Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Chen A, Teng C, Wei J, Wu X, Zhang H, Chen P, Cai D, Qian H, Zhu H, Zheng X, Chen X
Journal
Gut microbes
Year
2025
Keywords:
Neonatal hypoxic-ischemic brain damage, cognitive impairments, fecal microbiota transplantation, microbiota-gut-brain axis, neuroinflammation
Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.
Experiment 1
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Rattus norvegicus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Brain hypoxia-Ischemia Hypoxia-Ischemia, Brain,Brain hypoxia-Ischemia,brain hypoxia-Ischemia
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Sham Group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HI Goup
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Neonatal rats that underwent hypoxia-ischema (HI) to induce brain injury
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 2h, 2i, 2j, 2k, 2m
Description: Taxonomic differences in gut microbiota between rats in SHAM group and HI group.
Abundance in Group 1: increased abundance in HI Goup
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| Fusobacteriaceae | ||
| Prevotellaceae | ||
| Pseudomonadota | ||
| Streptococcaceae | ||
| Vibrionaceae |
Revision editor(s): IsaacImitini
Signature 2
Needs review
Source: Figure 2h, 2i, 2j 2k,2m
Description: Taxonomic differences in gut microbiota between rats in SHAM group and HI group.
Abundance in Group 1: decreased abundance in HI Goup
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansiaceae | ||
| Bacteroidota | ||
| Caryophanaceae | ||
| Enterococcaceae | ||
| Helicobacteraceae | ||
| Victivallaceae |
Revision editor(s): IsaacImitini
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Treatment Treatment,treatment
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HI group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HI + DEX group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Neonatal rats that underwent hypoxia-ischemia (HI) and received Dexamethasone (DEX) treatment.
Lab analysis
- Sequencing type
- PCR
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Not specified
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Statistical test
- Not specified
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Not specified
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Signature 1
Needs review
Source: Figure S3a & b
Description: Quantification of Enterobacteriaceae and Akkermansiaceae in the fecal samples.
Abundance in Group 1: increased abundance in HI + DEX group
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansiaceae |
Revision editor(s): IsaacImitini
Signature 2
Needs review
Source: Figure S3a & b
Description: Quantification of Enterobacteriaceae and Akkermansiaceae in the fecal samples.
Abundance in Group 1: decreased abundance in HI + DEX group
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae |
Revision editor(s): IsaacImitini
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