Table 2. Summary of the Current Literature Supporting Gut Dysbiosis in Patients with Chronic Kidney Disease^a.

subjects	alteration of gut microbiota	main findings	ref
immunoglobulin (Ig) A nephropathy patients	• elevation of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae, Streptococcaeae, Sutterellaceae, and Enterobacteriaceae	• IgAN patients had an altered fecal microbiota	(45)
	• reduction of Bifidobacterium and species of Clostridium, Enterococcus and Lactobacillus
HD patients	• elevation of enterobacteria (Klebsiella and Escherichia coli), enterococci, and Clostridium perfringens	• an overgrowth of aerobes of the fecal microbiota in HD patients is responsible for a high accumulation of p-cresol and indole	(81)
	• reduction of bifidobacteria
CKD stage 2–3 patients	• elevation of the phyla Actinobacteria and Proteobacteria	• lower intestinal flora diversity and abundances	(49)
	• elevation of the genera Bacteroides, Escherichia, Ruminococcus, Blautia, Enterococcus, Clostridium, Eubacterium, Klebsiella, Sarcina, Eggerthella, Turicibacter, Bilophila and Pseudoramibacter	• Ruminococcus and Roseburia displayed the highest diagnostic values for distinguishing CKD patients from healthy controls
	• reduction of the genera Roseburia, Prevotella, Faecalibacterium, Megamonas, Coprococcus, Burkholderia, Dialister, Lachnospira, Streptococcus, Megasphaera, Sutterella, Collinsella, Stenotrophomonas, Haemophilus, Odoribacter, Butyricimonas, Acidaminococcus, and Granulicatella
ESRD patients	• elevation of Bacteroides, Escherichia/Shigella, Subdoligranulum, Fusobacterium	• this reduction in beneficial bacteria may play an important role in the pathogenic processes of CKD	(106)
	• reduction of Prevotella, Roseburia, Faecalibacterium, Clostridium, Coprococcus, Dorea.
HD patients and nondialyzed CKD patients	• elevation of the phyla Bacteroidetes and Proteobacteria	• the differential gut microbiota has the potential to guide noninvasive diagnosis and targeted interventions	(119)
	• elevation of the genera Bacteroides, Escherichia Shigella, Parabacteroides, Ruminococcus gnavus group, Ruminococcus torques group, Weissella, Flavonifractor, Ruminiclostridium 5, Sellimonas, Erysipelatoclostridium, Eggerthella, and Clostridium innocuum group	• Holdemanella, Megamonas, and Prevotella2 were exhibited the highest abundance, whereas Dielma and Scardovia were absent in healthy controls; these genera could be an indicator of the progression of CKD and HD
	• reduction of the phyla Firmicutes
	• reduction of the genera Dialister, Eubacterium rectale group, Carnobacterium, Lachnospira, Subdoligranulum, Eubacterium coprostanoligenes group, Coprococcus 2, Roseburia, RuminococcaceaeUCG 009, Ruminococcaceae NK4A214 group, Lachnospiraceae FCS020 group, Ruminococcus1, Romboutsia, Butyricicoccus, Collinsella, RuminococcaceaeUCG 003, Eubacterium hallii group, Tyzzerella3, and LachnospiraceaeUCG 001
ESRD patients	• elevation of the families Enterobacteriaceae, Halomonadaceae, Moraxellaceae, Polyangiaceae, Pseudomonadaceae, and genera Brachybacterium, Catenibacterium, Nesterenkonia, and Thiothrix were markedly increased in patients with ESRD	• ESRD significantly modifies the composition of gut microbiome in humans; uremia and the strict dietary restrictions must have contributed to the observed changes in their microbial flora	(111)
	• reduction of the families Sutterellaceae, Bacteroidaceae, and Lactobacillaceae
CKD and ESRD patients	• at the phylum level, the relative abundance of Proteobacteria was enriched in the ESRD group, whereas Euryarchaeota was more abundant in the healthy control group	• a decrease in 14 SCFA-producing bacteria in the CKD group, including R. bromii, R. callidus, R. hominis, E. rectale, F. prausnitzii, C. comes, C. eutactus, C. sporogenes, S. variabile, D. succinatiphilus, B. adolescentis, L. crispatus, A. indistinctus, and A. inops, which could promote CKD progression by impairing intestinal barrier function and stimulating excessive inflammation	(7)
