{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T19:09:41Z","timestamp":1769195381453,"version":"3.49.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20H04109"],"award-info":[{"award-number":["20H04109"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression. Fecal samples collected from control and NASH-HCC model STAM mice were subjected to headspace autosampler gas chromatography-electron ionization-mass spectrometry. Non-target profiling analysis identified diacetyl (2,3-butandione) as a fecal VOC that characterizes STAM mice. Although fecal diacetyl levels were correlated with the HCC in STAM mice, diacetyl is known as a cytotoxic\/tissue-damaging compound rather than genotoxic or mutagenic; therefore, we examined the effect of bioactivity associated with NASH progression. We observed that diacetyl induced several pro-inflammatory molecules, including tumor necrosis factor-\u03b1, cyclooxygenase-2, monocyte chemoattractant protein-1, and transforming growth factor-\u03b2, in mouse macrophage RAW264.7 and Kupffer KPU5 cells. Additionally, we observed that diacetyl induced \u03b1-smooth muscle actin, one of the hallmarks of fibrosis, in an ex vivo cultured hepatic section, but not in in vitro hepatic stellate TWNT-1 cells. These results suggest that diacetyl would be a potential biomarker of fecal VOC in STAM mice, and its ability to trigger the macrophage-derived inflammation and fibrosis may partly contribute to NASH-HCC carcinogenesis.<\/jats:p>","DOI":"10.1038\/s41598-023-36091-7","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T14:02:21Z","timestamp":1685628141000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Non-target GC\u2013MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice"],"prefix":"10.1038","volume":"13","author":[{"given":"Mai","family":"Kato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momoka","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Ooka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuji","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Onoda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Tsunematsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasukiyo","family":"Yoshioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumio","family":"Hayakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumiko","family":"Shoji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Shoji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"36091_CR1","unstructured":"WHO. Obesity and overweight. Fact sheet (2018)."},{"key":"36091_CR2","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","volume":"15","author":"M Bl\u00fcher","year":"2019","unstructured":"Bl\u00fcher, M. Obesity: Global epidemiology and pathogenesis. Nat. Rev. Endocrinol. 15, 288\u2013298 (2019).","journal-title":"Nat. Rev. Endocrinol."},{"key":"36091_CR3","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1056\/NEJMsr1606602","volume":"375","author":"B Lauby-Secretan","year":"2016","unstructured":"Lauby-Secretan, B. et al. Body fatness and cancer-viewpoint of the IARC Working Group. N. Engl. J. Med. 375, 794\u2013798 (2016).","journal-title":"N. Engl. J. Med."},{"key":"36091_CR4","doi-asserted-by":"publisher","first-page":"601710","DOI":"10.3389\/fonc.2020.601710","volume":"10","author":"D Suresh","year":"2020","unstructured":"Suresh, D., Srinivas, A. N. & Kumar, D. P. Etiology of hepatocellular carcinoma: Special focus on fatty liver disease. Front. Oncol. 10, 601710 (2020).","journal-title":"Front. Oncol."},{"key":"36091_CR5","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1056\/NEJM199701303360507","volume":"336","author":"JH Hoofnagle","year":"1997","unstructured":"Hoofnagle, J. H. & di Bisceglie, A. M. The treatment of chronic viral hepatitis. N. Engl. J. Med. 336, 347\u2013356 (1997).","journal-title":"N. Engl. J. Med."},{"key":"36091_CR6","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41575-019-0145-7","volume":"16","author":"QM Anstee","year":"2019","unstructured":"Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O. & Heikenwalder, M. From NASH to HCC: Current concepts and future challenges. Nat. Rev. Gastroenterol. Hepatol. 16, 411\u2013428 (2019).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"Suppl 1","key":"36091_CR7","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/liv.14362","volume":"40","author":"F Negro","year":"2020","unstructured":"Negro, F. Natural history of NASH and HCC. Liver Int. 40(Suppl 1), 72\u201376 (2020).","journal-title":"Liver Int."},{"key":"36091_CR8","first-page":"158","volume":"9","author":"A Safaei","year":"2016","unstructured":"Safaei, A. et al. