Gut Microbiota In Chronic Kidney Disease Research Articles

The compositional and functional imbalance of the gut microbiota in CKD linked to disease patterns

BackgroundThe prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes.MethodsWe conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups.ResultsThe CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD.ConclusionsThe dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD.

Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

ABSTRACT Background: The gut microbiota is closely associated with chronic kidney disease (CKD) development and prognosis. However, a comprehensive understanding of publication trends and research focuses within this domain remains limited. This study aimed to elucidate the relationship between the gut microbiota and CKD through a bibliometric analysis. Methods: Literature published between 2001 and 2022 on gut microbiota and CKD was obtained from the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer and CiteSpace were used to analyze research trends in this area. Results: We extracted 758 articles for further analysis. China ranked first with 240 published documents, followed by the USA with 211. However, the USA ranked first regarding citation frequency with 11,380 citations, while China ranked second. The University of California Irvine and Kidney International emerged as the leading institution and journal, respectively, with the former leading in document production and citations. Although Kidney International featured fewer documents than other journals, it exhibited the highest citation count. The keywords representing the research interests mainly included: (1) gut microbiota influences the development of CKD, (2) application of probiotics in the treatment of CKD, and (3) potential mechanism of gut microbiota in CKD. Conclusion: Our analysis indicates significant advancements in understanding the association between gut microbiota and CKD. It also provides a comprehensive overview of publication trends, research hotspots, and frontiers, which may provide guidelines for future research.

Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities.

Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.

Alterations of gut microbes and their correlation with clinical features in middle and end-stages chronic kidney disease.

Gut microecosystem has been shown to play an important role in human health. In recent years, the concept of the gut-kidney axis has been proposed to explain the potential association between gut microbiota and chronic kidney disease (CKD). Here, a cohort of fecal samples collected from patients with CKD (n = 13) were involved. The composition of gut microbial communities and clinical features in CKD and end-stage renal disease (ESRD) were characterized. Our study focused on the changes in gut microbiome and the correlation with clinical features in patients with CKD and ESRD by analyzing high-throughput sequencing results of collected feces. We elucidated the alterations of gut microbiota in CKD patients at different stages of disease and initially identified the gut microbiota associated with CKD progression. We also combined correlation analysis to identify clinical features closely related to the gut microbiome. Our results offered the possibility of using non-invasive gut microbiome in the early diagnosis of course from CKD to ESRD and provide new insights into the association between clinical features and gut microbiota in CKD.

Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice.

Increasing evidence shows the essential participation of gut microbiota in human health and diseases by shaping local and systemic immunity. Despite an accumulating body of studies showing that chronic kidney disease (CKD) is closely associated with disturbances in the composition of gut microbiota, it remains unclear the importance of gut microbiota in the onset and development of CKD. For the purpose of untangling the role of gut microbiota in CKD, gut microbiota was depleted with a pool of broad-spectrum antibiotics in mice submitted to unilateral ureteral obstruction (UUO). Depletion of gut microbiota significantly decreased levels of proinflammatory cytokines and fibrosis markers, attenuating renal injury. Additionally, to study whether the pathogenic role of gut microbiota is dependent of microbial-host crosstalk, we generated mice lacking Myd88 (myeloid differentiation primary response gene 8) expression in intestinal epithelial cells (IECs) and performed UUO. The absence of Myd88 in IECs prevented a bacterial burden in mesenteric lymph nodes as observed in WT mice after UUO and led to lower expression of proinflammatory cytokines and chemokines, reducing deposition of type I collagen and, ultimately, attenuating renal damage. Therefore, our results suggest that the presence of gut microbiota is crucial for the development of CKD and may be dependent of Myd88 signaling in IECs, which appears to be essential to maturation of immune cells intimately involved in aggravation of inflammatory scenarios.

Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis.

Chronic kidney disease (CKD) represents a growing public health problem associated with loss of kidney function and cardiovascular disease (CVD), the main leading cause of morbidity and mortality in CKD. It is well established that CKD is associated with gut dysbiosis. Over the past few years, there has been a growing interest in studying the composition of the gut microbiota in patients with CKD as well as the mechanisms by which gut dysbiosis contributes to CKD progression, in order to identify possible therapeutic targets to improve the morbidity and survival in CKD. The purpose of this review is to explore the clinical evidence and the mechanisms involved in the gut-kidney crosstalk as well as the possible interventions to restore a normal balance of the gut microbiota in CKD. It is well known that the influence of the gut microbiota on the gut-kidney axis acts in a reciprocal way: on the one hand, CKD significantly modifies the composition and functions of the gut microbiota. On the other hand, gut microbiota is able to manipulate the processes leading to CKD onset and progression through inflammatory, endocrine, and neurologic pathways. Understanding the complex interaction between these two organs (gut microbiota and kidney) may provide novel nephroprotective interventions to prevent the progression of CKD by targeting the gut microbiota. The review is divided into three main sections: evidences from clinical studies about the existence of a gut microbiota dysbiosis in CKD; the complex mechanisms that explain the bidirectional relationship between CKD and gut dysbiosis; and reports regarding the effects of prebiotic, probiotic, and synbiotic supplementation to restore gut microbiota balance in CKD.

