiro, A. R., Nutt, D., & Swinny, J. D. (2024) · Brain · doi:10.1093/brain/awae413 · Cited by 67 · see citing works
“148 This finding was corroborated by (i) the observation that faecal GABA levels are decreased by antibiotic use 149 and (ii) genetic analysis of the bacterial community in mammalian gut isolates.”
Rampanelli, E., Romp, N., Troise, A. D., Ananthasabesan, J., Wu, H., Gül, I. S., Pascale, S. D., Scaloni, A., Bäckhed, F., Fogliano, V., et al. (2025) · Microbiome · doi:10.1186/s40168-024-02002-9 · Cited by 60 · see citing works
“Diet, the human microbiome, and host genetics are determinants of metabolic status, in part through the production of metabolites via fermentation of dietary components by the gut microbiota [1, 2].”
Koopman, N., Molinaro, A., Nieuwdorp, M., & Holleboom, A. G. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15416 · Cited by 57 · see citing works
Dey, P., Chaudhuri, S. R., Efferth, T., & Pal, S. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.09.026 · Cited by 55 · see citing works
Multi-Omics Analysis Reveals Aberrant Gut-Metabolome-Immune Network in Schizophrenia
Fan, Y., Gao, Y., Ma, Q., Yang, Z., Zhao, B., He, X., Yang, J., Yan, B., Gao, F., Li, Q., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.812293 · Cited by 56 · see citing works
Mora-Ortiz, M., Ramos, P. N., Oregioni, A., & Claus, S. P. (2019) · Metabolomics · doi:10.1007/s11306-019-1548-8 · Cited by 53 · see citing works
Microbial modulation of the gut microbiome for treating autoimmune diseases
Balakrishnan, B., & Taneja, V. (2018) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2018.1517044 · Cited by 51 · see citing works
Bodywide ecological interventions on cancer
Kroemer, G., McQuade, J. L., Mérad, M., André, F., & Zitvogel, L. (2023) · Nature Medicine · doi:10.1038/s41591-022-02193-4 · Cited by 51 · see citing works
Gut Biofactory—Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review
Skonieczna‐Żydecka, K., Jakubczyk, K., Maciejewska, D., Janda, K., Kaźmierczak-Siedlecka, K., Kaczmarczyk, M., Łoniewski, I., & Marlicz, W. M. (2020) · Nutrients · doi:10.3390/nu12113369 · Cited by 50 · see citing works
“GABA derived from gut were shown to cross the BBB [69,70] and its synthesis depends on antibiotic exposure [71] and on diet, as high fat food intake lowered the GABA levels in the rat prefrontal cortex.”
BackgroundCashew apple fiber prevents high fat diet-induced obesity in mice: an NMR metabolomic evaluation
Carvalho, D. V., Silva, L. K. D. F., Filho, E. G. A., Santos, F. A., de Lima, R. P., Viana, A. F. S. C., Nunes, P. I. G., Fonseca, S. G. D. C., de Melo, T. S., Viana, D. D. A., et al. (2019) · Food & Function · doi:10.1039/c8fo01575a · Cited by 49 · see citing works
Moriano‐Gutierrez, S., Koch, E. J., Bussan, H. E., Romano, K. A., Belcaid, M., Rey, F. E., Ruby, E. G., & McFall‐Ngai, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1819897116 · Cited by 47 · see citing works
“The first is a chemical signal, such as a bacterial metabolite, delivered through the circulation (63, 64); one such metabolite, acetate, is generated in the light organ as byproduct of symbiont metabolism (34).”
BackgroundNovel strategies for clinical investigation and biomarker discovery: a guide to applied metabolomics
Carneiro, G. R. A., Radcenco, A. L., Evaristo, J. A. M., & Monnerat, G. (2019) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0045 · Cited by 44 · see citing works
A system biology perspective on environment–host–microbe interactions
Chen, L., Garmaeva, S., Zhernakova, A., Fu, J., & Wijmenga, C. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy137 · Cited by 44 · see citing works
Dong, F., Jiang, S., Tang, C., Wang, X., Ren, X., Wei, Q., Tian, J., Hu, W., Guo, J. Z., Fu, X., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.11.010 · Cited by 44 · see citing works
Gestational Insulin Resistance Is Mediated by the Gut Microbiome–Indoleamine 2,3-Dioxygenase Axis
Priyadarshini, M., Navarro, G., Reiman, D. J., Sharma, A., Xu, K., Lednovich, K., Manzella, C. R., Khan, M. W., Garcia, M. S., Allard, S. M., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.01.008 · Cited by 42 · see citing works
The Many Faces of Microbiota-Gut-Brain Axis in Autism Spectrum Disorder
Gonçalves, C. L., Doifode, T., Rezende, V. L., Costa, M. A., Rhoads, J. M., & Soutullo, C. A. (2024) · Life Sciences · doi:10.1016/j.lfs.2023.122357 · Cited by 42 · see citing works
Li, X., Hou, H., Chen, H., Liu, X., Wang, J., Yang, Q., & He, G. (2020) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2020.01.079 · Cited by 41 · see citing works
Watanabe, Y., Fujisaka, S., Morinaga, Y., Watanabe, S., Nawaz, A., Hatta, H., Kado, T., Nishimura, A., Bilal, M., Aslam, M. R., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101797 · Cited by 40 · see citing works
“As these metabolites have been suggested to improve insulin resistance in previous studies, these changes may improve glucose metabolism by IX [25 e 27].”
