Fecal bile acid dysmetabolism and reduced ursodeoxycholic acid correlate with novel microbial signatures in feline chronic kidney disease.

IF 4 2区 生物学 Q2 MICROBIOLOGY
Frontiers in Microbiology Pub Date : 2024-10-21 eCollection Date: 2024-01-01 DOI:10.3389/fmicb.2024.1458090
John C Rowe, Stacie C Summers, Jessica M Quimby, Jenessa A Winston
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引用次数: 0

Abstract

Background: Microbial-derived secondary bile acids (SBAs) are reabsorbed and sensed via host receptors modulating cellular inflammation and fibrosis. Feline chronic kidney disease (CKD) occurs with progressive renal inflammation and fibrosis, mirroring the disease pathophysiology of human CKD patients.

Methods: Prospective cross-sectional study compared healthy cats (n = 6) with CKD (IRIS Stage 2 n = 17, Stage 3 or 4 n = 11). Single timepoint fecal samples from all cats underwent targeted bile acid metabolomics. 16S rRNA gene amplicon sequencing using DADA2 with SILVA taxonomy characterized the fecal microbiota.

Results: CKD cats had significantly reduced fecal concentrations (median 12.8 ng/mg, Mann-Whitney p = 0.0127) of the SBA ursodeoxycholic acid (UDCA) compared to healthy cats (median 39.4 ng/mg). Bile acid dysmetabolism characterized by <50% SBAs was present in 8/28 CKD and 0/6 healthy cats. Beta diversity significantly differed between cats with <50% SBAs and > 50% SBAs (PERMANOVA p < 0.0001). Twenty-six amplicon sequence variants (ASVs) with >97% nucleotide identity to Peptacetobacter hiranonis were identified. P. hiranonis combined relative abundance was significantly reduced (median 2.1%) in CKD cats with <50% SBAs compared to CKD cats with >50% SBAs (median 13.9%, adjusted p = 0.0002) and healthy cats with >50% SBAs (median 15.5%, adjusted p = 0.0112). P. hiranonis combined relative abundance was significantly positively correlated with the SBAs deoxycholic acid (Spearman r = 0.5218, adjusted p = 0.0407) and lithocholic acid (Spearman r = 0.5615, adjusted p = 0.0156). Three Oscillospirales ASVs and a Roseburia ASV were also identified as significantly correlated with fecal SBAs.

Clinical and translational importance: The gut-kidney axis mediated through microbial-derived SBAs appears relevant to the spontaneous animal CKD model of domestic cats. This includes reduced fecal concentrations of the microbial-derived SBA UDCA, known to regulate inflammation and fibrosis and be reno-protective. Microbes correlated with fecal SBAs include bai operon containing P. hiranonis, as well as members of Oscillospirales, which also harbor a functional bai operon. Ultimately, CKD cats represent a translational opportunity to study the role of SBAs in the gut-kidney axis, including the potential to identify novel microbial-directed therapeutics to mitigate CKD pathogenesis in veterinary patients and humans alike.

猫慢性肾病患者粪便胆汁酸代谢紊乱和熊去氧胆酸减少与新型微生物特征相关。
背景:微生物衍生的次级胆汁酸(SBAs)可被重吸收,并通过宿主受体调节细胞炎症和纤维化。猫慢性肾脏病(CKD)会出现进行性肾脏炎症和纤维化,这与人类慢性肾脏病患者的病理生理学相似:前瞻性横断面研究比较了健康猫(n = 6)与 CKD(IRIS 2 期 n = 17,3 期或 4 期 n = 11)。对所有猫的单时间点粪便样本进行了靶向胆汁酸代谢组学研究。使用 DADA2 和 SILVA 分类法进行 16S rRNA 基因扩增片段测序,以确定粪便微生物群的特征:结果:与健康猫(中位数为 39.4 ng/mg)相比,CKD 猫粪便中 SBA 熊去氧胆酸 (UDCA) 的浓度明显降低(中位数为 12.8 ng/mg,Mann-Whitney p = 0.0127)。胆汁酸代谢障碍的特征是 50%的 SBAs(PERMANOVA p 97%的核苷酸与 Peptacetobacter hiranonis 相同)被鉴定出来。在 SBA 含量为 50% 的 CKD 猫(中位数为 13.9%,调整后 p = 0.0002)和 SBA 含量大于 50% 的健康猫(中位数为 15.5%,调整后 p = 0.0112)中,P. hiranonis 综合相对丰度显著降低(中位数为 2.1%)。P.hiranonis的综合相对丰度与SBA脱氧胆酸(Spearman r = 0.5218,调整后p = 0.0407)和石胆酸(Spearman r = 0.5615,调整后p = 0.0156)呈显著正相关。此外,还发现三种鞘翅目 ASV 和一种蔷薇属 ASV 与粪便 SBAs 显著相关:通过微生物衍生的 SBAs 介导的肠道-肾脏轴似乎与家猫的自发动物性 CKD 模型相关。这包括粪便中微生物衍生的 SBA UDCA 浓度的降低,众所周知,这种 SBA UDCA 可调节炎症和纤维化,并具有肾保护作用。与粪便 SBAs 相关的微生物包括含有 bai 操作子的 P. hiranonis,以及同样携带功能性 bai 操作子的 Oscillospirales 成员。最终,CKD 猫是研究 SBAs 在肠道-肾脏轴中作用的一个转化机会,包括确定新型微生物导向疗法的潜力,以减轻兽医患者和人类的 CKD 发病机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.70
自引率
9.60%
发文量
4837
审稿时长
14 weeks
期刊介绍: Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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