Alterations to the Gut Microbiota and Their Correlation With Inflammatory Factors in Chronic Kidney Disease

Abstract

Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to complications and disease progression in chronic kidney disease (CKD). Nevertheless, the effect of gut dysbiosis on the pathogenesis and/or production of inflammatory factors in CKD has not been extensively studied to date. In the present study, we conducted 16S ribosomal DNA pyrosequencing using fecal microbiota samples and analyzed the production of serum inflammatory factors in 50 patients with CKD and 22 healthy control (HC) subjects. The results revealed that compared to the HC subjects, patients with CKD exhibited a significant reduction in the richness and structure of their fecal microbiota. At the phylum level, compared to the HC group, patients with CKD also presented reduced abundance of Actinobacteria but increased abundance of Verrucomicrobia. Moreover, the genera Lactobacillus, Clostridium IV, Paraprevotella, Clostridium sensu stricto, Desulfovibrio , and Alloprevotella were enriched in the fecal samples of patients with CKD, while Akkermansia and Parasutterella were enriched in those of the HC subjects. The abundance of Akkermansia in the CKD group was significantly lower than that in the HC group (3.08 vs. 0.67%); this decrease in the abundance of Akkermansia , an important probiotic, in patients with CKD is a striking discovery as it has not been previously reported. Finally, we analyzed whether these changes to the fecal microbiota correlated with CKD clinical characteristics and/or the production of known inflammatory factors. Altered levels of the microbiota genera Parasutterella, Lactobacillus, Paraprevotella, Clostridium sensu stricto , and Desulfovibrio were shown to be correlated with CKD disease-severity indicators, including the estimated glomerular filtration rate. Most notably, Akkermansia was significantly negatively correlated with the production of interleukin-10. The results of the present study suggest that microbiota dysbiosis may promote chronic systemic inflammation in CKD. Furthermore, they support that modifying the gut microbiota, especially Akkermansia , may be a promising potential therapeutic strategy to attenuate the progression of, and/or systemic inflammation in, CKD.

Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients

“…Bacteroides is one of the most abundant bacterial genera in the gut of healthy adults and patients with CKD [60]. Enrichment of aerobic bacteria in the colon of patients with CKD has been frequently reported [23,29,30,61,62], and was also confirmed in the present study (i.e., Enterobacteriaceae and E. coli).…”

“…In a previous sequence-based comparison of the gut microbiota between patients with CKD stages 1 to 5 and non-CKD controls; however, higher Lactobacillus spp. levels in CKD were found [60]. Another health-promoting bacterial species is Akkermansia muciniphila, an essential propionate-generating and mucus-degrading species that is beneficial through the production of energy from mucus degradation and as such supporting the growth of butyrate-producing bacteria [60,[67][68][69].…”

“…Another health-promoting bacterial species is Akkermansia muciniphila, an essential propionate-generating and mucus-degrading species that is beneficial through the production of energy from mucus degradation and as such supporting the growth of butyrate-producing bacteria [60,[67][68][69]. A sequencing study comparing CKD patients with controls reported a strong negative correlation with CKD and a reduction of the genus Akkermansia, of which the species A. muciniphila is the only human representative [60]. These findings are in contrast to the present study with only a lower abundance of A. muciniphila in the CKD group versus the dialysis group, and no inverse correlation with loss of kidney function.…”

High-throughput sequencing analysis of intestinal flora changes in ESRD and CKD patients

“…A Chinese study observed no significant differences in intestinal flora diversity between CKD patients and healthy control groups, suggesting that bacterial diversity was not seriously damaged in this population [14]. Microbiota dysbiosis, which was differed between modes of dialysis, was considered a main risk factor in promoting chronic systemic inflammation in CKD patients [22]. Besides dialysis modes, age and dialysis vintage also contributed to the microbiome diversity [20].…”

Differences in Gut Microbiota Profiles and Functions Between End-stage Renal Disease and Healthy Populations 

“…In theory, the in ux of uremic toxins and urea into the gastrointestinal lumen provoke the overgrowth of bacteria that produce urease, uricase, indole, and p-cresol forming enzymes, generating a vicious cycle of in ammation and oxidative stress in ESRD patients [22]. Increased abundance of phylum Verrucomicrobia [63] and family Enterobacteriaceae [13,64] in CKD patients has also been found. However, Actinobacteria phylum and Akkermansia genera are reduced in CKD patients [63] compared to ESRD patients.…”