{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:09:29Z","timestamp":1788772169829,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010814","name":"Scientific Research Foundation of the Education Department of Anhui Province of China","doi-asserted-by":"publisher","award":["2023AH052198"],"award-info":[{"award-number":["2023AH052198"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Early-life antibiotic exposure is a critical environmental trigger for developmental metabolic disorders and long-term obesity risk. Lactational enrofloxacin exposure exerts potential metabolic programming toxicity, but its long-term effects and underlying mechanisms remain poorly defined. This study aimed to investigate the persistent influences of lactational enrofloxacin exposure on postnatal growth, lipid metabolism and adipogenesis in mouse offspring and explore the potential gut microbiota-associated regulatory mechanism. A combined in vivo and in vitro approach was utilized. In vivo mouse models with lactational enrofloxacin exposure were established to assess growth phenotypes, serum lipid profiles, adipose morphology, and gut microbial composition via high-throughput sequencing. Antibiotic cocktail treatment was performed to deplete gut microbiota. In vitro 3T3-L1 cell models and pharmacological inhibition assays were used to investigate the downstream signaling pathway. Lactational enrofloxacin exposure was associated with disrupted postnatal growth, persistent weight gain, fat accumulation and progressive dyslipidemia in offspring. Adipose expansion was mainly attributed to adipocyte hyperplasia. It triggered sustained gut dysbiosis, increased Gram-negative Proteobacteria, and elevated circulating lipopolysaccharide (LPS) levels (systemic endotoxemia). Microbiota depletion largely reversed these metabolic abnormalities. In vitro, LPS facilitated preadipocyte differentiation and lipid deposition, consistent with activation of a PPAR\u03b3-dependent mechanism (putatively via TLR4). Our findings suggest that lactational enrofloxacin exposure is associated with persistent fat accumulation and lipid metabolism disorders in offspring and support a key role for the gut microbiota\u2013LPS\u2013PPAR\u03b3 signaling pathway, with TLR4 as the putative upstream receptor, in this process. These findings provide insights into the developmental metabolic toxicity of early-life fluoroquinolone exposure and offer a theoretical basis for preventing early-onset metabolic diseases.<\/jats:p>","DOI":"10.3390\/microorganisms14091964","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactational Enrofloxacin Exposure Promotes Offspring Lipid Metabolic Disorder and Adiposity Involving Gut Microbiota-Derived LPS and PPAR\u03b3 Signaling"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuhui","family":"Li","sequence":"first","affiliation":[{"name":"School of Life and Health Sciences, Environmental Engineering, Hefei University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Yating","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Environmental Engineering, Hefei University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Zhongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Environmental Engineering, Hefei University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Environmental Engineering, Hefei University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Anqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Environmental Engineering, Hefei University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Jigang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Environmental Engineering, Hefei University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6381-6440","authenticated-orcid":false,"given":"Yehao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s40519-026-01820-0","article-title":"Obesity is always a clinically relevant chronic disease","volume":"31","author":"Donini","year":"2026","journal-title":"Eat. 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