	• at the family level, Veillonellaceae, Lactobacillaceae, and Eubacteriaceae significantly decreased, but Enterobacteriaceae gradually increased in the ESRD group. Rikenellaceae, Lactobacillaceae, and Clostridiaceae decreased in the moderate CKD group, and Selenomonadaceae increased in the mild CKD group	• the distinct changes in gut microbiota were associated with alterations in the metabolic functions of arginine and proline, arachidonic acid, and glutathione, as well as in the biosynthesis pathways of ubiquinone and other terpenoid-quinone compounds during CKD progression
	• at the genus level, Roseburia, Faecalibacterium, Eubacterium rectale, Eubacterium, and Ruminococcus considerably decreased in the moderate CKD and ESRD groups, whereas Flavonifractor and Citrobacter increased in these groups	• the disrupted microbiota in relation to CKD severity may be implicated in an imbalanced toxic and pro-oxidant metabolism within both the gut and host, ultimately accelerating the CKD progression, which may represent a valuable early diagnostic and therapeutic target for CKD
	• Species varied across CKD progress:
	Four species increased (Citrobacter freundii, Citrobacter werkmanii, Flavonifractor plautii, and Anaerostipes caccae) during CKD progression
	Fourteen species decreased (Methanobrevibacter smithii, Coprococcus comes, Coprococcus eutactus, Clostridium sporogenes, Ruminococcus callidus, Ruminococcus bromii, Roseburia hominis, Faecalibacterium prausnitzii, Veillonella parvula, Megasphaera elsdenii, Dialister succinatiphilus, Acidaminococcus intestini, Faecalicoccus pleomorphus, and Subdoligranulum variabile) during CKD progression
	• Species varied in only a specific CKD group:
	Megasphaera micronuciformis level increased in the mild CKD group
	Alistipes indistinctus, Alistipes inops, and Bacteroides uniformis levels decreased in the moderate CKD group
	Turicibacter sanguinis level increased, but the Streptococcus mutans, Bifidobacterium adolescentis, and Lactobacillus crispatus levels decreased in the ESRD group
ESRD patients	• the most enriched species in patients included Eggerthella lenta, Flavonifractor spp. (mainly F. plautii), Alistipes spp. (mainly A. finegoldii and A. shahii), Ruminococcus spp. and Fusobacterium spp.	• over a half of the species were significantly altered in ESRD patients, suggesting ESRD strongly affects the microbiome	(120)
	• depleted species included Prevotella spp. (mainly P. copri), Clostridium spp. and several butyrate producers (Roseburia spp., Faecalibacterium prausnitzii and Eubacterium rectale)	• the enrichment of uremic toxins in patients with ESRD is associated with gut microbiome-mediated aromatic amino acids degradation and microbial secondary bile acids biosynthesis
ESRD patients	• elevation of Alteromonadaceae, Clostridiaceae, Dermabacteraceae, Enterobacteriaceae, Halomonadaceae, Polyangiaceae, Moraxellaceae, Methylococcaceae, Micrococcaceae, Cellulomonadaceae, Pseudomonadaceae, Xanthomonadaceae, Verrucomicrobiaceae	• patients with ESRD exhibited significant expansion of bacteria possessing urease, uricase, and indole- and p-cresol-forming enzymes and reduced bacterial families possessing butyrate-forming enzymes	(9)
	• reduction of Lactobacillaceae, and Prevotellaceae.
ESRD patients	• four decreased (Prevotella sp. 885, Weissella confuse, Roseburia faecis, and Bacteroides eggerthii) and three elevated species (Alloscardovia omnicolens, Merdibacter massiliensis, and Clostridium glycyrrhizinilyticum) were altered across non-CKD, early to advanced stages	• these results implicate specific gut microorganisms as useful biomarkers for early CKD diagnosis and prognosis monitoring	(118)
	• Cetobacterium somerae (mild CKD), Candidatus Stoquefichus sp. KLE1796 (mild CKD), Fusobacterium mortiferum (moderate CKD), Bariatricus massiliensis (moderate CKD), Bacteroides stercorirosoris (moderate CKD), and Merdimonas faecis (advanced CKD) were altered only in particular stages
CKD stage 4–5 patients	• elevation of Proteobacteria, Enterobacteriaceae, Corynebacteriaceae, Enterococcus	• CKD patients have increased plasma TMAO levels due to contributions from impaired renal functions and gut microbiota dysbiosis	(8)
	• reduction of Ruminococcaceae, Prevotella, Roseburia, Coprococcus
CKD stage 2–4 cats	• reduction of Holdemania, Adlercreutzia, Eubacterium, Slackia, and Mogibacterium	• decreased fecal microbiome diversity and richness are associated with CKD in cats	(121)

^aHD, hemodialysis; ESRD, end stage renal disease; CKD, chronic kidney disease; TMAO, trimethylamine-N-oxide.