The gut microbiota in kidney disease

doi:10.1126/science.abd8344

GSTDTAP > 气候变化

DOI	10.1126/science.abd8344
	The gut microbiota in kidney disease
	Jennifer L. Pluznick
	2020-09-18
发表期刊	Science
出版年	2020
英文摘要	Chronic kidney disease affects 9% of the global population ([ 1 ][1]) and can have severe impacts on both the individual and societal levels. Although various conditions, such as diabetes, are well known risk factors for chronic kidney disease, in recent years interest has been growing regarding a potential role for the gut microbiota in modulating outcomes in kidney disease ([ 2 ][2]). Simultaneously, in the microbiology field, there has been a growing appreciation for the intersection of diet and the gut microbiota as a driver of changes in host health ([ 3 ][3]). To date, a common model has been that diet acts to alter the relative abundances (or diversity) of gut microbes, which can then lead to changes in gut microbial metabolite production ([ 4 ][4]). However, on page 1518 of this issue, Lobel et al. ([ 5 ][5]) report that diet can posttranslationally modify the gut microbial proteome, which can alter microbial metabolite production to drive changes in renal function. The primary function of the kidney is to maintain homeostasis against the many insults and challenges from the external and internal environment. Functions including acid-base balance, water balance, blood pressure regulation, and glucose homeostasis require exquisite coordination and regulation by the kidney. Thus, it is not surprising that when kidney function falters, chronic kidney disease is associated with symptoms that are emblematic of the wide influence of renal function on health, including uremia (the retention of waste products in the blood that would normally be excreted in the urine), as well as edema, acidosis, anemia, and bone disease. ![Figure][6] Dietary influences on gut microbiota The diet can modulate the gut microbial taxa (represented by different colors), thereby influencing metabolite production (left side of the figure). By contrast, Lobel et al. find that diet does not modulate the bacterial taxa, but rather posttranslationally influences the bacterial proteome, which alters microbial metabolite production (right side of the figure). GRAPHIC: X. LIU/ SCIENCE Risk factors for chronic kidney disease include conditions such as diabetes, hypertension, and heart disease. In addition to these comorbidities, the progression of kidney disease can be strongly influenced by dietary modulations—for example, the DASH (dietary approaches to stop hypertension) diet has shown to be protective ([ 6 ][7]). The positive influence of the DASH diet on kidney disease progression has been suggested to be due to a lowering of blood pressure, a lowered dietary acid load, and/or a lower likelihood of promoting inflammation and endothelial cell dysfunction ([ 6 ][7]). A low-protein diet is another dietary intervention used in chronic kidney disease patients, and a benefit of this approach appears to be a decrease in uremic toxins. Uremic toxins are compounds that are retained in the blood when kidney function is compromised, and increases in uremic toxins promote a variety of pathologies, including endothelial dysfunction. Because gut microbes produce uremic toxins (including p-cresyl sulfate, indole and indole derivatives, and trimethylamine N -oxide), the production or modulation of these substances by gut microbes has also been a focus of research ([ 7 ][8]). Although the role of the gut microbiota to produce uremic toxins is well-known, Lobel et al. introduce an entirely new twist on this paradigm: the idea that dietary changes can trigger posttranslational modifications of microbial proteins that alter uremic toxin formation, and thereby influence chronic kidney disease progression. Specifically, Lobel et al. report a dietary intervention that induced a posttranslational modification (S-sulfhydration) of a microbial enzyme, leading to a decrease in uremic toxin production that had a protective effect in a mouse model of kidney disease. This is a notable finding because posttranslational changes drove this outcome, and the gut microbial community composition itself was not found to be altered (see the figure). In recent years, a number of studies have shown that changes in the gut microbiota (typically, changes in the relative proportion of various bacteria) are associated with a wide diversity of diseases and conditions, including obesity, diabetes, bipolar disorder, and depression. However, many of these studies have been correlative—they have reported shifts in bacterial abundances in affected individuals, but it is often unclear why these shifts occur, or whether they are causal. Are the shifts somehow promoting the associated phenotype? Or are they reacting to it? In at least one case, a change in bacterial abundance in type 2 diabetes was tied to a pharmaceutical intervention common in the affected group, rather than a consequence of the disease itself ([ 8 ][9]), highlighting the complexity inherent in these studies. To move research forward, it is imperative that studies go beyond reporting associations, and begin to unravel mechanisms underlying these shifts, and to understand the consequences. The study of Lobel et al. goes a step beyond the taxonomic approach by highlighting the idea that a “shift” in bacterial composition is not the only explanation for a change in function of the gut microbiota. If posttranslational modifications of the bacterial proteome modulate host physiology or pathophysiology, then simply determining bacterial abundance will not reveal all of the key information. In retrospect, this should not be surprising: In mammalian research, it has been known for decades that the relative abundance of messenger RNA (mRNA) is not informative about everything that is happening at the protein, posttranslational, or functional level. Similarly, it is not surprising that, for some situations, species-level abundances of gut microbes fail to provide the full picture of what is happening in health and disease. The findings of Lobel et al. emphasize the importance of not simply measuring bacterial abundances, but instead truly understanding functional processes that underlie host–microbiota interactions. Although such studies are difficult, Lobel et al. provide a blueprint for how they can be accomplished. Furthermore, these studies imply that the progression of chronic kidney disease may be modified by new strategies that alter the gut microbiota and/or the enzymatic activities of the gut microbial proteome. Looking ahead, these types of approaches can yield dividends for not only chronic kidney disease, but for a large array of other diseases and conditions for which the microbiota have been implicated. By definition, these types of studies require a multidisciplinary approach as one must be cognizant of not only microbial biology and posttranslational modification modalities but must also understand the whole-animal physiology and pathophysiology of disease. Thus, this represents a great opportunity for scientists from diverse fields to come together. By pooling the diverse knowledge and approaches of varied fields, advances in understanding of host–microbiome interactions and disease progression can be made, and perhaps new approaches to disease treatment and prevention can be uncovered. 1. [↵][10]G. B. D. C. K. D. Collaboration, Lancet 395, 709 (2020). [OpenUrl][11][CrossRef][12][PubMed][13] 2. [↵][14]1. S. Noel et al ., Nephron Clin. Pract. 127, 139 (2014). 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领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：20[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/295411
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jennifer L. Pluznick. The gut microbiota in kidney disease[J]. Science,2020.
APA	Jennifer L. Pluznick.(2020).The gut microbiota in kidney disease.Science.
MLA	Jennifer L. Pluznick."The gut microbiota in kidney disease".Science (2020).