The gut-kidney-heart axis in chronic kidney disease.

The recent explosion of scientific interest in the gut microbiota has dramatically advanced our understanding of the complex pathophysiological interactions between the gut and multiple organs in health and disease. Emerging evidence has revealed that the gut microbiota is significantly altered in patients with chronic kidney disease (CKD), along with impaired intestinal barrier function. These alterations allow translocation of various gut-derived products into the systemic circulation, contributing to the development and progression of CKD and cardiovascular disease (CVD), partly mediated by chronic inflammation. Among potentially toxic gut-derived products identifiable in the systemic circulation, bacterial endotoxin and gut metabolites (e.g.,p-cresyl sulfate and trimethylamine-N-oxide) have been extensively studied for their immunostimulatory and atherogenic properties. Recent studies have also suggested similar biological properties of bacterial DNA fragments circulating in the blood of patients with CKD, even in the absence of overt infections. Despite the accumulating evidence of the gut microbiota in CKD and its therapeutic potential for CVD, the precise mechanisms for multidirectional interactions between the gut, kidney, and heart remain poorly understood. This review aims to provide recent evidence on the associations between the gut microbiota, CKD, and CVD, and summarize current understanding of the potential pathophysiological mechanisms underlying the "gut-kidney-heart" axis in CKD.

Thiol-producing microbiota of the intestine modulate oxidative stress and inflammation in Chronic Kidney Disease

Background: Inflammation and oxidative stress are among the key contributing risk factors for cardiovascular disease (CVD) in chronic kidney disease (CKD). The human gut is the home for microbiota, of which some of the gram-negative gut bacteria are known to produce low-molecular-weight thiols including glutathione (GSH). GSH is used by mammals and eukaryotic cells as a substrate of glutathione peroxidase to eliminate reactive oxygen species. This study aims to investigate whether the presence of thiol-producing gut microbiota in CKD affects the level of oxidative stress and inflammation markers. Methods: This study examined the stool sample of 41 CKD patients at three hospitals in Surabaya, Indonesia to identify the gram-negative bacteria producing thiols. Based on Ellman's assay result, the study participants were grouped into patients with thiol-producing and non-thiol-producing gram-negative gut microbiota. The markers of inflammation, high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and urinary oxidative stress marker 8-hydroxy-2' -deoxyguanosine (8-OHdG) were compared between the two groups. Results: The group with thiol-producing gut microbiota exhibited lower levels of plasma hs-CRP and urinary 8-OHdG compared to the group with non-thiol-producing gram-negative gut microbiota. In contrast, the group with thiol-producing gut microbiota has higher TAC compared to the group with non-thiol-producing gram-negative gut microbiota. Conclusion: This study emphasized that the phenotypical diversity regarding the ability to produce low-molecular-weight thiols might modulate inflammation and oxidative stress as CVD risk factors in CKD.

Dietary Components That May Influence the Disturbed Gut Microbiota in Chronic Kidney Disease.

Gut microbiota imbalance is common in patients with chronic kidney disease (CKD) and associates with factors such as increased circulating levels of gut-derived uremic toxins, inflammation, and oxidative stress, which are linked to cardiovascular disease and increased morbimortality. Different nutritional strategies have been proposed to modulate gut microbiota, and could potentially be used to reduce dysbiosis in CKD. Nutrients like proteins, fibers, probiotics, and synbiotics are important determinants of the composition of gut microbiota and specific bioactive compounds such as polyphenols present in nuts, berries. and fruits, and curcumin, may also play a key role in this regard. However, so far, there are few studies on dietary components influencing the gut microbiota in CKD, and it is therefore not possible to conclude which nutrients should be prioritized in the diet of patients with CKD. In this review, we discuss some nutrients, diet patterns and bioactive compounds that may be involved in the modulation of gut microbiota in CKD and provide the background and rationale for studies exploring whether nutritional interventions with these dietary components could be used to alleviate the gut dysbiosis in patients with CKD.

Gut microbiota and chronic kidney disease: implications for novel mechanistic insights and therapeutic strategies.

The complicated communities of microbiota colonizing the human gastrointestinal tract exert a strong function in health maintenance and disease prevention. Indeed, accumulating evidence has indicated that the intestinal microbiota plays a key role in the pathogenesis and development of chronic kidney disease (CKD). Modulation of the gut microbiome composition in CKD may contribute to the accumulation of gut-derived uremic toxins, high circulating level of lipopolysaccharides and immune deregulation, all of which play a critical role in the pathogenesis of CKD and CKD-associated complications. In this review, we discuss the recent findings on the potential impact of gut microbiota in CKD and the underlying mechanisms by which microbiota can influence kidney diseases and vice versa. Additionally, the potential efficacy of pre-, pro- and synbiotics in the restoration of healthy gut microbia is described in detail to provide future directions for research.