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]. A meta-analysis showed an inverse correlation between dialysis duration (both HD and CAPD) and Helicobacter pylori infection, despite limited data specifically comparing PD to HD [32]. The causes for this reduction remain unclear but may involve the unfavorable uremic conditions for infection development.

Several factors have been implicated in intestinal dysbiosis in PD patients [33], including a phosphorus- and potassium-restricted diet that reduces fiber and symbiotic intake, uremic toxins such as urea that alter gut flora composition [34], medications like potassium binders, and finally, the PD technique itself [28].

Peritoneal dialysis has several unique features related to gut microbiota that distinguish it from other of end-stage renal disease treatment modalities. These include intraperitoneal hyperglycemia and elevated intra-abdominal pressure, which promote specific microbiota changes such as increased Enterobacteriaceae. Additionally, preservation of residual diuresis partially mitigates the deleterious effects of dysbiosis. Finally, the progressive adaptation of gut microbiota in long-term PD patients highlights a unique adjustment mechanism in this technique. These specificities strengthen the hypothesis of a close interaction between gut microbiota and peritoneal physiology in PD.

Peritoneal sclerosis is a severe complication associated with ultrafiltration failure and solute transport abnormalities. It is characterized by morphological alterations of the peritoneal membrane, including interstitial fibrosis and hyalinizing vasculopathy [35]. This condition has long been attributed to the lack of biocompatibility of the dialysis solution on the peritoneal membrane, involving factors such as high osmolarity, low pH, high glucose concentrations, advanced glycation end-products (AGEs), and glucose degradation products. These agents trigger degenerative damage to the tissue components of the peritoneal membrane and induce abnormal biological responses [36].

However, recent evidence suggests that factors independent of PD, such as uremia, may play a significant role in the pathogenesis of peritoneal sclerosis even before the initiation of PD [37]. These findings broaden our understanding of peritoneal sclerosis, suggesting that this complication could result from multiple mechanisms involving both PD-related factors and pre-existing conditions.

An emerging area of interest is the role of gut microbiota in the progression of PD-related complications. A prospective cohort study demonstrated that reduced gut microbiota diversity is associated with an increased risk of technique failure in PD patients. This association persists even after adjusting for various risk factors, including age, coronary artery disease history, diabetes, statin use, and levels of albumin, phosphorus, NT-proBNP, and glucose. Patients with lower gut microbiota diversity had significantly poorer PD technique survival compared to those with more diverse microbiota (HR, 2.038; 95% CI, 1.057–3.929; p = 0.034) [38].

Guo et al.’s study revealed a significant enrichment of Escherichia-Shigella in PD patients with reduced gut microbiota diversity compared to those with greater microbial diversity. This bacterial genus, known to include opportunistic pro-inflammatory pathogens in the intestinal tract, has been associated with elevated levels of both systemic and local pro-inflammatory cytokines [39][40]. Additionally, Escherichia-Shigella increases intestinal permeability by elevating luminal lipopolysaccharide (LPS) levels, facilitating the translocation of pathogens and harmful metabolites into systemic circulation, thereby contributing to systemic inflammation [41][42]. In PD patients, this chronic inflammation—both local and systemic—can stimulate peritoneal angiogenesis and fibrosis, exacerbating ultrafiltration failure, increasing cardiovascular event risks, and leading to discontinuation of PD therapy or even death[43][44].

The interplay between reduced microbial diversity and poor PD technique survival may, therefore, be partly explained by alterations in gut microbiota. Chronic inflammatory responses induced by the relative expansion of Escherichia-Shigella seem to play a key role in the association between gut dysbiosis and PD technique failure.

Gut dysbiosis, defined as a disruption of the normal gut microbiota composition, is increasingly recognized as a key factor in the pathogenesis of various chronic diseases, including obesity [45], insulin resistance, diabetes [46], and CKD [13]. In the context of PD, low microbial diversity has also been correlated with metabolic imbalances, such as increased triglycerides and decreased HDL-C, both of which are established cardiovascular risk factors [47][48].

Additionally, Enterobacteriaceae have been implicated in the production of uremic toxins, such as indole and p-cresol, whose elevated levels can exacerbate various diseases by inducing oxidative stress and increasing pro-inflammatory cytokine production[49][50]. Residual renal function (RRF) may play a protective role by eliminating these toxins, suggesting a potential interaction between RRF and protection against gut dysbiosis in PD patients.

Gut dysbiosis is thus a potentially important mechanism in the onset and progression of numerous diseases, including renal, metabolic, and inflammatory conditions. In PD patients, enrichment of uremic toxin-producing bacteria and depletion of short-chain fatty acid-producing bacteria can disrupt the intestinal barrier, leading to the translocation of microorganisms and their toxins into the bloodstream, thereby exacerbating peritoneal complications[51][52].

Although studies on PD patients are limited, research on hemodialysis patients has shown that altered gut microbiota is a major source of uremic toxins not cleared by the kidneys [53]. Consequently, it is plausible that the gut microbiota in PD patients is also a significant source of toxic metabolites, thereby contributing to fibrosis in organs, including the heart, kidneys, and peritoneum [35].

The accumulation of bacterial structural components, their metabolites, and uremic toxins significantly impacts fibrosis development, suggesting that uremia is a globally pro-fibrotic condition [54][55]. This condition may activate various signaling pathways promoting epithelial-to-mesenchymal transition and extracellular matrix production by mesenchymal cells [55][56][57].

In summary, gut dysbiosis associated with CKD and PD creates a vicious cycle where chronic inflammation—both intraperitoneal and systemic—and the adverse effects of glucose-based solutions contribute to peritoneal fibrosis. This complex interaction between gut microbiota and PD underscores the importance of microbiota-targeted strategies to prevent or mitigate PD-related complications [53].

PD is a home-based treatment requiring self-management and operation by patients. Consequently, cognitive function is particularly important in PD patients, as any impairment could lead to adverse events [58]. In elderly patients with cognitive disorders, the loss of executive or memory functions may result in errors in PD management, increasing the risk of PD-associated peritonitis [59]. Additionally, cognitive impairment is an independent predictor of mortality and survival in PD patients [60]. Recently, growing evidence has demonstrated a strong link between gut dysbiosis and the onset and progression of nervous system disorders, with the underlying mechanism potentially involving the «microbiota-gut-brain axis» [61]. This association has been reported in various conditions, including end-stage CKD [62]and in HD patients [63]. Very recently, this link was also confirmed in PD patients [64], suggesting a negative impact of gut dysbiosis on the progression of cognitive impairment in peritoneal dialysis patients.

Malnutrition is a common complication among dialysis patients, both in HD and PD. It results from a complex mechanism involving multiple factors, including patient-related ones such as loss of residual renal function, intestinal dysfunction [65], and inadequate nutritional intake [66], as well as PD-related factors, such as the inefficiency of dialysis, protein loss with PD effluent, and chronic microinflammation [67]. Malnutrition is also a key factor affecting the quality of life and prognosis of patients [68]. Malnourished PD patients experience higher hospitalization rates, longer hospital stays, and significantly increased risks of peritonitis and mortality [69]. Therefore, malnutrition in these patients deserves heightened attention in clinical practice. Recent studies point to a possible imbalance in the gut microbiota of malnourished PD patients [70].