{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:17:52Z","timestamp":1778221072296,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The increasing prevalence of metabolism-associated fatty liver disease (MAFLD) is associated with environmental pollutants and dietary factors, yet the synergistic effect and underlying mechanism of silica nanoparticles (SiNP) and a high-fat diet (HFD) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study aimed to investigate the role of the gut\u2013liver axis in MAFLD pathogenesis induced by co-exposure to SiNP and HFD, utilizing a multi-omics approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we found that combined SiNP and HFD exposure exacerbated liver injury, as evidenced by significant steatosis, inflammatory infiltration, fibrosis, and elevated serum ALT\/AST levels. It impaired intestinal barrier integrity and induced gut microbiota dysbiosis, characterized by altered microbial richness and differential abundance of specific bacteria. Liver metabolomics revealed significant perturbations, with the riboflavin metabolism pathway being the most notably enriched. Key metabolites in this pathway, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) showed dose-dependent alterations. Correlation analysis underscored a strong link between specific gut microbes and riboflavin metabolism intermediates. Network toxicology identified six hub targets\u2014IL-6, IL-1\u03b2, Casp3, Ppar\u03b3, Alb, and Tgf\u03b21 within the riboflavin metabolism network, and molecular docking confirmed their strong binding affinities with FMN and FAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrated that combined exposure to SiNP and HFD induced gut\u2013liver axis dysfunction and exacerbated MAFLD progression, which was mainly attributed to gut microbiota dysbiosis-mediated disruption of riboflavin metabolism. Our study highlighted the gut microbiota-riboflavin axis as a potentially promising intervention strategy for MAFLD, and identifies possible targets for the prevention and treatment of MAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1810542","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:19Z","timestamp":1778219719000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined exposure to silica nanoparticles and high-fat diet modulates metabolism-associated fatty liver disease via the gut\u2013liver axis"],"prefix":"10.3389","volume":"17","author":[{"given":"XueYan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health, Shandong Medical and Pharmaceutical University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, North China University of Science and Technology","place":["Tangshan, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong Medical and Pharmaceutical University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong Medical and Pharmaceutical University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, North China University of Science and Technology","place":["Tangshan, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, North China University of Science and Technology","place":["Tangshan, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenghong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shandong Medical and Pharmaceutical University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"102569","DOI":"10.1016\/j.redox.2022.102569","article-title":"Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress","volume":"59","author":"Abulikemu","year":"2023","journal-title":"Redox Biol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"130582","DOI":"10.1016\/j.bbagen.2024.130582","article-title":"Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity","volume":"1868","author":"Akasov","year":"2024","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1159\/000444066","article-title":"Physiological role of gut microbiota for maintaining human health","volume":"93","author":"Andoh","year":"2016","journal-title":"Digestion"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1002\/jimd.12058","article-title":"Disorders of riboflavin metabolism","volume":"42","author":"Balasubramaniam","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1080\/10408398.2023.2272269","article-title":"Targeting gut-liver axis by dietary lignans ameliorate obesity: evidences and mechanisms","volume":"65","author":"Chu","year":"2025","journal-title":"Crit. Rev. Food Sci. 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Sci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12989-024-00579-5","article-title":"Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p\/HO-1 signaling","volume":"21","author":"Li","year":"2024","journal-title":"Part. Fibre Toxicol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"117580","DOI":"10.1016\/j.ecoenv.2024.117580","article-title":"Effects of orally exposed SiO2 nanoparticles on lipid profiles in gut-liver axis of mice","volume":"290","author":"Li","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1080\/27697061.2025.2509900","article-title":"Exploring the epidemiology and molecular mechanisms of riboflavin against chronic kidney disease based on data mining, single-cell RNA sequencing and molecular docking","volume":"44","author":"Liu","year":"2025","journal-title":"J. Am. Nutr. Assoc."