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探索肠道微生物群共丰度与不同亚型肠易激综合征新代谢途径之间的关系:来自美国肠道计划的见解

Exploring the relationship between co-abundance of gut microbiota and novel metabolic pathways in different subtypes of irritable bowel syndrome: insights from the American Gut Project.

作者信息

Han Li-Li, Mei Chun-Feng, Xue Hong

机构信息

Digestive Laboratory of Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xi-yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Front Med (Lausanne). 2025 Jul 22;12:1615717. doi: 10.3389/fmed.2025.1615717. eCollection 2025.


DOI:10.3389/fmed.2025.1615717
PMID:40766067
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12321851/
Abstract

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder with an unclear etiology. Recent studies have underscored the association between alterations in the gut microbiome and the pathogenesis of IBS. However, limited knowledge exists regarding the co-abundance patterns of gut microbiota and metabolic pathways across different IBS subtypes. METHODS: In this study, we utilized the comprehensive gut microbiome data from the American Gut Project (AGP). Through Spearman correlation analysis, the random forest model, SHAP analysis, and the PICRUSt2 prediction function, we constructed and screened the gut microbiota co-abundance groups and their metabolic characteristics of three cohorts of patients with different subtypes among cohorts of patients with three distinct IBS subtypes: predominant constipation (IBS-C), predominant diarrhea (IBS-D), and unclassified (IBS-U), as well as three non-IBS control groups (non-IBS1, non-IBS2, and non-IBS3, respectively). RESULTS: Our study findings indicate that, in comparison to their respective non-IBS groups, there was a significant difference in the prevalence of 37.5% specific co-abundance groups (CAGs) identified across all three IBS subtypes: IBS-C, IBS-D, and IBS-U. In addition, the random forest model shows that there are 2-4 characteristic CAGs for each subtype. We also analyzed the co-abundance networks between each CAG and metabolic pathways. Additionally, we analyzed the co-abundance networks between each CAG and metabolic pathways. No significant species-metabolic pathway co-abundance groups were found in the IBS-C group. In the IBS-D group, 50% of CAGs showed significantly different co-abundance with related metabolic pathways compared to the non-IBS control groups, while in the IBS-U group, this figure was 80%. Through the analysis of differentially expressed metabolic pathways, we revealed significant disturbances in SCFAs and LPS metabolic pathways (particularly a marked increase in acetate) in IBS-D patients, whereas IBS-U patients only exhibited a non-significant downward trend in tryptophan metabolic pathways. CONCLUSION: These results indicate that the alterations in the gut microbiota and their associated metabolic pathways differ among IBS subtypes, leading to distinct developments and symptoms. This expands our current understanding of the gut microbiota in different IBS subtypes and provides a theoretical foundation for further research.

摘要

背景:肠易激综合征(IBS)是一种常见的功能性胃肠疾病,病因尚不明确。最近的研究强调了肠道微生物群改变与IBS发病机制之间的关联。然而,关于不同IBS亚型中肠道微生物群和代谢途径的共丰度模式的了解有限。 方法:在本研究中,我们利用了来自美国肠道项目(AGP)的综合肠道微生物群数据。通过Spearman相关性分析、随机森林模型、SHAP分析和PICRUSt2预测功能,我们构建并筛选了三个不同IBS亚型队列(以便秘为主型(IBS-C)、以腹泻为主型(IBS-D)和未分类型(IBS-U))以及三个非IBS对照组(分别为non-IBS1、non-IBS2和non-IBS3)患者的肠道微生物群共丰度组及其代谢特征。 结果:我们的研究结果表明,与各自的非IBS组相比,在所有三种IBS亚型(IBS-C、IBS-D和IBS-U)中鉴定出的37.5%的特定共丰度组(CAGs)的患病率存在显著差异。此外,随机森林模型显示每个亚型有2-4个特征性CAGs。我们还分析了每个CAG与代谢途径之间的共丰度网络。此外,我们分析了每个CAG与代谢途径之间的共丰度网络。在IBS-C组中未发现显著的物种-代谢途径共丰度组。在IBS-D组中,50%的CAGs与相关代谢途径的共丰度与非IBS对照组相比有显著差异,而在IBS-U组中,这一数字为80%。通过对差异表达代谢途径的分析,我们发现IBS-D患者的短链脂肪酸和脂多糖代谢途径存在显著紊乱(尤其是乙酸盐显著增加),而IBS-U患者仅在色氨酸代谢途径中呈现不显著的下降趋势。 结论:这些结果表明,肠道微生物群及其相关代谢途径的改变在IBS亚型之间存在差异,导致不同的发展和症状。这扩展了我们目前对不同IBS亚型中肠道微生物群的理解,并为进一步研究提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1d0/12321851/620712190fe8/fmed-12-1615717-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1d0/12321851/c9e5b2cdef6f/fmed-12-1615717-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1d0/12321851/620712190fe8/fmed-12-1615717-g008.jpg

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本文引用的文献

[1]
Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.

Nat Microbiol. 2024-8

[2]
The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.

J Transl Med. 2024-1-23

[3]
Association analysis of the gut microbiota in predicting outcomes for patients with acute ischemic stroke and H-type hypertension.

Front Neurol. 2023-10-26

[4]
Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

Genome Biol. 2023-10-12

[5]
Histamine-producing bacteria and their role in gastrointestinal disorders.

Expert Rev Gastroenterol Hepatol. 2023

[6]
Effect of Plant-Based Diets on Gut Microbiota: A Systematic Review of Interventional Studies.

Nutrients. 2023-3-21

[7]
Gut microbiome signatures reflect different subtypes of irritable bowel syndrome.

Gut Microbes. 2023

[8]
Probiotics modulate gastrointestinal microbiota after eradication: A multicenter randomized double-blind placebo-controlled trial.

Front Immunol. 2022

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Distinctions Between Fecal and Intestinal Mucosal Microbiota in Subgroups of Irritable Bowel Syndrome.

Dig Dis Sci. 2022-12

[10]
Roseburia hominis Alleviates Neuroinflammation via Short-Chain Fatty Acids through Histone Deacetylase Inhibition.

Mol Nutr Food Res. 2022-9

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