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases. Gastroenterol. Hepatol. from bed to bench 9, 158\u2013173 (2016).","journal-title":"Gastroenterol. Hepatol. from bed to bench"},{"key":"36091_CR9","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1080\/14712598.2018.1518424","volume":"18","author":"V Delaune","year":"2018","unstructured":"Delaune, V. et al. Fecal microbiota transplantation: A promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response. Expert Opin. Biol. Ther. 18, 1061\u20131071 (2018).","journal-title":"Expert Opin. Biol. Ther."},{"key":"36091_CR10","unstructured":"Rodionova, E. I. et al. Detection of volatile organic compounds associated with hepatocellular carcinoma by macrosmatic animals: Approaches to the search for new tumor markers. Izv. Akad. Nauk. Seriia Biol. 293\u2013301."},{"key":"36091_CR11","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.3748\/wjg.v22.i4.1639","volume":"22","author":"DK Chan","year":"2016","unstructured":"Chan, D. K., Leggett, C. L. & Wang, K. K. Diagnosing gastrointestinal illnesses using fecal headspace volatile organic compounds. World J. Gastroenterol. 22, 1639\u20131649 (2016).","journal-title":"World J. Gastroenterol."},{"key":"36091_CR12","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1097\/MIB.0b013e31829a91f6","volume":"19","author":"C Walton","year":"2013","unstructured":"Walton, C. et al. Analysis of volatile organic compounds of bacterial origin in chronic gastrointestinal diseases. Inflamm. Bowel Dis. 19, 2069\u20132078 (2013).","journal-title":"Inflamm. Bowel Dis."},{"key":"36091_CR13","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1096\/fj.06-6927com","volume":"21","author":"CE Garner","year":"2007","unstructured":"Garner, C. E. et al. Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease. FASEB J. 21, 1675\u20131688 (2007).","journal-title":"FASEB J."},{"key":"36091_CR14","doi-asserted-by":"publisher","first-page":"2468","DOI":"10.1093\/ibd\/izy151","volume":"24","author":"S Bosch","year":"2018","unstructured":"Bosch, S. et al. Differentiation between pediatric irritable bowel syndrome and inflammatory Bowel disease based on fecal scent: Proof of principle study. Inflamm. Bowel Dis. 24, 2468\u20132475 (2018).","journal-title":"Inflamm. Bowel Dis."},{"key":"36091_CR15","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1586\/1744666X.2014.943664","volume":"10","author":"CSJ Probert","year":"2014","unstructured":"Probert, C. S. J., Reade, S. & Ahmed, I. Fecal volatile organic compounds: A novel, cheaper method of diagnosing inflammatory bowel disease?. Expert Rev. Clin. Immunol. 10, 1129\u20131131 (2014).","journal-title":"Expert Rev. Clin. Immunol."},{"key":"36091_CR16","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1042\/BST0391079","volume":"39","author":"CSJ Probert","year":"2011","unstructured":"Probert, C. S. J. Role of faecal gas analysis for the diagnosis of IBD. Biochem. Soc. Trans. 39, 1079\u20131080 (2011).","journal-title":"Biochem. Soc. Trans."},{"key":"36091_CR17","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.cgh.2017.09.055","volume":"16","author":"M Rossi","year":"2018","unstructured":"Rossi, M. et al. Volatile organic compounds in feces associate with response to dietary intervention in patients with irritable bowel syndrome. Clin. Gastroenterol. Hepatol. 16, 385-391.e1 (2018).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"36091_CR18","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1093\/ibd\/izx061","volume":"24","author":"NA Kennedy","year":"2018","unstructured":"Kennedy, N. A. et al. The impact of NOD2 variants on fecal microbiota in Crohn\u2019s disease and controls without gastrointestinal disease. Inflamm. Bowel Dis. 24, 583\u2013592 (2018).","journal-title":"Inflamm. Bowel Dis."},{"key":"36091_CR19","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1111\/codi.13271","volume":"18","author":"M Di Lena","year":"2016","unstructured":"Di Lena, M., Porcelli, F. & Altomare, D. F. Volatile organic compounds as new biomarkers for colorectal cancer: A review. Colorectal Dis. 18, 654\u2013663 (2016).","journal-title":"Colorectal Dis."},{"key":"36091_CR20","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1002\/ijc.28446","volume":"134","author":"TG de Meij","year":"2014","unstructured":"de Meij, T. G. et al. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: Proof of principle study. Int. J. cancer 134, 1132\u20131138 (2014).","journal-title":"Int. J. cancer"},{"key":"36091_CR21","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.jpeds.2015.05.044","volume":"167","author":"TGJ de Meij","year":"2015","unstructured":"de Meij, T. G. J. et al. Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis. J. Pediatr. 167, 562\u20137.e1 (2015).","journal-title":"J. Pediatr."},{"key":"36091_CR22","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1097\/MPG.0b013e3181a3bfbc","volume":"49","author":"CE Garner","year":"2009","unstructured":"Garner, C. E. et al. Analysis of faecal volatile organic compounds in preterm infants who develop necrotising enterocolitis: A pilot study. J. Pediatr. Gastroenterol. Nutr. 49, 559\u2013565 (2009).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"36091_CR23","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.cgh.2013.04.016","volume":"11","author":"J Boursier","year":"2013","unstructured":"Boursier, J., Rawls, J. F. & Diehl, A. M. Obese humans with nonalcoholic fatty liver disease display alterations in fecal microbiota and volatile organic compounds. Clin. Gastroenterol. Hepatol. 11, 876\u2013878 (2013).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"36091_CR24","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jnutbio.2018.03.009","volume":"57","author":"C Goswami","year":"2018","unstructured":"Goswami, C., Iwasaki, Y. & Yada, T. Short-chain fatty acids suppress food intake by activating vagal afferent neurons. J. Nutr. Biochem. 57, 130\u2013135 (2018).","journal-title":"J. Nutr. Biochem."},{"key":"36091_CR25","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.cmet.2014.07.006","volume":"20","author":"MT Khan","year":"2014","unstructured":"Khan, M. T., Nieuwdorp, M. & B\u00e4ckhed, F. Microbial modulation of insulin sensitivity. Cell Metab. 20, 753\u2013760 (2014).","journal-title":"Cell Metab."},{"key":"36091_CR26","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.cell.2013.12.016","volume":"156","author":"F De Vadder","year":"2014","unstructured":"De Vadder, F. et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84\u201396 (2014).","journal-title":"Cell"},{"key":"36091_CR27","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1136\/gutjnl-2014-307913","volume":"64","author":"ES Chambers","year":"2015","unstructured":"Chambers, E. S. et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 64, 1744\u20131754 (2015).","journal-title":"Gut"},{"key":"36091_CR28","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nm.3779","volume":"21","author":"C Tang","year":"2015","unstructured":"Tang, C. et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat. Med. 21, 173\u2013177 (2015).","journal-title":"Nat. Med."},{"key":"36091_CR29","doi-asserted-by":"publisher","first-page":"3203","DOI":"10.2337\/db14-1938","volume":"64","author":"JC McNelis","year":"2015","unstructured":"McNelis, J. C. et al. GPR43 potentiates \u03b2-cell function in obesity. Diabetes 64, 3203\u20133217 (2015).","journal-title":"Diabetes"},{"key":"36091_CR30","doi-asserted-by":"publisher","first-page":"5326","DOI":"10.1038\/s41598-022-08678-z","volume":"12","author":"T Sukaram","year":"2022","unstructured":"Sukaram, T. et al. Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma. Sci. Rep. 12, 5326 (2022).","journal-title":"Sci. Rep."},{"key":"36091_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00795-013-0016-1","volume":"46","author":"M Fujii","year":"2013","unstructured":"Fujii, M. et al. A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. Med. Mol. Morphol. 46, 141\u2013152 (2013).","journal-title":"Med. Mol. Morphol."},{"key":"36091_CR32","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.3748\/wjg.v18.i19.2300","volume":"18","author":"Y Takahashi","year":"2012","unstructured":"Takahashi, Y., Soejima, Y. & Fukusato, T. Animal models of nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis. World J. Gastroenterol. 18, 2300\u20132308 (2012).","journal-title":"World J. Gastroenterol."},{"key":"36091_CR33","doi-asserted-by":"publisher","first-page":"5681","DOI":"10.1038\/s41598-020-62541-7","volume":"10","author":"M Uchikawa","year":"2020","unstructured":"Uchikawa, M. et al. Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-Ay mice. Sci. Rep. 10, 5681 (2020).","journal-title":"Sci. Rep."},{"key":"36091_CR34","doi-asserted-by":"publisher","first-page":"5125","DOI":"10.1038\/s41598-017-04989-8","volume":"7","author":"R Ahmad","year":"2017","unstructured":"Ahmad, R., Rah, B., Bastola, D., Dhawan, P. & Singh, A. B. Obesity-induces organ and tissue specific tight junction restructuring and barrier deregulation by claudin switching. Sci. Rep. 7, 5125 (2017).","journal-title":"Sci. Rep."