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1111\/codi.13400","article-title":"The use of Masson's trichrome staining, second harmonic imaging and two-photon excited fluorescence of collagen in distinguishing intestinal tuberculosis from Crohn's disease","volume":"18","author":"Mao","year":"2016","journal-title":"Color. Dis."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1017\/S0029665120006916","article-title":"SCFA: mechanisms and functional importance in the gut","volume":"80","author":"Martin-Gallausiaux","year":"2021","journal-title":"Proc. Nutr. Soc."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/hep4.1691","article-title":"Flavin adenine dinucleotide depletion caused by electron transfer flavoprotein subunit alpha haploinsufficiency leads to hepatic steatosis and injury in zebrafish","volume":"5","author":"Park","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"20420188221145549","DOI":"10.1177\/20420188221145549","article-title":"MAFLD: a multisystem disease","volume":"14","author":"Pipitone","year":"2023","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1927633","article-title":"Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis","volume":"13","author":"Rao","year":"2021","journal-title":"Gut Microbes"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"6753","DOI":"10.1038\/s41467-022-34275-9","article-title":"Deep learning-based image analysis predicts PD-L1 status from H&E-stained histopathology images in breast cancer","volume":"13","author":"Shamai","year":"2022","journal-title":"Nat. Commun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s11356-022-22179-6","article-title":"Changes in the liver proteome in apoE knockout mice exposed to inhalation of silica nanoparticles indicate mitochondrial damage and impairment of ER stress responses associated with microvesicular steatosis","volume":"30","author":"Stachyra","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"111496","DOI":"10.1016\/j.ecoenv.2020.111496","article-title":"Metabolomic characteristics of hepatotoxicity in rats induced by silica nanoparticles","volume":"208","author":"Sun","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"950","DOI":"10.3390\/ijms21030950","article-title":"Riboflavin: the health benefits of a forgotten natural vitamin","volume":"21","author":"Suwannasom","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"114920","DOI":"10.1016\/j.biopha.2023.114920","article-title":"Ginsenoside Rg1 ameliorates hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and inflammation by regulating CCN1","volume":"164","author":"Tang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"3650","DOI":"10.1080\/10408398.2016.1145104","article-title":"Riboflavin and health: a review of recent human research","volume":"57","author":"Thakur","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"4505","DOI":"10.3390\/nu14214505","article-title":"Dietary quality and relationships with metabolic dysfunction-associated fatty liver disease (MAFLD) among United States adults, results from NHANES 2017-2018","volume":"14","author":"Tian","year":"2022","journal-title":"Nutrients"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.freeradbiomed.2022.02.027","article-title":"Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS\/NLRP3\/Caspase-1 pathway","volume":"182","author":"Wang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"13700","DOI":"10.1021\/acs.jafc.4c01598","article-title":"Tomato pectin ameliorated hepatic steatosis in high-fat-diet mice by modulating gut microbiota and bile acid metabolism","volume":"72","author":"Wang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1007\/s12072-021-10138-1","article-title":"Gut-liver axis modulation of Panax notoginseng saponins in nonalcoholic fatty liver disease","volume":"15","author":"Xu","year":"2021","journal-title":"Hepatol. Int."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"7884","DOI":"10.1021\/acs.jafc.1c02257","article-title":"Oleanolic acid targets the gut-liver axis to alleviate metabolic disorders and hepatic steatosis","volume":"69","author":"Xue","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e13718","DOI":"10.1111\/acel.13718","article-title":"Riboflavin depletion promotes longevity and metabolic hormesis in Caenorhabditis elegans","volume":"21","author":"Yerevanian","year":"2022","journal-title":"Aging Cell"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"107694","DOI":"10.1016\/j.phrs.2025.107694","article-title":"Probiotics for the treatment of hyperlipidemia: focus on gut-liver axis and lipid metabolism","volume":"214","author":"You","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1111\/1751-7915.13410","article-title":"Akkermansia muciniphila is a promising probiotic","volume":"12","author":"Zhang","year":"2019","journal-title":"Microb. 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