In this study, an analysis of gut microbiome composition was performed for stool samples from subjects affected by CKD5 and matched healthy controls. It was found that the gut microbiome of patients with both CKD5-NHD and CKD5-HD demonstrated lower microbial richness as well as distinct composition compared to those of the healthy control group subjects. It was further revealed that the gut microbiome might be associated with certain enterogenous protein-binding uremic toxins. Our pilot study reported that the composition of the gut microbiome was correlated with CKD5 with and without hemodialysis.
With respect to gut the microbiome composition, the relative abundance of Lachnoclostridium (
p < 0.001) and Neisseria (
p < 0.001) was significantly higher in both the CKD5-NHD and CKD5-HD groups than in the health control group. There were some differences between our results and the discovery of Vaziri et al. [
13]. With regard to these differences, race, dietary habit, living environment and some other aspects may play critical roles. In our study, Neisseria levels were found to be elevated in the setting of esophageal inflammation, which was correlated with inflammatory disorders in pancreatic disease [
26‐
29]. As we all know, patients with CKD are under the condition of a microinflammatory state. Neisseria may aggravate this pathological condition. Several studies also demonstrated that reduced bone volume of fat diet-induced bone loss in male mice was associated with the presence of Lachnoclostridium [
30]. There were situations of dyslipidemia and mineral bone disorder (CKD-MBD) in patients with CKD5; Lachnoclostridium may be one of the culprits. Interestingly, Bifidobacterium, usually known as a kind of probiotic, was found to be significantly higher in the disease groups than in the healthy group. As we know, butyrate (BT) is one of the short chain fatty acids (SCFAs) that can maintain the health of the intestinal tract [
31]. Adequate butyrate has been proven to be critical for sustaining the health of the gut microbiome. Butyrate not only maintains the integrity of the intestinal epithelium but also provides energy for respiration of intestinal epithelial cells and regulates immune responses of the intestinal tract [
32,
33]. For instance, BT develops an antiinflammatory effect by inhibiting the recruitment and proinflammatory activity of immune cells, such as neutrophils. It could activate the differentiation of colonic Treg cells to suppress inflammation [
34]. However, when the abundance of some bacteria, such as Bifidobacterium, increased, the abundance of bacteria that generate butyrate was significantly reduced which may damage epithelial cells and deteriorate the microinflammatory state. Vaziri et al. [
35‐
37] found that ESRD patients exhibited significant expansion of bacterial families possessing urease, which resulted in the accumulation of some uremic toxins, such as IS and PCS, and the destruction of tight junctions. Alterations in the gut microbiome in both the CKD5-NHD and CKD5-HD groups may be due to intestinal microecological environmental changes. These changes may occur for several of the following reasons. ① The generally poor nutritional status of patients with injured renal function makes it difficult for a microbiome that is beneficial to the body to obtain sufficient nutritional substrates, which inhibits the growth of advantageous bacterial groups [
38]. ② Because of restraint of the advantageous bacterial groups, intestinal peristalsis slows, intestinal microvilli are injured, and the intestinal clearance ability is reduced, which provides opportunities for pathogenic bacteria to contact and adhere to mucous membranes; this possibility is also an important reason for the changes in the microbiome structure [
39]. ③ Renal dysfunction leads to the accumulation of waste material, and thus the intestinal mucosa becomes ischemic, the mucosal barrier is damaged, and the permeability of the mucous membrane increases; moreover, the growth environment for the bacteria changes due to underlying inflammation [
40]. Our results showed an increase in these three genera of bacteria, which indicates that these bacteria could be a factor that affects renal function.
The gut microbiome plays a critical role in substance metabolism and influences the essential diagnosis and treatment of various pivotal diseases, such as cancer, diabetes and CKD. In this study, our results indicated that the gut microbiome was associated with the disease indices. IS and PCS were found to have a significant positive association with Enterococcus (
p < 0.01) and Bifidobacterium (p < 0.001). It is known that IS and PCS are secreted and excreted primarily through the organic anion transporter (OAT) in renal tubules. The renal excretion function of CKD patients is impaired, resulting in a reduction in the excretion of the substance and its accumulation in the body [
41]. Simultaneously, due to the structure and function of the microbiome disturbance, overgrowth of Enterococcus, Bifidobacterium and other phenolic- and indole-producing bacteria occurred in CKD patients, resulting in increased levels of IS, PCS and other harmful metabolites and further leading to the accumulation of these two substances. Studies have shown that IS and PCS promote renal fibrosis, myocardial apoptosis, and insulin resistance and affect osteoblast function [
42‐
48]. BUN and CR are the two main indices that reflect kidney function and are filtrated by the glomerulus and partly excreted by the renal tubules. With renal (the decline of eGFR) and gut bacteria metabolism dysfunction, the concentrations of BUN and CR were increased. Due to the disordered internal environment, CKD patients usually have an intestinal microecological imbalance (i.e., proliferation of a large number of harmful bacteria and a reduction in beneficial bacteria), resulting in a state of long-term microinflammation within the body. Disordered microbiomes contribute to the state of CKD by causing the accumulation of IS, PCS, BUN, CR and other uremic toxins, thereby aggravating the illness and increasing the risk of a variety of complications, such as cardiovascular disease, and eventually increasing all-cause mortality. Therefore, modifying the gut microbiome by prebiotics may be a novel way to improve the disease state [
49,
50].