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The role of gut microbiota and indole metabolite in cats with chronic kidney disease
Chronic kidney disease,gut microbiota,next generation sequencing,cats,indole,indoxyl sulfate,
|Publication Year :||2018|
|Abstract:||腸道微生物於宿主健康中扮演重要角色，其參與宿主之物質代謝、養分吸收，並與疾病的發生有關聯。近年來許多研究發現腸道菌與慢性腎臟病 (chronic kidney disease, CKD) 之間存在著關聯性。慢性腎臟病期間由於腎臟功能受損，無法有效率地將尿毒素藉由尿液排出體外，導致毒素累積於體內，在腎臟病患者及動物模式生物研究中發現尿毒素的累積會導致腸道微生物菌相的變化並可能會破壞腸道屏蔽。硫酸吲哚酚 (indoxyl sulfate, IS) 是一種尿毒素，其來源是透過在腸道的微生物將來自飲食中的色氨酸發酵產生吲哚 (indole)，吲哚經由腸道吸收進入血液循環並在肝臟被代謝成硫酸吲哚酚。慢性腎臟病在貓是一個常見的疾病，更是造成貓死亡的疾病之一，因此本研究目的為探討貓慢性腎臟病與腸道菌相及吲哚代謝產物之關聯性。慢性腎臟病貓與健康貓之血液及糞便於同一天收集，並以高效液相層析法分析糞便中吲哚及血液中硫酸吲哚酚之濃度；一部分糞便經純化DNA後，以次世代定序 (next generation sequencing, NGS) 比較慢性腎臟病貓及健康貓的腸道菌群。另外於體外實驗以不同濃度之吲哚處理Caco-2細胞株，探討吲哚對於腸道屏蔽之影響。結果顯示糞便中的吲哚及血液中硫酸吲哚酚濃度在慢性腎臟貓組別較高，且兩者之間存在顯著的相關性。腸道菌相結果顯示，在腎臟病貓中的菌相多樣性有顯著性下降，且Enterobacteriaceae相較於在健康貓之菌量有顯著性較高；而Faecalibacterium prausnitzii、Sutterella spp.，及 Prevotella copri 則在腎臟病貓中有顯著性降低。體外實驗結果顯示高濃度的吲哚可以增加腸細胞屏蔽的完整性。綜合上述結果，慢性腎臟病的確會使貓腸道菌相產生變化，且伴隨著吲哚及其代謝物濃度的提升，但吲哚並不會造成腸道屏蔽的破壞。|
Chronic kidney disease (CKD) is one of the most influential causes of morbidity and mortality in cats. A growing number of studies have highlighted the relationship between the kidney and gastrointestinal microbiota in patients with CKD. During CKD, a large number of uremic toxins derived from increased bacterial fermentation of proteins are accumulated in the body. Retention of uremic toxins has been associated with damage of the intestinal epithelial barrier and alteration of gut microbiota in CKD rats and human patients. Indoxyl sulfate, one of the uremic toxins, is produced by the breakdown of indole, which is from the fermentation of tryptophan by microbiomes in the intestine. No studies of the gut microbiota and its metabolite in cats with CKD have been investigated. Therefore, the objectives of this study were to compare the composition of fecal microbiota in CKD and non-CKD cats, and to determine the concentration of indole as well as indoxyl sulfate. The effect of indole on the integrity of intestinal barrier was also studied. Fecal samples were collected from CKD and corresponding control cats, and each sample was analyzed by Illumina sequencing of the 16S rRNA gene. Total bacterial diversity in feces was significantly reduced in CKD cats compared to the control group. Based on the unweighted UniFrac distance metric, the composition of fecal microbiota in cats with CKD and the control group was significantly different. Heat map, linear discriminate analysis, and 2-fold-change analysis identified an enrichment of Enterobacteriaceae in CKD groups whereas Faecalibacterium prausnitzii, Sutterella spp., and Prevotella copri were more prevalent in the control group. On the other hand, concentrations of indole and indoxyl sulfate were higher in cats with CKD compared to the controls. In vitro, the expression of tight junction proteins and the integrity of intestinal epithelium was increased by treating higher concentration of indole. In conclusion, the composition of fecal microbiota was altered by the presence of CKD in cats, followed by the increased concentration of indole and IS. While increased concentration of indole may not cause the damage of intestinal epithelium. However, further studies are needed to provide more conclusive evidence.
|Appears in Collections:||生物科技研究所|
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