Gut Microbiota-Kidney Cross-Talk in Acute Kidney Injury

Gong, Jing; Noel, Sanjeev; Pluznick, Jennifer L.; Hamad, Abdel Rahim A.; Rabb, Hamid

doi:10.1016/j.semnephrol.2018.10.009

Cited by 81 publications

(86 citation statements)

References 95 publications

(102 reference statements)

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“…In our study, we were interested in interpreting the extensive intra-subject variability of post-I/R creatinine concentration. Although during renal I/R many parameters can affect the severity of AKI, there are some reasons to consider microbiome as one of the possible factors playing a role in this issue [32,33]. All our main findings are summarized in Figure 4.…”

Section: Discussionmentioning

confidence: 70%

Microbiome-Metabolome Signature of Acute Kidney Injury

et al. 2020

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Intestinal microbiota play a considerable role in the host’s organism, broadly affecting its organs and tissues. The kidney can also be the target of the microbiome and its metabolites (especially short-chain fatty acids), which can influence renal tissue, both by direct action and through modulation of the immune response. This impact is crucial, especially during kidney injury, because the modulation of inflammation or reparative processes could affect the severity of the resulting damage or recovery of kidney function. In this study, we compared the composition of rat gut microbiota with its outcome, in experimental acute ischemic kidney injury and named the bacterial taxa that play putatively negative or positive roles in the progression of ischemic kidney injury. We investigated the link between serum creatinine, urea, and a number of metabolites (acylcarnitines and amino acids), and the relative abundance of various bacterial taxa in rat feces. Our analysis revealed an increase in levels of 32 acylcarnitines in serum, after renal ischemia/reperfusion and correlation with creatinine and urea, while levels of three amino acids (tyrosine, tryptophan, and proline) had decreased. We detected associations between bacterial abundance and metabolite levels, using a compositionality-aware approach—Rothia and Staphylococcus levels were positively associated with creatinine and urea levels, respectively. Our findings indicate that the gut microbial community contains specific members whose presence might ameliorate or, on the contrary, aggravate ischemic kidney injury. These bacterial taxa could present perspective targets for therapeutical interventions in kidney pathologies, including acute kidney injury.

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Section: Discussionmentioning

confidence: 70%

Microbiome-Metabolome Signature of Acute Kidney Injury

et al. 2020

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“…Although the incidence is difficult to estimate due to variable patient characteristics, many newly developed drugs have distinct mechanisms of nephrotoxicity, making it the second most common cause of hospital-acquired AKI (4). Recent studies have revealed a close relationship between the gut microbiome and various kidney diseases; however, the association between intestinal bacteria and nephrotoxic AKI remains unclear (6,7).…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus salivarius BP121 prevents cisplatin‑induced acute kidney injury by inhibition of uremic toxins such as indoxyl sulfate and p‑cresol sulfate via alleviating dysbiosis

Lee¹,

Park

Kim³

et al. 2020

Int J Mol Med

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The gut microbiota is important for maintaining the integrity of the intestinal barrier, promoting immunological tolerance and carrying out metabolic activities that have not evolved in hosts. Intestinal dysbiosis is associated with chronic kidney disease and probiotic supplementation has been shown to be beneficial. However, it is not known whether gut microorganisms-specifically, lactic acid bacteria (LAB) can protect against acute kidney injury (AKI). To address this issue, the present study investigated the effects of Lactobacillus salivarius BP121, an intestinal LAB isolated from the feces of newborns, in a rat model of cisplatin-induced AKI and also in Caco-2 human intestinal epithelial cells. BP121 prevented cisplatin-induced AKI in rats, as demonstrated by decreases in inflammation and oxidative stress in kidney tissue and in serum levels of uremic toxins such as indoxyl sulfate (IS) and p-cresol sulfate (PCS). BP121 also reduced intestinal permeability, as determined using fluorescein isothiocyanate-dextran by immunohistochemical detection of tight junction (TJ) proteins such as zona occludens-1 and occludin. The abundance of Lactobacillus spp., which are beneficial intestinal flora, was increased by BP121; this was accompanied by an increase in the concentrations of short-chain fatty acids in feces. Additionally, H 2 O 2 -induced TJ protein damage was reduced in Caco-2 cells treated with BP121 culture supernatant, an effect that was reversed by the 5' AMP-activated protein kinase (AMPK) inhibitor Compound C and Toll-like receptor (TLR)4 inhibitor TLR4-IN-C34. In conclusion, this study demonstrated that L. salivarius BP121 protects against cisplatin-induced AKI by decreasing inflammation and oxidative stress and this renoprotective effect is partially mediated by modulating the gut environment and thereby suppressing IS and PCS production as well as by regulating AMPK and TLR4 dependent TJ assembly.

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“…In contrary, depletion of mouse gut microbiota by an antibiotic-cocktail significantly attenuates I/R-induced AKI associated with low expression of F4/80 macrophages and pro-inflammatory chemokines [ 89 ]. Intestinal microbiota modulates immune reactions in AKI through their metabolites such as short chain fatty acids, trimethylamine-N-Oxide, and D-amino acids [ 86 , 90 ]. While it is known that there is a gut-kidney cross talk, it has only recently been demonstrated that AKI can influence intestinal microbiomes.…”

Section: The Differences In Gut Microbiota Among Rodents Large Animamentioning

confidence: 99%

Large animal models for translational research in acute kidney injury

et al. 2020

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While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.

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Gut Microbiota-Kidney Cross-Talk in Acute Kidney Injury

Cited by 81 publications

References 95 publications

Microbiome-Metabolome Signature of Acute Kidney Injury

Microbiome-Metabolome Signature of Acute Kidney Injury

Lactobacillus salivarius BP121 prevents cisplatin‑induced acute kidney injury by inhibition of uremic toxins such as indoxyl sulfate and p‑cresol sulfate via alleviating dysbiosis

Large animal models for translational research in acute kidney injury

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