Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice.

IF 6.2 2区 医学 Q1 NEUROSCIENCES Acta Neuropathologica Communications Pub Date : 2024-11-06 DOI:10.1186/s40478-024-01877-x
Elena Niccolai, Leandro Di Gloria, Maria Chiara Trolese, Paola Fabbrizio, Simone Baldi, Giulia Nannini, Cassandra Margotta, Claudia Nastasi, Matteo Ramazzotti, Gianluca Bartolucci, Caterina Bendotti, Giovanni Nardo, Amedeo Amdei
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Abstract

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

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宿主遗传学和肠道微生物群影响脂质代谢和炎症:对 SOD1G93A 小鼠 ALS 病理生理学的潜在影响。
肌萎缩侧索硬化症(ALS)是一种以运动神经元进行性丧失为特征的破坏性神经退行性疾病,其复杂的发病机制与遗传和环境因素有关。免疫反应失调和能量代谢改变是其主要特征,有新的证据表明肠道微生物群(GM)与疾病进展有关。我们在两种不同的 ALS 小鼠模型中研究了遗传背景、GM 组成、新陈代谢和免疫反应之间的相互作用:利用 16 S rRNA 测序和粪便代谢物分析,我们描述了这两个品系的非转基因(Ntg)和 SOD1G93A 突变小鼠的肠道微生物群组成和代谢物特征。我们的研究结果表明,转基因小鼠的转基因组成和功能存在品系特异性差异,尤其是在粪便样本中属于Erysipelotrichaceae的类群丰度以及短链和中链脂肪酸水平方面。SOD1突变会导致两个品系的基因组定植发生显著变化,C57Ola_G93A小鼠的变化与129 Sv小鼠相似,可能会影响疾病的发病机制。我们的发现强调了遗传背景对 ALS 小鼠模型中基因组的组成、代谢和免疫反应的重大影响。这些品系特异性差异可能会导致疾病易感性和进展率的不同。进一步阐明这些相互作用的内在机制可为了解 ALS 发病机制和潜在治疗靶点提供新的视角。
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来源期刊
Acta Neuropathologica Communications
Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine
CiteScore
11.20
自引率
2.80%
发文量
162
审稿时长
8 weeks
期刊介绍: "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.
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