Evidence map›Paper›PMID 41724956›Full record

ArticleCellular & molecular biology letters2026

Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.

Yuhao Xu, Lili Huang, Liang Sun, Chenggang Li, Chao Zhou, Pinyi Liu, Zhi Zhang, Shiji Deng, Chenglu Mao, Zheqi Hu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular biology letters, 2026. 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. Review
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

13 authors.

Yuhao Xu *Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Lili Huang *Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Liang SunDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Chenggang LiDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Chao ZhouDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Pinyi LiuDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Zhi ZhangDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Shiji DengDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Chenglu MaoDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Zheqi HuDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Xinyu BaoDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Shengnan XiaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Yun XuDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China. xuyun208@163.com.

Funding

Jiangsu Province Key Medical Discipline ZDXK202216National Natural Science Foundation of China 82130036/823B2027STI2030-Major Projects 2022ZD0211800
6 · The paper itself

Abstract

backgroundWhite matter injury (WMI) is the most prevalent lesion in cerebral small vessel disease and a major contributor to cognitive decline. Recent studies have highlighted the critical role of gut microbiota in regulating brain disorders. However, the role of gut microbiota in WMI-related cognitive decline remains unclear.

methodsA bilateral carotid artery stenosis (BCAS) mouse model was established to mimic WMI and related cognitive decline. Fecal microbiota transplantation was employed to verify the causal relationship between gut microbiota dysbiosis and WMI. 16 S rRNA gene sequencing was used to analyze gut microbiota and its potential functions. Untargeted metabolomics was applied to identify differential metabolites. Cognitive function was assessed through Y-maze, novel object recognition, and fear conditioning tests. WMI was assessed using in vivo imaging, immunostaining, and electron microscopy. The changes in oligodendrocyte lineage cells, microglia, and blood-brain barrier were investigated using immunofluorescence staining, EdU cell proliferation assays, and Western blotting. Patients with ischemic WMI were included to examine the correlation between serum L-arginine (L-Arg) levels, brain imaging, and cognition.

resultsWe discovered that BCAS mice exhibited gut microbiota dysbiosis and reduced arginine biosynthesis, with decreased L-Arg levels in serum and white matter. Fecal microbiota from BCAS mice resulted in WMI and related cognitive decline in normal mice. Serum L-Arg levels were reduced in patients with ischemic WMI and were closely associated with WMI and cognitive decline. Importantly, L-Arg supplementation improved WMI-related cognitive decline in BCAS mice. Mechanistically, L-Arg promoted oligodendrocyte precursor cell proliferation and differentiation, enhanced the anti-inflammatory activity of microglia, and reduced blood-brain barrier leakage, thereby mitigating WMI-related cognitive decline. Furthermore, Lachnospiraceae was identified as the main source of gut-to-brain L-Arg. Supplementation with Lachnospiraceae alleviates WMI-related cognitive decline.

conclusionOverall, our study revealed the critical role of gut microbiota, particularly Lachnospiraceae, and L-Arg in improving WMI-related cognitive decline, providing novel strategies for understanding and treating WMI-related cognitive decline.

Indexed as

ArginineCognitive DysfunctionGastrointestinal MicrobiomeWhite MatterAnimalsDisease Models, AnimalDysbiosisFecal Microbiota TransplantationHumansMaleMiceMice, Inbred C57BLMicrogliaOligodendrogliaArginineCognitive declineGut microbiotaLachnospiraceaeL-arginineWhite matter injury

Identifiers

PMID41724956
PMCPMC13032417

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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.