Multiomic Integration Reveals Taxonomic Shifts Correlate to Serum Cytokines in an Antibiotics Model of Gut Microbiome Disruption.

IF 3.5 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2025-08-24 eCollection Date: 2025-10-01 DOI:10.1007/s12195-025-00861-2

Cameron X Villarreal, Deva D Chan

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引用次数: 0

Abstract

Purpose: The gut microbiome interacts with many systems throughout the human body. Microbiome disruption reduces bone tissue mechanics but paradoxically slows osteoarthritis progression. The microbiome also mediates inflammatory and immune responses, including serum cytokines. Towards our long-term goal of studying how the gut microbiome interacts with synovial joint health and disease, we examined how antibiotics-induced changes to microbial taxa abundance associated to serum cytokine levels.

Methods: Mice (n = 5 + ) were provided ad libitum access to water containing antibiotics (1 g/L neomycin, 1 g/L ampicillin, or 1 g/L ampicillin with 0.5 g/L neomycin) or control water from 5- to 16-weeks old, corresponding in skeletal development to ~ 10 to ~ 25 years in humans. At humane euthanasia, we collected cecum contents for 16S metagenomics and blood for serum cytokine quantification for comparison to control and among antibiotic groups. We used dimensional reduction techniques, multiomic integration, and correlation to discriminate antibiotic groups and identify specific relationships between high-abundance taxa and serum cytokines.

Results: Antibiotic treatment significantly lowered diversity, altered phylum relative abundance, and resulted in significant association with specific taxa. Dimensional reduction techniques and multiomic integration revealed distinct antibiotic-associated clusters based on genera relative abundance and cytokine serum concentration. Cytokines IL-6, MIP-1B, and IL-10 significantly contributed to antibiotic discrimination, significantly different among antibiotic treatments, and had significant correlations with specific taxa.

Conclusions: Antibiotic treatment resulted in heterogenous response in gut microbiome and serum cytokines, allowing significant microbe-cytokine links to emerge. The relationships identified here will enable further investigation of the gut microbiome's role in modifying joint health and disease.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-025-00861-2.

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多组学整合揭示了肠道微生物群破坏的抗生素模型中与血清细胞因子相关的分类转移。

目的：肠道微生物组与整个人体的许多系统相互作用。微生物群的破坏降低了骨组织力学，但矛盾的是减缓了骨关节炎的进展。微生物组也介导炎症和免疫反应，包括血清细胞因子。为了研究肠道微生物群如何与滑膜关节健康和疾病相互作用的长期目标，我们研究了抗生素诱导的微生物类群丰度变化与血清细胞因子水平的关系。方法：小鼠（n = 5 +）在5 ~ 16周龄（相当于人类骨骼发育~ 10 ~ 25岁）时，可随意饮用含抗生素（1 g/L新霉素、1 g/L氨苄西林或1 g/L氨苄西林加0.5 g/L新霉素）的水或对照水。在人道安乐死时，我们收集盲肠内容物进行16S宏基因组学分析，并采集血液进行血清细胞因子定量分析，用于对照组和抗生素组之间的比较。我们使用降维技术、多组整合和相关性来区分抗生素群，并确定高丰度分类群与血清细胞因子之间的特定关系。结果：抗生素治疗显著降低了物种多样性，改变了门的相对丰度，并导致与特定分类群的显著关联。基于属的相对丰度和细胞因子的血清浓度，降维技术和多组学整合显示出不同的抗生素相关簇。细胞因子IL-6、MIP-1B和IL-10对抗生素的区分有显著影响，在不同的抗生素处理中差异显著，且与特定分类群有显著相关性。结论：抗生素治疗导致肠道微生物组和血清细胞因子的异质性反应，允许显著的微生物-细胞因子联系出现。这里确定的关系将有助于进一步研究肠道微生物组在改变关节健康和疾病中的作用。补充信息：在线版本包含补充资料，可在10.1007/s12195-025-00861-2获得。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.