Evidence map›Paper›PMID 41042380›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025

Integrative genomics and functional immunology reveal Clostridia species as modulators of neuroinflammation in amyotrophic lateral sclerosis.

Shuyu Wang, Hongquan Jiang, Ting Yao

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Shuyu WangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Hongquan JiangDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China. quan@hrbmu.edu.cn.
Ting YaoDepartment of Pediatric Surgery, The Six Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China. tingyao_hyd@hotmail.com.ORCID http://orcid.org/0000-0001-8412-3793

Funding

Doctoral Fund of the First Affiliated Hospital of Harbin Medical University 2020B22Innovative Scientific Research Funding Project of Harbin Medical University 2022-KYYWF-0301Natural Science Foundation of Heilongjiang Province,China PL2024H140The key research and development project of Heilongjiang Province 2023ZX07D06
6 · The paper itself

Abstract

objectiveThis multiomics study investigated causal relationships between the gut microbiota (GM), immune dysregulation, and amyotrophic lateral sclerosis (ALS) pathogenesis using Mendelian randomization (MR) with experimental validation. MATERIALS: Analyses incorporated genome-wide data from 87,347 participants (GM: n = 7738; ALS: 20,806 patients, 59,804 controls; immune phenotypes: n = 3757), transcriptomic data from 71 subjects (56 ALS patients, 15 controls), and experimental validation in matched cohorts (n = 6 subjects per group).

methodsTwo-sample bidirectional MR and mediation analysis were used to evaluate associations. Experimental validation employed flow cytometry for myeloid-derived suppressor cell quantification, enzyme-linked immunosorbent assay for cytokines, and real-time polymerase chain reaction for bacterial validation. Statistical analyses included inverse variance weighted methods with Cohen's d calculations.

resultsSixteen bacterial taxa, including p_Firmicutes.c_Clostridia, displayed protective associations with the risk of ALS, whereas sixteen showed harmful associations. Mediation analysis suggested that p_Firmicutes.c_Clostridia may confer protection through CD33+HLA-DR-myeloid-derived suppressor cell upregulation (23.8% mediation effect). Experimental validation confirmed fewer myeloid-derived suppressor cells in ALS patients (4.0 ± 0.8% vs. 7.5 ± 1.0%, p < 0.001, Cohen's d = 1.4) and lower levels of anti-inflammatory cytokines (TGF-β1: Cohen's d = 1.8, p < 0.001).

conclusionsThese findings support causal associations between gut microbial taxa and the ALS risk, which are mediated through immunoregulatory mechanisms, highlighting therapeutic targets within the gut‒immune‒brain axis.

Indexed as

Amyotrophic Lateral SclerosisGastrointestinal MicrobiomeNeuroinflammatory DiseasesAgedCytokinesFemaleGenomicsHumansMaleMendelian Randomization AnalysisMiddle AgedMyeloid-Derived Suppressor CellsCytokinesAmyotrophic lateral sclerosisCausal inferenceGut microbiotaImmune cellsMendelian randomizationMicrobiome‒gut‒brain axis

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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.