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Prenatal exposure to low-dose ciprofloxacin antibiotic increased male offspring's defensive aggressive behaviors via a gut-phosphatidylcholine-α7 nAChR axis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Prenatal exposure to low-dose ciprofloxacin antibiotic increased male offspring's defensive aggressive behaviors via a gut-phosphatidylcholine-α7 nAChR axis.
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
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  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Prenatal+Exposure+Delayed+Effects%22&quot;&gt;Prenatal Exposure Delayed Effects*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Prenatal+Exposure+Delayed+Effects+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Ciprofloxacin%22&quot;&gt;Ciprofloxacin*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Ciprofloxacin+pharmacology%22&quot;&gt;pharmacology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Ciprofloxacin%22&quot;&gt;Ciprofloxacin*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Ciprofloxacin+adverse+effects%22&quot;&gt;adverse effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Ciprofloxacin%22&quot;&gt;Ciprofloxacin*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Ciprofloxacin+administration+%26+dosage%22&quot;&gt;administration &amp; dosage&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Phosphatidylcholines%22&quot;&gt;Phosphatidylcholines*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Phosphatidylcholines+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Anti-Bacterial+Agents%22&quot;&gt;Anti-Bacterial Agents*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Anti-Bacterial+Agents+pharmacology%22&quot;&gt;pharmacology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Anti-Bacterial+Agents%22&quot;&gt;Anti-Bacterial Agents*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Anti-Bacterial+Agents+adverse+effects%22&quot;&gt;adverse effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Aggression%22&quot;&gt;Aggression*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Aggression+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Aggression%22&quot;&gt;Aggression*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Aggression+physiology%22&quot;&gt;physiology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22alpha7+Nicotinic+Acetylcholine+Receptor%22&quot;&gt;alpha7 Nicotinic Acetylcholine Receptor*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22alpha7+Nicotinic+Acetylcholine+Receptor+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Gastrointestinal+Microbiome%22&quot;&gt;Gastrointestinal Microbiome&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Gastrointestinal+Microbiome+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus%22&quot;&gt;Hippocampus&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus%22&quot;&gt;Hippocampus&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Behavior%2C+Animal%22&quot;&gt;Behavior, Animal&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Behavior%2C+Animal+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Animals%22&quot;&gt;Animals&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Pregnancy%22&quot;&gt;Pregnancy&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Male%22&quot;&gt;Male&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Female%22&quot;&gt;Female&lt;/searchLink&gt;
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  Group: Ab
  Data: 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.&lt;br /&gt; (Copyright &#169; 2026 Elsevier Inc. All rights reserved.)
– Name: Abstract
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  Data: 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.
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  Data: &lt;i&gt;Keywords: &lt;/i&gt;Defensive aggression; Gut–brain axis; Lactobacillus reuteri; Neuroinflammation; Phosphatidylcholine; Prenatal ciprofloxacin exposure
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  Data: 5E8K9I0O4U (Ciprofloxacin)&lt;br /&gt;0 (Phosphatidylcholines)&lt;br /&gt;0 (Anti-Bacterial Agents)&lt;br /&gt;0 (alpha7 Nicotinic Acetylcholine Receptor)
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          Name:
            NameFull: Ren T
      – PersonEntity:
          Name:
            NameFull: Lin J
      – PersonEntity:
          Name:
            NameFull: Liu X
      – PersonEntity:
          Name:
            NameFull: Shi H
      – PersonEntity:
          Name:
            NameFull: Cai N
      – PersonEntity:
          Name:
            NameFull: Yu X
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 08
              Text: 2026 Aug
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1090-2139
          Numbering:
            – Type: volume
              Value: 136
          Titles:
            – TitleFull: Brain, behavior, and immunity
              Type: main
ResultId 1