BackgroundMethodResultMatute, J. D., Duan, J., Flak, M. B., Griebel, P., Tascón-Arcila, J., Doms, S., Hanley, T., Antanaviciute, A., Gundrum, J., Welch, J. L. M., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20211938 · Cited by 37 · see citing works
“A multiplexed amplicon library covering the 16S rDNA gene V4 region was generated from DNA-extracted samples, and reads were generated on the MiSeq instrument from the amplicon library as previously described (Fujisaka et al., 2018).”
MethodOutside the liver box: The gut microbiota as pivotal modulator of liver diseases
Wahlstrom, A. M. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.07.004 · Cited by 35 · see citing works
Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid
Zheng, N., Gu, Y., Hong, Y., Sheng, L., Chen, L.-L., Zhang, F., Hou, J., Zhang, W.-D., Zhang, Z.-A., Jia, W., et al. (2019) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2019.11.003 · Cited by 29 · see citing works
Microbial-driven genetic variation in holobionts
Zilber‐Rosenberg, I., & ROSENBERG, E. B. (2021) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuab022 · Cited by 36 · see citing works
Gut dysbiosis and metabolic diseases
Bandopadhyay, P., & Ganguly, D. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2022.06.031 · Cited by 37 · see citing works
Metabolic adaptation to calorie restriction
Guijas, C., Montenegro-Burke, J. R., Cintrón-Colón, R., Domingo-Almenara, X., Sánchez-Alavez, M., Aguirre, C., Shankar, K., Majumder, E. L. ‐., Billings, E., Conti, B., et al. (2020) · Science Signaling · doi:10.1126/scisignal.abb2490 · Cited by 35 · see citing works
“However, plasma metabolomics should have captured most of the changes introduced by the microbiome in our model, and several models that characterize the plasma metabolome use it as a surrogate measure of microbiome changes (53, 54).”
Best Practices for Microbiome Study Design in Companion Animal Research
Jarett, J. K., Kingsbury, D. D., Dahlhausen, K. E., & Ganz, H. H. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.644836 · Cited by 34 · see citing works
Microbiome and Metabolomics in Liver Cancer: Scientific Technology
Ganesan, R., Yoon, S. J., & Suk, K. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010537 · Cited by 34 · see citing works
Impact of diet and host genetics on the murine intestinal mycobiome
Gupta, Y., Ernst, A. L., Vorobyev, A., Beltsiou, F., Zillikens, D., Bieber, K., Sanna‐Cherchi, S., Christiano, A. M., Sadik, C. D., Ludwig, R. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36479-z · Cited by 32 · see citing works
Acuña, I., Ruiz-Rodriguez, A., Cerdó, T., Cantarero, S., López‐Moreno, A., Aguilera, J., Campoy, C., & Suárez, A. (2021) · BioFactors · doi:10.1002/biof.1766 · Cited by 31 · see citing works
Wen, Y., Peng, L., Xu, R., Zang, N., Huang, Q., & Zhong, M. (2018) · Pregnancy Hypertension · doi:10.1016/j.preghy.2018.12.001 · Cited by 32 · see citing works
Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis
Amin, U., Jiang, R., Raza, S. M., Fan, M., Liang, L., Feng, N., Li, X., Yang, Y., & Guo, F. (2023) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2023.06.002 · Cited by 29 · see citing works
“28 Moreover, GABA produced by GM modulates abdominal pain and visceral sensitivity.”
BackgroundNiska-Blakie, J., Gopinathan, L., Low, K. N., Kien, Y. L., Goh, C. M. F., Caldez, M. J., Pfeiffenberger, E., Jones, O. S., Ong, C. B., Kurochkin, I. V., et al. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03359-z · Cited by 28 · see citing works
Li, G., Tong, Y., Xiao, Y., Huang, S., Zhao, T., & Xia, X. (2023) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2023.109712 · Cited by 29 · see citing works
Mercer, K. E., Yeruva, L., Pack, L., Graham, J. L., Stanhope, K. L., Chintapalli, S. V., Wankhade, U. D., Shankar, K., Havel, P. J., Adams, S. H., et al. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00105.2020 · Cited by 27 · see citing works
“These findings concur with previous reports that have documented differences in microbial composition due to disparate mouse genetics (9, 16, 17, 34, 42, 53).”
