Fecal Microbial Profiles and Short-Chain Fatty Acid/Bile Acid Metabolomics in Patients With Age-Related Macular Degeneration: A Pilot Study.

IF 5 2区 医学 Q1 OPHTHALMOLOGY
Zaid Parekh, Jason Xiao, Amir Mani, Quadis Evans, Christopher Phung, Hugo A Barba, Bingqing Xie, Ashley M Sidebottom, Anitha Sundararajan, Huaiying Lin, Ramanujam Ramaswamy, David Dao, Reem Gonnah, Madeleine Yehia, Seenu M Hariprasad, Mark D'Souza, Dinanath Sulakhe, Eugene B Chang, Dimitra Skondra
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Abstract

Purpose: Age-related macular degeneration (AMD) is a multifactorial disease, and studies have implicated the role of gut microbiota in its pathogenesis. However, characterization of microbiome dysbiosis and associated microbial-derived metabolomic profiles across AMD stages remains unknown. In this pilot study, we explored how gut microbiome composition and gut-derived metabolites differ in AMD.

Methods: Our pilot study analyzed fasted stool samples that were collected from 22 patients at a tertiary academic center. Subjects were classified as control, intermediate AMD, or advanced AMD based on clinical presentation. 16S rRNA amplicon sequencing and standard chromatography-mass spectrometry methods were used to identify bacterial taxonomy composition and abundance of short-chain fatty acids (SCFAs) and bile acids (BAs), respectively. Genetic testing was used to investigate the frequency of 14 high-risk single nucleotide polymorphisms (SNPs) associated with AMD in the AMD cohort.

Results: Forty-three differentially abundant genera were present among the control, intermediate, and advanced groups. Taxa with known roles in immunologic pathways, such as Desulfovibrionales (q = 0.10) and Terrisporobacter (q = 1.16e-03), were in greater abundance in advanced AMD patients compared to intermediate. Advanced AMD patients had decreased abundance of 12 SCFAs, including acetate (P = 0.002), butyrate (P = 0.04), and propionate (P = 0.01), along with 12 BAs, including taurocholic acid (P = 0.02) and tauroursodeoxycholic acid (P = 0.04). Frequencies of high-risk SNPs were not significantly different between the intermediate and advanced AMD groups.

Conclusions: This pilot study identifies distinct gut microbiome compositions and metabolomic profiles associated with AMD and its stages, providing preliminary evidence of a potential link between gut microbiota and AMD pathogenesis. To validate these findings and elucidate the underlying mechanisms, future research with larger cohorts and more comprehensive sampling is strongly recommended.

年龄相关性黄斑变性患者的粪便微生物谱和短链脂肪酸/胆汁酸代谢组学:一项初步研究
目的:年龄相关性黄斑变性(AMD)是一种多因素疾病,研究表明肠道微生物群在其发病机制中的作用。然而,微生物群落失调的特征和相关的微生物衍生代谢组学特征在AMD的各个阶段仍然未知。在这项初步研究中,我们探讨了肠道微生物组成和肠道衍生代谢物在AMD中的差异。方法:我们的初步研究分析了从一个三级学术中心收集的22例患者的空腹粪便样本。根据临床表现将受试者分为对照组、中度AMD和晚期AMD。采用16S rRNA扩增子测序和标准色谱-质谱法分别鉴定细菌的分类组成和短链脂肪酸(SCFAs)和胆汁酸(BAs)的丰度。基因检测用于调查AMD队列中与AMD相关的14种高危单核苷酸多态性(snp)的频率。结果:对照组、中间组和晚期组存在43个差异丰度属。已知在免疫途径中起作用的类群,如Desulfovibrionales (q = 0.10)和Terrisporobacter (q = 1.16e-03),在晚期AMD患者中的丰度高于中度AMD患者。晚期AMD患者有12种scfa丰度降低,包括乙酸(P = 0.002)、丁酸(P = 0.04)和丙酸(P = 0.01),以及12种BAs,包括牛磺酸胆酸(P = 0.02)和牛磺酸去氧胆酸(P = 0.04)。高危snp的频率在中晚期AMD组之间无显著差异。结论:这项初步研究确定了与AMD及其阶段相关的不同肠道微生物组成和代谢组学特征,为肠道微生物群与AMD发病机制之间的潜在联系提供了初步证据。为了验证这些发现并阐明潜在的机制,强烈建议未来进行更大的队列和更全面的抽样研究。
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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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