Academic Journal
Prenatal exposure to low-dose ciprofloxacin antibiotic increased male offspring's defensive aggressive behaviors via a gut-phosphatidylcholine-α7 nAChR axis.
| Τίτλος: | Prenatal exposure to low-dose ciprofloxacin antibiotic increased male offspring's defensive aggressive behaviors via a gut-phosphatidylcholine-α7 nAChR axis. |
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| Συγγραφείς: | Cao A; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Liu Y; Hebei Key Laboratory of Early Life Health Promotion (SZX202419), Hebei Medical University, Shijiazhuang, China; Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China., Qi D; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Li Z; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Du Y; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Xu Q; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Yue J; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Zheng L; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Wang Y; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Cui J; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Chen C; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Ren T; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Lin J; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China., Liu X; Hebei Key Laboratory of Early Life Health Promotion (SZX202419), Hebei Medical University, Shijiazhuang, China; Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China., Shi H; Hebei Key Laboratory of Early Life Health Promotion (SZX202419), Hebei Medical University, Shijiazhuang, China; Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, China. Electronic address: shihs@hebmu.edu.cn., Cai N; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China. Electronic address: cainning@hebmu.edu.cn., Yu X; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Early Life Health Promotion (SZX202419), Hebei Medical University, Shijiazhuang, China; Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China. Electronic address: yuxiaohui@hebmu.edu.cn. |
| Πηγή: | Brain, behavior, and immunity [Brain Behav Immun] 2026 Aug; Vol. 136, pp. 106572. Date of Electronic Publication: 2026 Mar 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2000- > : Amsterdam : Elsevier Original Publication: San Diego : Academic Press, [c1987- |
| Ιατρικοί όροι (MeSH): | Prenatal Exposure Delayed Effects*/metabolism , Ciprofloxacin*/pharmacology , Ciprofloxacin*/adverse effects , Ciprofloxacin*/administration & dosage , Phosphatidylcholines*/metabolism , Anti-Bacterial Agents*/pharmacology , Anti-Bacterial Agents*/adverse effects , Aggression*/drug effects , Aggression*/physiology , alpha7 Nicotinic Acetylcholine Receptor*/metabolism, Gastrointestinal Microbiome/drug effects ; Hippocampus/metabolism ; Hippocampus/drug effects ; Behavior, Animal/drug effects ; Animals ; Pregnancy ; Male ; Female |
| Περίληψη: | Prenatal adversities disrupt the development of the gut microbiota and thereby increase the risk of neuropsychiatric disorders in later life. However, the effects of prenatal antibiotic exposure on aggressive behavior in adulthood and the underlying gut-brain mechanisms remain poorly defined. Here, we showed that low-dose exposure to the fluoroquinolone ciprofloxacin during late gestation increased defensive aggressive behavior in adult male offspring. Prenatal ciprofloxacin exposure thinned the colonic mucus layer, reduced MUC2 secretion, and depleted mucosa-associated Lactobacillus species, thereby reshaping the microbial ecosystem and disturbing systemic phosphatidylcholine (PC) homeostasis. This microbiota-lipid dysregulation is accompanied by reduced hippocampal α7 nicotinic acetylcholine receptor (α7 nAChR) expression, increased microglial activation and a pro-inflammatory cytokine profile, as well as increased neuronal activity in the hippocampus. Correlation analyses further linked altered PC species to bacterial taxa, supporting a microbiota-associated PC-α7 nAChR axis in the regulation of defensive aggression. Importantly, post-weaning supplementation with either phosphatidylcholine or Lactobacillus reuteri (L. reuteri) attenuated defensive aggression in adult offspring prenatally exposed to ciprofloxacin. Altogether, these findings provide new insights into the gut-lipid-brain mechanisms by which prenatal antibiotics program aggressive behavior in adulthood and highlight phosphatidylcholine or L. reuteri supplementation as promising interventions for alleviating aggression abnormalities induced by prenatal antibiotic exposure. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Defensive aggression; Gut–brain axis; Lactobacillus reuteri; Neuroinflammation; Phosphatidylcholine; Prenatal ciprofloxacin exposure |
| Substance Nomenclature: | 5E8K9I0O4U (Ciprofloxacin) 0 (Phosphatidylcholines) 0 (Anti-Bacterial Agents) 0 (alpha7 Nicotinic Acetylcholine Receptor) |
| Entry Date(s): | Date Created: 20260329 Date Completed: 20260710 Latest Revision: 20260710 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.bbi.2026.106572 |
| PMID: | 41905488 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2139 |
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| DOI: | 10.1016/j.bbi.2026.106572 |