ResultDing, Q., Tian, J., Li, M., Lian, F., Zhao, L., Wei, X., Han, L., Zheng, Y., Gao, Z., Yang, H., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.530160 · Cited by 28 · see citing works
“Moreover, levels of Firmicutes (e.g., Clostridium perfringens) have been shown to decrease in metformin-treated patients (Karlsson et al., 2013), which in turn can alter bile acid metabolism by reducing the circulating levels of pro-inflammatory bile acids (DCA and TDCA) (Fujisaka et al., 2018).”
BackgroundGolonka, R., & Vijay-Kumar, M. (2021) · Advances in Cancer Research · doi:10.1016/bs.acr.2020.10.004 · Cited by 21 · see citing works
Luo, Y., Zhao, P., Dou, M., Mao, J., Zhang, G., Su, Y., Wang, Q., Wang, Q., Wang, Y., Sun, R., et al. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108563 · Cited by 26 · see citing works
Yin, X., Prendiville, O., McNamara, A. E., & Brennan, L. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00440 · Cited by 26 · see citing works
Gut Microbiota Regulate Pancreatic Growth, Exocrine Function, and Gut Hormones
Girdhar, K., Soto, M., Huang, Q., Orliaguet, L., Cederquist, C., Sundaresh, B., Hu, J., Figura, M., Raisingani, A., Canfora, E. E., et al. (2022) · Diabetes · doi:10.2337/db21-0382 · Cited by 26 · see citing works
The microbiota-gut-brain axis in pathogenesis of depression: A narrative review
Yao, H., Zhang, D., Yu, H., Shen, H., Liu, H., Meng, F., Wu, X., Zhang, G., & Wang, X. (2022) · Physiology & Behavior · doi:10.1016/j.physbeh.2022.114056 · Cited by 31 · see citing works
Heat-killed Akkermansia muciniphila ameliorates allergic airway inflammation in mice
Yoon, S. A., Lim, Y., Byeon, H. R., Jung, J.-Y., Ma, S., Hong, M.-G., Kim, D., Song, E., Nam, Y., Seo, J., et al. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1386428 · Cited by 25 · see citing works
Metabolomic‐Based Approach to Identify Biomarkers of Apple Intake
McNamara, A. E., Collins, C., Harsha, P. S. C. S., González-Peña, D., Gibbons, H., McNulty, B. A., Nugent, A. P., Walton, J., Flynn, A., & Brennan, L. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201901158 · Cited by 25 · see citing works
Zhang, Z., Cao, X.-C., Peng, J., Huang, S. L., Chen, C., Jia, S.-Z., Ni, J., & Song, G.-L. (2022) · Antioxidants · doi:10.3390/antiox11050829 · Cited by 25 · see citing works
“The LC–MS experiment and analyses of untargeted metabolomics were performed as described previously [22].”
MethodProbiotics and Prebiotics in the Treatment of Autism Spectrum Disorder: A Narrative Review
Zhang, S., Han, F., Wang, Q., & Fan, F. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2301020 · Cited by 24 · see citing works
Braga, J. D., Yang, Y., Nagao, T., Katô, N., Yanaka, N., Nishio, K., Okada, M., Kuroda, M., Yamaguchi, S., & Kumrungsee, T. (2025) · npj Science of Food · doi:10.1038/s41538-025-00383-1 · Cited by 23 · see citing works
Potential of food intake biomarkers in nutrition research
McNamara, A. E., & Brennan, L. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120007053 · Cited by 23 · see citing works
“The human metabolome is influenced by multiple factors such as genetics, the microbiome((18)) and environmental factors including diet and lifestyle((19)).”
Background
- Authors
- Fujisaka, S., Avila-Pacheco, J., Soto, M., Kostic, A., Dreyfuss, J. M., Pan, H., Ussar, S., Altindis, E., Li, N., Bry, L., Clish, C. B., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Boston University (US)
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Kahn, C. Ronald
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 22
- Issue
- 11
- Pages
- 3072-3086
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5880543
- OpenAlex
- W2790304967
- Cited by
- 231
- References
- 51
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 29 · 2023: 25 · 2022: 37 · 2021: 29 · 2020: 33 · 2019: 23 · 2018: 14
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (R01DK031036, R01DK033201)
- Diabetes Research Center (P30DK036836)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- gut microbiota, plasma metabolites, high-fat diet, insulin resistance, host genetic background, vancomycin, metronidazole, antibiotic effects on microbiota, cecal metabolites, C57BL/6J mice, mouse strains, metabolomics
- MeSH terms
- Gastrointestinal Microbiome, Animals, Humans, Obesity, Mice, Metabolomics, Diet, High-Fat
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