},{"key":"36091_CR35","doi-asserted-by":"publisher","unstructured":"NTP Technical Report on the Toxicology and Carcinogenesis Studies of 2,3-Butanedione (CAS NO. 431-03-8) in Wistar Han [Crl:WI (Han)] Rats and B6C3F1\/N Mice (Inhalation Studies) https:\/\/ntp.niehs.nih.gov\/go\/tr593abs (2018) https:\/\/doi.org\/10.22427\/NTP-TR-593.","DOI":"10.22427\/NTP-TR-593"},{"key":"36091_CR36","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1111\/febs.13665","volume":"283","author":"I Fabregat","year":"2016","unstructured":"Fabregat, I. et al. TGF-\u03b2 signalling and liver disease. FEBS J. 283, 2219\u20132232 (2016).","journal-title":"FEBS J."},{"key":"36091_CR37","doi-asserted-by":"publisher","first-page":"357","DOI":"10.3389\/fonc.2018.00357","volume":"8","author":"I Fabregat","year":"2018","unstructured":"Fabregat, I. & Caballero-D\u00edaz, D. Transforming growth factor-\u03b2-induced cell plasticity in liver fibrosis and hepatocarcinogenesis. Front. Oncol. 8, 357 (2018).","journal-title":"Front. Oncol."},{"key":"36091_CR38","doi-asserted-by":"publisher","first-page":"4048","DOI":"10.1021\/jf500615u","volume":"62","author":"T Shibamoto","year":"2014","unstructured":"Shibamoto, T. Diacetyl: Occurrence, analysis, and toxicity. J. Agric. Food Chem. 62, 4048\u20134053 (2014).","journal-title":"J. Agric. Food Chem."},{"key":"36091_CR39","doi-asserted-by":"publisher","first-page":"e111833","DOI":"10.1371\/journal.pone.0111833","volume":"9","author":"T Hara","year":"2014","unstructured":"Hara, T., Matsui, H. & Shimizu, H. Suppression of microbial metabolic pathways inhibits the generation of the human body odor component diacetyl by Staphylococcus spp. PLoS ONE 9, e111833 (2014).","journal-title":"PLoS ONE"},{"key":"36091_CR40","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1093\/oxfordjournals.jbchem.a021230","volume":"119","author":"M Otsuka","year":"1996","unstructured":"Otsuka, M., Mine, T., Ohuchi, K. & Ohmori, S. A detoxication route for acetaldehyde: Metabolism of diacetyl, acetoin, and 2,3-butanediol in liver homogenate and perfused liver of rats. J. Biochem. 119, 246\u2013251 (1996).","journal-title":"J. Biochem."},{"key":"36091_CR41","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.jhep.2008.03.007","volume":"48","author":"J Siebler","year":"2008","unstructured":"Siebler, J., Galle, P. R. & Weber, M. M. The gut-liver-axis: Endotoxemia, inflammation, insulin resistance and NASH. J. Hepatol. 48, 1032\u20131034 (2008).","journal-title":"J. Hepatol."},{"key":"36091_CR42","doi-asserted-by":"publisher","first-page":"G911","DOI":"10.1152\/ajpgi.00225.2013","volume":"305","author":"H Okubo","year":"2013","unstructured":"Okubo, H. et al. Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G911\u2013G918 (2013).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"36091_CR43","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/toxsci\/kfn016","volume":"103","author":"DL Morgan","year":"2008","unstructured":"Morgan, D. L., Flake, G. P., Kirby, P. J. & Palmer, S. M. Respiratory toxicity of diacetyl in C57BL\/6 mice. Toxicol. Sci. 103, 169\u2013180 (2008).","journal-title":"Toxicol. Sci."},{"key":"36091_CR44","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.3109\/08958370902795311","volume":"21","author":"ST Larsen","year":"2009","unstructured":"Larsen, S. T., Alarie, Y., Hammer, M. & Nielsen, G. D. Acute airway effects of diacetyl in mice. Inhal. Toxicol. 21, 1123\u20131128 (2009).","journal-title":"Inhal. Toxicol."},{"key":"36091_CR45","first-page":"87","volume":"65","author":"B Starek-Swiechowicz","year":"2014","unstructured":"Starek-Swiechowicz, B. & Starek, A. Diacetyl exposure as a pneumotoxic factor: A review. Rocz. Panstw. Zakl. Hig. 65, 87\u201392 (2014).","journal-title":"Rocz. Panstw. Zakl. Hig."},{"key":"36091_CR46","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1093\/toxsci\/kfq067","volume":"115","author":"SE Anderson","year":"2010","unstructured":"Anderson, S. E., Jackson, L. G., Franko, J. & Wells, J. R. Evaluation of dicarbonyls generated in a simulated indoor air environment using an in vitro exposure system. Toxicol. Sci. 115, 453\u2013461 (2010).","journal-title":"Toxicol. Sci."},{"key":"36091_CR47","doi-asserted-by":"publisher","first-page":"786","DOI":"10.4103\/0973-1482.147692","volume":"11","author":"EA Bayomi","year":"2015","unstructured":"Bayomi, E. A. et al. Cyclooxygenase-2 expression is associated with elevated aspartate aminotransferase level in hepatocellular carcinoma. J. Cancer Res. Ther. 11, 786\u2013792 (2015).","journal-title":"J. Cancer Res. Ther."