Evidence map›Paper›PMID 40222582›Full record

ArticleThe Journal of nutrition2025

Clostridioides difficile Infection in Aged Mice Decreases Memory Function, Which Can Be Protected with Alanyl-Glutamine Supplementation.

Sophia M Goldbeck, Deiziane Vs Costa, Suemin E Yang, Caroline C Whitt, Ayesha E Tora, Cirle A Warren, Jae Hyun Shin

Abstract read
In one paragraph

Article in The Journal of nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Sophia M GoldbeckUniversity of North Carolina School of Medicine, Chapel Hill, NC, United States; Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States.
Deiziane Vs CostaDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States.
Suemin E YangDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States.
Caroline C WhittDepartment of Physical and Rehabilitation Medicine, University of Virginia, Charlottesville, VA, United States; Hoag Memorial Hospital Presbyterian, Newport Beach, CA, United States.
Ayesha E ToraDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States.
Cirle A WarrenDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States. Electronic address: ca6t@virginia.edu.
Jae Hyun ShinDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States; Hoag Memorial Hospital Presbyterian, Newport Beach, CA, United States.

Funding

Alanyl-glutamine supplementation of standard treatment for C. difficile infectionR01AI145322 · NIAID · UNIVERSITY OF VIRGINIA · PI WARREN, CIRLE ALCANTARA · 2020 to 2024
$4.0M
Aging and Clostridium difficile infection: interplay of microbiota and host responseK08AG064151 · NIA · UNIVERSITY OF VIRGINIA · PI SHIN, JAE HYUN · 2019 to 2023
$801k
NIAID NIH HHS R01 AI145322NIA NIH HHS K08 AG064151
6 · The paper itself

Abstract

backgroundAdults aged >65 face a higher risk of both Clostridioides difficile infection (CDI) and dementia. CDI in the elderly may exacerbate functional and cognitive impairments. Current CDI treatment options are limited. Alanyl-glutamine (AQ) is a dipeptide shown to decrease C. difficile toxin effects in vitro and in vivo.

objectivesWe tested the potential benefits of AQ on the clinical outcomes and cognitive impairment in the aged mouse model of CDI treated at various timings of AQ and vancomycin treatment.

methodsC57BL/6 retired breeder (9 mo) and aged (18 mo) mice were treated with AQ-supplemented water as a 2-wk pretreatment or continuously. The mice underwent a standard CDI protocol (VPI10463) and were treated, or not, with vancomycin. Disease severity was tracked for 14 d, then novel object recognition (NOR) tests for acute memory were performed. Hippocampal tissues were assayed for molecular markers.

resultsNOR testing confirmed CDI-induced cognitive impairment (P = 0.0352). AQ pretreatment had mild neuroprotective effects during CDI. Mice treated with vancomycin and continuous AQ had better clinical scores and better memory performance than vancomycin controls (P = 0.0286). Continuous AQ treatment, when used alone or paired with vancomycin, offered protection against CDI-induced cognitive impairment. The mechanism of CDI-induced memory impairment remains unclear, but infected mice had elevated synaptobrevin-2 (P = 0.0396) and neural cell adhesion molecule (P = 0.008) compared with uninfected controls on day 14 post infection.

conclusionsOur findings suggest that neuroinflammation and memory loss occur during CDI, which may be ameliorated by AQ supplementation. AQ supplementation may have both neurological and intestinal protective effects during CDI treatment.

Indexed as

AgingClostridioides difficileClostridium InfectionsDietary SupplementsDipeptidesMemoryMemory DisordersAnimalsAnti-Bacterial AgentsDisease Models, AnimalHippocampusMaleMiceMice, Inbred C57BLVancomycinalanylglutamineAnti-Bacterial AgentsDipeptidesVancomycinAlanyl-glutamineClostridioides difficilecognitiondementiagut–brain axis

Identifiers

PMID40222582
PMCPMC12612603

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.