Dysbiosis of Gut Microbiota and Short-Chain Fatty Acids in Encephalitis: A Chinese Pilot Study

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Reviewed Marked as Reviewed by Svetlana up on 2024-12-13
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Xu R, Tan C, He Y, Wu Q, Wang H, Yin J
Journal
Frontiers in immunology
Year
2020
Keywords:
dysbiosis, encephalitis, gut microbiome, intestinal barrier, short-chain fatty acids
BACKGROUND: Encephalitis, the inflammation of the brain, may be caused by an infection or an autoimmune reaction. However, few researches were focused on the gut microbiome characteristics in encephalitis patients. METHODS: A prospective observational study was conducted in an academic hospital in Guangzhou from February 2017 to February 2018. Patients with encephalitis were recruited. Fecal and serum samples were collected at admission. Healthy volunteers were enrolled from a community. Disease severity scores were recorded by specialized physicians, including Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation-II (APACHE-II). 16S rRNA sequence was performed to analyze the gut microbiome, then the α-diversities and β-diversities were estimated. Short-chain fatty acids (SCFAs) were extracted from fecal samples and determined by gas chromatography-mass spectrometry. Serum D-lactate (D-LA), intestinal fatty acid-binding protein (iFABP), lipopolysaccharide (LPS), and lipopolysaccharide-binding protein (LBP) were measured by enzyme-linked immunosorbent assay (ELISA). The associations among microbial indexes and clinical parameters were evaluated by Spearman correlation analysis. RESULTS: In total, twenty-eight patients were recruited for analysis (median age 46 years; 82.1% male; median GCS 6.5; median SOFA 6.5; median APACHE-II 14.5). Twenty-eight age- and sex-matched healthy subjects were selected as controls. The β-diversities between patients and healthy subjects were significantly different. The α-diversities did not show significant differences between these two groups. In the patient group, the abundances of Bacteroidetes, Proteobacteria, and Bacilli were significantly enriched. Accordingly, fecal SCFA levels were decreased in the patient group, whereas serum D-LA, iFABP, LPS, and LBP levels were increased compared with those in healthy subjects. Correlation analyses showed that disease severity had positive correlations with Proteobacteria and Akkermansia but negative correlations with Firmicutes, Clostridia, and Ruminococcaceae abundances. The cerebrospinal fluid albumin-to-serum albumin ratio (CSAR) was positively related to the α-diversity but negatively correlated with the fecal butyrate concentration. CONCLUSION: Gut microbiota disruption was observed in encephalitis patients, which manifested as pathogen dominance and health-promoting commensal depletion. Disease severity and brain damage may have associations with the gut microbiota or its metabolites. The causal relationship should be further explored in future studies.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-12-13

Curated date: 2024/10/16

Curator: Rahila

Revision editor(s): Rahila, Aleru Divine, Svetlana up

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
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
Encephalitis brain inflammation,Encephalitis,encephalitis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls (CON)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Encephalitis (ENC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who suffered from brain inflammation (encephalitis)
Group 0 sample size Number of subjects in the control (unexposed) group
28
Group 1 sample size Number of subjects in the case (exposed) group
28
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
12 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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
3.5
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

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
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-13

Curated date: 2024/10/16

Curator: Rahila

Revision editor(s): Rahila, Aleru Divine

Source: FIG 1 (G)

Description: Cladogram based on LEfSe results of the encephalitis patients (ENC) and healthy subjects serving as controls (CON).

Abundance in Group 1: increased abundance in Encephalitis (ENC)

NCBI Quality ControlLinks
Bacilli
Christensenellaceae
Chroococcales
Enterobacteriaceae
Enterococcaceae
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Gammaproteobacteria
Lactobacillales
Oscillatoriophycideae
Porphyromonadaceae
Pseudomonadales
Rikenellaceae
Verrucomicrobiaceae
Verrucomicrobiales
Verrucomicrobiia
Xenococcaceae
Enterobacterales

Revision editor(s): Rahila, Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-13

Curated date: 2024/10/16

Curator: Rahila

Revision editor(s): Rahila

Source: FIG 1 (G)

Description: Cladogram based on LEfSe results of the encephalitis patients (ENC) and healthy subjects serving as controls (CON).

Abundance in Group 1: decreased abundance in Encephalitis (ENC)

NCBI Quality ControlLinks
Prevotellaceae
Clostridiaceae
Lachnospiraceae
Veillonellaceae
Alcaligenaceae
Burkholderiales
Betaproteobacteria

Revision editor(s): Rahila

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-12-13

Curated date: 2024/10/17

Curator: Rahila

Revision editor(s): Rahila, Aleru Divine

Differences from previous experiment shown

Subjects

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Antibiotics use in the last year prior to sample collection.

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

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
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-13

Curated date: 2024/10/17

Curator: Rahila

Revision editor(s): Rahila, Aleru Divine

Source: Table 2.

Description: Significantly discriminative taxa between the twenty-eight Encephalitis patients and healthy subjects determined by Mann-Whitney U tests.

Abundance in Group 1: increased abundance in Encephalitis (ENC)

NCBI Quality ControlLinks
Bacilli
Enterobacterales
Enterobacteriaceae
Erysipelotrichales
Gammaproteobacteria
Lactobacillales
Muribaculaceae
Oscillospira
Parabacteroides
Porphyromonadaceae
Pseudomonadota
Rikenellaceae

Revision editor(s): Rahila, Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-13

Curated date: 2024/10/17

Curator: Rahila

Revision editor(s): Rahila, Aleru Divine

Source: Table 2.

Description: Significantly discriminative taxa between the twenty-eight Encephalitis patients and healthy subjects determined by Mann-Whitney U tests.

Abundance in Group 1: decreased abundance in Encephalitis (ENC)

NCBI Quality ControlLinks
Betaproteobacteria
Burkholderiales
Faecalibacterium
Lachnospiraceae
Prevotella
Ruminococcus
Sutterella

Revision editor(s): Rahila, Aleru Divine