Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice
Open accessAbstract
The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1+), monocytes (CD11b+/CD45+), and dendritic cells (CD11b+/CD11c+) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3+/NeuN+) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1β and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.
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Antibiotic-induced perturbations in gut microbial diversity influence neuroinflammation with altered microglial morphology.
“antibiotic-induced perturbations in gut microbial diversity influence neuroinflammation with altered microglial morphology (105–107).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [107]
The Results report that ampicillin changed gut microbial composition, and the Discussion links ampicillin-associated changes to microglial recruitment and neuroinflammation in mice (page numbers unavailable). The paper does not report altered microglial morphology; it measures or describes microglial cells and their recruitment instead. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPerturbations in microbial diversity due to antimicrobials influence pro-inflammatory cytokine secretion in the CNS and alter microglial morphology.
“Perturbations in microbial diversity, secondary to antimicrobials, have been shown to influence pro-inflammatory cytokine secretion in the CNS and alter microglial morphology (268–270).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [270]
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- Authors
- Jang, H.-M., Lee, H.-J., Jang, S.-E., Han, M. J., & Kim, D.-H.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Kim, Dong-Hyun
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 11
- Issue
- 5
- Pages
- 1386-1397
- ISSN
- 1933-0219 (ISSN-L)
- OpenAlex
- W2806345334
- Cited by
- 181
- References
- 54
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 22 · 2023: 34 · 2022: 29 · 2021: 38 · 2020: 22 · 2019: 11 · 2018: 2
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea (NRF-2017R1A5A2014768, 2017R1A5A2014768)
- Ministry of Science and ICT, South Korea (NRF-2017R1A5A2014768, 2017R1A5A2014768)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, anxiety, neuroinflammation, ampicillin, Klebsiella oxytoca, Proteobacteria, Lactobacillus reuteri, lipopolysaccharide, colitis, gut-brain axis, microglia, monocytes, dendritic cells, hippocampus, corticosterone, interleukin-6, NF-κB, IL-1β, TNF-α, intestinal permeability, antibiotic-induced dysbiosis
- MeSH terms
- Gastrointestinal Microbiome, Ampicillin, Animals, Anti-Bacterial Agents, Anxiety, Colon, Corticosterone, Dendritic Cells, Feces, Hippocampus, Inflammation, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Monocytes, Neurons, Interleukin-6, Microglia, Proteobacteria, Mice
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