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Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice
Abstract
The microbiota-gut-brain axis (MGBA) regulates the reciprocal interaction between chronic inflammatory bowel and psychiatric disorders. This interaction involves multiple pathways that are highly debated. We examined the behavioural, biochemical and electrophysiological alterations, as well as gut microbiota composition in a model of antibiotic-induced experimental dysbiosis. Inflammation of the small intestine was also assessed. Mice were exposed to a mixture of antimicrobials for 2weeks. Afterwards, they received Lactobacillus casei DG (LCDG) or a vehicle for up to 7days via oral gavage. Perturbation of microbiota was accompanied by a general inflammatory state and alteration of some endocannabinoidome members in the gut. Behavioural changes, including increased immobility in the tail suspension test and reduced social recognition were observed, and were associated with altered BDNF/TrkB signalling, TRPV1 phosphorylation and neuronal firing in the hippocampus. Moreover, morphological rearrangements of non-neuronal cells in brain areas controlling emotional behaviour were detected. Subsequent probiotic administration, compared with vehicle, counteracted most of these gut inflammatory, behavioural, biochemical and functional alterations. Interestingly, levels of Lachnospiraceae were found to significantly correlate with the behavioural changes observed in dysbiotic mice. Our findings clarify some of the biomolecular and functional modifications leading to the development of affective disorders associated with gut microbiota alterations.
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“antibiotic administration to laboratory animals has been shown to influence behaviors such as sociability and anxiety (Degroote et al., 2016;Frohlich et al., 2016;Guida et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Guida et al., 2018
In the citing paper
“This was somewhat ameliorated by treatment with the probiotic L. casei DG probably via a gut anti-inflammatory mechanism (Guida et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Guida et al., 2018
In the citing paper
“two weeks of antibiotic cocktail administration resulted in marked changes in hippocampal BDNF tropomyosin receptor kinase B (TrkB) signaling, transient receptor potential vanilloid 1 (TRPV1) phosphorylation and overall heavily reduced hippocampal CA3-CA1 synaptic activity.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Guida et al., 2018
In the citing paper
“antibiotic-induced ablation of the gut microbiota in rodents results in long-term effects on neurochemistry and behavior (Champagne-Jorgensen et al., 2019;Desbonnet et al., 2015;Guida et al., 2018;Neufeld et al., 2011)”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Guida et al., 2018
In the citing paper
“While the linkage between Muribaculaceae and neurophysiology has been less well documented relative to other mouse microbiome taxa, prior work has associated the relative abundance of ASVs from this group to various measures of mouse cognition48,56.”
From Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice (2021) · cites this paper as [56]
In the citing paper
“the findings showing that antibiotics may be related to depression [159,168].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [159]
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Metadata
- Authors
- Guida, F., Turco, F., Iannotta, M., De Gregorio, D., Palumbo, I., Sarnelli, G., Furiano, A., Napolitano, F., Boccella, S., Luongo, L., Mazzitelli, M., Usiello, A., De Filippis, F., Iannotti, F. A., Piscitelli, F., Ercolini, D., de Novellis, V., Di Marzo, V., Cuomo, R., & Maione, S.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Federico II University Hospital (IT)
- CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT)
- Istituto di Chimica Biomolecolare (IT)
- University of Naples Federico II (IT)
- Corresponding author
- Guida, F.
- Maione, S.
- ORCID
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 67
- Pages
- 230-245
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2753690838
- Cited by
- 367
- References
- 87
- Citations by year
- 2026: 20 · 2025: 45 · 2024: 52 · 2023: 58 · 2022: 49 · 2021: 48 · 2020: 38 · 2019: 37 · 2018: 18
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- 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
- microbiota-gut-brain axis, antibiotic-induced dysbiosis, depression, probiotics, Lactobacillus casei, BDNF/TrkB signaling, TRPV1, Lachnospiraceae, intestinal inflammation, social recognition, anxiety-like behavior, mood disorders
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Bacterial Agents, Behavior, Animal, Depression, Hippocampus, Inflammation, Intestinal Mucosa, Intestines, Male, Mice, Inbred C57BL, Neuroglia, Neurons, Brain-Derived Neurotrophic Factor, Probiotics, Endocannabinoids, Dysbiosis
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