The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

Table 1

The related mechanism in the relationship between gut microbiota and kidney diseases.

Kidney diseases	Related mechanism	Conclusions	References
LN	Molecular mimicry	In susceptible individuals, symbiotic bacterial antigens cross-react with human DNA to activate the immune system and destroy self-tolerance, which is positively correlated with SLE activity and LN.	[70, 71]
	Treg/Th17 imbalance	Treg/Th17 imbalance can trigger immune responses and promote the production of SLE autoantibodies.	[40, 42]
	↑TLR7 and TLR9	An increase of TLR7 and TLR9 can contribute to alterations of proinflammatory cytokines in lupus patients.	[64, 65]
	Antinuclear antibodies	Mice with reduced gut bacteria developed nephritis more slowly and had lower levels of circulating antinuclear antibodies (ANAs) compared to the control group.	[67, 69]
		Germ-free lymphotoxin-deficient animals monocolonized with SFB produced more ANAs than lymphotoxin-deficient controls monocolonized with E. coli.	[68]
CKD	Endoxin	Endotoxemia can lead to systemic inflammation, oxidative stress, cardiac injury, and atherosclerosis.	[52]
	Uremic toxins (TMAO, IS, and PCS)	Uremic toxins cause inflammation and tubulointerstitial damage and promote ROS production, tubulointerstitial damage, epithelial cytotoxicity of proximal renal tubules, and progressive podocyte and glomerular damage.	[51, 96, 97]
	SCFAs	Gut-derived SCFAs trigger hypertension through Olfr78 in the peripheral blood vessels and renal afferent arterioles, which in turn leads to renin secretion and regulation of peripheral resistance.	[23, 84, 101]
DN	Insulin resistance	Intestinal dysbiosis is involved in insulin resistance and apoptosis of islet cells in diabetes.	[7, 10, 11, 116, 118]
	Activation of the RAS	Ang II accelerates the progression of DN by inducing renal vasoconstriction, promoting renal cell morphology, extracellular matrix deposition, inflammatory cytokine secretion, and fibro-promoting chemokines.	[125, 126]
	Uremic toxin	Phenyl sulfate can cause proteinuria and podocyte injury in diabetic mice. Inhibition of phenyl sulfate can reduce proteinuria in diabetic mice.	[122]
IRI	Bone marrow monocytes and renal resident macrophages	Applying antibiotics can diminish the gut microbiome and protect against kidney IRI profoundly by reducing the maturation status of bone marrow monocytes and F4/80^+ renal resident macrophages.	[138]
IgAN	TGF-β, BAFF, and APRIL	Intestinal dysbiosis and chronic bacterial infections could stimulate epithelial cells to produce BAFF and APRIL which could promote excessive production of IgA.	[140, 144–147]
	Endoxin (LPS)	LPS is involved in the presence of important features of IgAN pathogenesis: hyperproduction and hypogalactosylation of IgA1.	[151]