},{"key":"36091_CR48","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/hep.21108","volume":"43","author":"J Yu","year":"2006","unstructured":"Yu, J. et al. COX-2 induction in mice with experimental nutritional steatohepatitis: Role as pro-inflammatory mediator. Hepatology 43, 826\u2013836 (2006).","journal-title":"Hepatology"},{"key":"36091_CR49","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1158\/2159-8290.CD-16-0932","volume":"7","author":"TM Loo","year":"2017","unstructured":"Loo, T. M. et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov. 7, 522\u2013538 (2017).","journal-title":"Cancer Discov."},{"key":"36091_CR50","first-page":"2668","volume":"11","author":"Y Luo","year":"2019","unstructured":"Luo, Y. et al. Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice. Am. J. Transl. Res. 11, 2668\u20132682 (2019).","journal-title":"Am. J. Transl. Res."},{"key":"36091_CR51","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.3892\/or.2015.3745","volume":"33","author":"Y Yoshimine","year":"2015","unstructured":"Yoshimine, Y. et al. Hepatic expression of the Sptlc3 subunit of serine palmitoyltransferase is associated with the development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis. Oncol. Rep. 33, 1657\u20131666 (2015).","journal-title":"Oncol. Rep."},{"key":"36091_CR52","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1016\/j.bbadis.2016.04.005","volume":"1862","author":"DT Reid","year":"2016","unstructured":"Reid, D. T. et al. Unique microbial-derived volatile organic compounds in portal venous circulation in murine non-alcoholic fatty liver disease. Biochim. Biophys. Acta 1862, 1337\u20131344 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"36091_CR53","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/0027-5107(92)90212-K","volume":"269","author":"L Dorado","year":"1992","unstructured":"Dorado, L., Ruis Montoya, M. R. & Rodr\u00edguez Mellado, J. M. A contribution to the study of the structure-mutagenicity relationship for alpha-dicarbonyl compounds using the Ames test. Mutat. Res. 269, 301\u2013306 (1992).","journal-title":"Mutat. Res."},{"key":"36091_CR54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1476-9255-7-15","volume":"7","author":"AL Harte","year":"2010","unstructured":"Harte, A. L. et al. Elevated endotoxin levels in non-alcoholic fatty liver disease. J. Inflamm. 7, 15 (2010).","journal-title":"J. Inflamm."},{"key":"36091_CR55","doi-asserted-by":"publisher","first-page":"770986","DOI":"10.3389\/fendo.2021.770986","volume":"12","author":"T Kessoku","year":"2021","unstructured":"Kessoku, T. et al. Endotoxins and non-alcoholic fatty liver disease. Front. Endocrinol. 12, 770986 (2021).","journal-title":"Front. Endocrinol."},{"key":"36091_CR56","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1136\/gut.2008.165886","volume":"58","author":"PD Cani","year":"2009","unstructured":"Cani, P. D. et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58, 1091\u20131103 (2009).","journal-title":"Gut"},{"key":"36091_CR57","doi-asserted-by":"publisher","first-page":"6479","DOI":"10.1038\/s41598-020-63627-y","volume":"10","author":"S Sanada","year":"2020","unstructured":"Sanada, S. et al. Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob\/ob mice. Sci. Rep. 10, 6479 (2020).","journal-title":"Sci. Rep."},{"key":"36091_CR58","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","volume":"7","author":"JG Caporaso","year":"2010","unstructured":"Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335\u2013336 (2010).","journal-title":"Nat. Methods"},{"key":"36091_CR59","doi-asserted-by":"publisher","first-page":"127789","DOI":"10.1016\/j.foodchem.2020.127789","volume":"337","author":"Y Kato","year":"2021","unstructured":"Kato, Y. et al. Methylglyoxal binds to amines in honey matrix and 2\u2032-methoxyacetophenone is released in gaseous form into the headspace on the heating of manuka honey. Food Chem. 337, 127789 (2021).","journal-title":"Food Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-36091-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-36091-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-36091-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T15:11:59Z","timestamp":1685632319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-36091-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["36091"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-36091-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"23 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8924"}}