Cingulate white matter mediates the effects of fecal Ruminococcus on neuropsychiatric symptoms in patients with amyloid-positive amnestic mild cognitive impairment

Study information

Reviewed Marked as Reviewed by KateRasheed on 2025-5-9

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

37936084

DOI Digital object identifier for electronic documents.

10.1186/s12877-023-04417-9

URI Uniform resource identifier for web resources.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11055349/

Authors

Hung CC, Chao YP, Lee Y, Huang CW, Huang SH, Chang CC, Cheng CH

Journal

BMC geriatrics

Year

2023

Keywords:

Amnestic mild cognitive impairment, Diffusion tensor imaging, Gut microbiota, Limbic system, Neuropsychiatric symptoms, Ruminococcus

BACKGROUND: Microbiota-gut-brain axis interacts with one another to regulate brain functions. However, whether the impacts of gut dysbiosis on limbic white matter (WM) tracts contribute to the neuropsychiatric symptoms (NPS) in patients with amyloid-positive amnestic mild cognitive impairment (aMCI+), have not been explored yet. This study aimed to investigate the mediation effects of limbic WM integrity on the association between gut microbiota and NPS in patients with aMCI+. METHODS: Twenty patients with aMCI + and 20 healthy controls (HCs) were enrolled. All subjects underwent neuropsychological assessments and their microbial compositions were characterized using 16S rRNA Miseq sequencing technique. Amyloid deposition inspected by positron emission tomography imaging and limbic WM tracts (i.e., fornix, cingulum, and uncinate fasciculus) detected by diffusion tensor imaging were additionally measured in patients with aMCI+. We employed a regression-based mediation analysis using Hayes's PROCESS macro in this study. RESULTS: The relative abundance of genera Ruminococcus and Lactococcus was significantly decreased in patients with aMCI + versus HCs. The relative abundance of Ruminococcus was negatively correlated with affective symptom cluster in the aMCI + group. Notably, this association was mediated by WM integrity of the left cingulate gyrus. CONCLUSIONS: Our findings suggest Ruminococcus as a potential target for the management of affective impairments in patients with aMCI+.

Experiment 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-5-9

Curated date: 2025/04/26

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Subjects

Location of subjects: Taiwan

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: Cognitive impairment measurement Cognitive impairment measurement,cognitive impairment measurement

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy control (HC).

Group 1 name Corresponds to the case (exposed) group for case-control studies: Amnestic mild cognitive impairment (aMCI+).

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with amnestic mild cognitive impairment "Amyloid positive" (aMCI+).

Group 0 sample size Number of subjects in the control (unexposed) group: 20

Group 1 sample size Number of subjects in the case (exposed) group: 20

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 2 Months

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: Mann-Whitney (Wilcoxon)

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

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

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-5-9

Curated date: 2025/04/26

Curator: Shulamite

Revision editor(s): Shulamite

Source: Fig 1A

Description: Mann-Whitney U test revealed significantly differential abundance of genera Ruminococcus and Lactococcus between aMCI + and HC groups.

Abundance in Group 1: decreased abundance in Amnestic mild cognitive impairment (aMCI+).

NCBI	Quality Control	Links
Lactococcus
Ruminococcus

Revision editor(s): Shulamite

Experiment 2

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Curated date: 2025/04/26

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

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): 2 Months.

Statistical Analysis

Statistical test: LEfSe

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

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

Signature 1

Edit History Delete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by KateRasheed on 2025-5-9

Curated date: 2025/04/26

Curator: Shulamite

Revision editor(s): Shulamite

Source: Fig 1B

Description: LEfSe analysis showed significantly differential abundance of genera Ruminococcus and Lactococcus between aMCI+ (positive scores) and HC (negative scores) groups.

Abundance in Group 1: decreased abundance in Amnestic mild cognitive impairment (aMCI+).

NCBI	Quality Control	Links
Lactococcus
Ruminococcus

Revision editor(s): Shulamite