The Influence of the Gut Microbiota and the Gut-Peritoneal Axis on Peritoneal Dialysis: A Literature Review

Abstract

The gut microbiota corresponds to the entirety of the microbial flora present in the various sections of the intestine. It is altered in end-stage renal disease on peritoneal dialysis and may play a role in peritoneal physiology and possibly in the prognosis of peritoneal dialysis. Furthermore, until recently, the peritoneal cavity was considered a sterile environment. New studies challenge this dogma and identify a microbiome within this cavity in patients undergoing peritoneal dialysis and those with chronic kidney disease, even in the absence of a cavity breach. This review article aims to summarize the existing literature on the potential impact of the gut microbiota and the gut-peritoneal axis on the prognosis of peritoneal dialysis.

Introduction

The gut microbiota represents the entirety of the microbial flora present in various sections of the intestine. The microbiome refers to the collective genetic material associated with this microbiota[1]. The gut microbiota plays a critical role in several physiological functions, including metabolic functions, vitamin synthesis (B and K groups), maintenance of the immune system, and modulation of the autonomic nervous system[2][3][4]. Additionally, through the production of short-chain fatty acids, it contributes to colonocyte survival, regulation of gene expression, intestinal gluconeogenesis (via a cAMP-dependent mechanism), and appetite regulation[5][6]. Healthy gut microbiota also provides defense against pathogenic species through direct mechanisms (competition for resources, modification of partial oxygen pressure, production of toxins or antibiotics, detoxification of antibiotics) and indirect mechanisms (via host immune system stimulation)[5]. The gut microbiota interacts with the host’s autonomic nervous system and also plays a role in intestinal motility[7].

Peritoneal dialysis (PD) is an extracorporeal purification technique that uses the peritoneal cavity and peritoneal membrane as a filter to eliminate uremic toxins, regulate ions, and manage fluid balance. This technique requires the placement of a catheter to access the peritoneal cavity for exchange procedures. PD may be complicated by infections at the catheter exit site, subcutaneous tunnel infections, and peritonitis[8][9][10]. Other non-infectious complications are also encountered, such as peritoneal membrane dysfunction characterized by insufficient ultrafiltration[11]. The pathophysiology and susceptibility factors for these complications remain only partially understood.

The gut microbiota is altered in chronic kidney disease (CKD) and end-stage renal disease, particularly in patients undergoing PD[12][13][14].

This article aims to review the existing literature on the gut microbiota in patients undergoing peritoneal dialysis and the potential associations between alterations in the gut microbiota and certain infectious and non-infectious complications of PD.

Literature Review

1. General Overview of the Gut Microbiota

The gut microbiota encompasses the entire microbial flora present in the different sections of the intestine. It is composed of 3.8 x10¹³ microorganisms in a 70 kg adult male, corresponding to a total mass of 200 g. The concentration of microorganisms is not uniform throughout the digestive tract, with an anterograde increasing gradient from the stomach to the colon[15][16].

Defining a healthy gut microbiota in adults is challenging due to inter-individual variability. The Human Microbiome Project Consortium studied the composition of the microbiota in 242 disease-free individuals and demonstrated that, unlike highly variable microbial taxa, the metabolic pathways carried by the microbiota are stable over time and across individuals. Therefore, characterizing a healthy microbiota should focus on the functional capacities of the microbiota rather than its taxonomic composition[2][17].

2. Composition of the Microbiota

Normal Microbiota

The identification of species colonizing the gut microbiota has undergone significant advancements over the past decades with the advent of molecular biology-based technologies[18]. Rajilić-Stojanović et al. described, based on ribosomal RNA sequences, a phylogenetic framework of 1,057 species (92 Eukaryotes, 8 Archaea, and 957 Bacteria) cultured from the human gut microbiota. It was found that the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria are the most abundant and diverse. However, there are other bacterial phyla of varying abundance, such as Verrucomicrobia, Lentisphaerae, Synergistetes, Planctomycetes, Tenericutes, and the Deinococcus-Thermus group.

In addition to bacteria, fungi are also present (the mycobiota, primarily composed of Candida, Saccharomyces, Malassezia, and Cladosporium), as well as archaea, viruses, and phages[19].

Gut Microbiota in Chronic Kidney Disease

Alterations in gut microbiota composition (dysbiosis) are well documented in CKD and end-stage renal disease, with findings including increased levels of Alphaproteobacteria, Streptococcaceae, Streptococcus, Blautia, and Bacilli, and decreased levels of Prevotellaceae, Prevotella, Firmicutes, and Roseburia[20][21][22]. With moderate evidence, an increase in Klebsiella and Escherichia-Shigella has also been observed[23][24][25].

Gut Microbiota in PD

Dysbiosis is also reported in patients on PD. Stadlbauer V. et al. compared the gut microbiota of 15 hemodialysis (HD) patients, 15 peritoneal dialysis patients, and 21 controls[14]. They observed a decrease in potentially beneficial species and an increase in potentially pathogenic ones in both HD and PD patients compared to controls, with more pronounced changes in HD patients. This taxonomic alteration is associated with changes in metagenomic functionality. For example, the reduction of Roseburia intestinalis[14][26], a bacterial genus associated with numerous health benefits[27], may contribute to decreased butyrate synthesis in the intestines[14].

Consistent with findings from CKD studies, PD patients also exhibit reduced levels of Firmicutes and Actinobacteria, particularly Bifidobacteriaceae sp. and Lactobacillaceae sp., alongside an overrepresentation of Enterobacteriaceae sp.[12][13][14].

Li J. et al. demonstrated that gut microbiota diversity in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is reduced compared to non-dialyzed CKD patients and healthy controls[28]. Interestingly, they found that intestinal microbial environments were more favorable in patients on CAPD for a longer duration (60 months vs. 24-36 months), suggesting a capacity for self-regulation and microbiota adaptation over time under stable conditions. The relationship between residual renal function and protection against intestinal dysbiosis may partially be explained by a less aggressive peritoneal dialysis strategy[29].

Several studies indicate that Helicobacter pylori infection is less frequent in dialysis patients compared to those with preserved renal function[30][31]. Furthermore, CAPD patients reportedly have lower infection rates compared to HD patients[30]

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