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. 2023 Oct 31;29:148. doi: 10.1186/s10020-023-00745-z

Table 1.

A summary of current studies about the impact of gut microbial metabolites in DKD in vivo and in vitro

Metabolites Human/animal/cell type species Conclusions Reference and year
SCFAs (acetate, butyrate, propionate) DKD patients The levels of serum and fecal SCFAs (especially in fecal) are lowered, and which are negatively correlated with renal function Zhong et al. (2021)
SCFAs (acetate, butyrate, propionate) C57BL/6 mice, T2D Mouse model induced by HFD and STZ, glomerular mesangial cells SCFAs, especially butyrate, improved T2D-induced kidney damages including reduction of proteinuria, serum creatinine, urea nitrogen, and cystatin C, inhibition of mesangial matrix accumulation and renal fibrosis via GPR43-mediated inhibition of oxidative stress and NF-κB signaling, Huang et al. (2020)
High-fiber diet, SCFAs (acetate, butyrate, propionate) C57BL/6, Gpr43−/− and Gpr109A−/− mice; Mouse kidney tubular epithelial cells and podocytes SCFAs can ameliorate renal damages, inhibit the expression of fibrosis-related genes (TGF-β and fibronectin), and decrease the inflammation in renal tubular cells and podocytes exposed to hyperglycemic by activating GPR43 or GPR109A receptors Li et al. (2020)
NaB Juvenile Sprague Dawley rats NaB treatment can improve the renal function and alleviate the pathological injury, fibrosis, apoptosis and DNA damage in the diabetic kidney Khan et al. (2014)
NaB C57BL/6(Nrf2+/+) and Nrf2−/− mice NaB treatment protect against DN by activating Nrf2 possibly via inhibition of HDAC activity DDong et al. (2017)
NaB db/db mice, NRK-52E cells Sodium butyrate plays an anti-apoptotic effect in the kidney of db/db mice and HG-induced NRK-52E cells by inhibiting expression of HDAC2 Du et al. (2020)
SCFAs (acetate, butyrate, propionate) C57BL/6 mice, Mouse glomerular mesangial cells SCFAs, especially acetate and butyrate, significantly inhibit proliferation of GMCs,production of ROS and MDA, expression of ICAM-1 and proinflammatory cytokine(MCP-1and IL-1β) induced by high glucose and LPS Huang et al. (2017a, b)
TMAO Sprague Dawley rats TMAO treatment not only aggravates the renal dysfunction and fibrosis, but also accelerates renal inflammation by activating NLRP3 inflammasome and releasing IL-1β and IL-18 Fang et al.(2021a, b)
Bile acids (FXR/TGR5 Dual Agonist) DBA/2 J mice, C57BL/6 J mice, db/db mice INT-767, as a semisynthetic bile acid derivative, can reduce proteinuria and relieve podocyte injury, mesangial expansion, and tubulointerstitial fibrosis via multiple pathways and targets Wang et al. (2018)
UDCA db/db mice, podocyte UDCA exerts renoprotective effects by reducing the occurrence of oxidative stress and exhibits renal protection in vivo and in vitro Cao et al.(2016a, b)
UDCA and 4-PBA db/db mice, podocyte UDCA Reduces renal pathological injury and apoptosis of podocytes by inhibiting activation of caspase-3 and caspase-12 and restoring autophagy in vivo and vitro Cao et al. (2016a, b)
TUDCA db/db mice, eNOS−/− mice, Podocytes, Human proximal tubular epithelial cells TUDCA ameliorates tubular damage by inducing expression of FXR-dependent genes (SOCS3 and DDAH1) in tubular cells,db/db and eNOS−/− mice Marquardt et al. (2017)
TUDCA db/db mice TUDCA reduces blood glucose, albuminuria and renal histopathology by inhibiting ER stress in the kidneys of diabetic db/db mice Zhang et al. (2016)
IS C57BL/6 mice, FVB/N mice, human kidney autopsy podocyte IS promotes glomerular and podocyte injury including altered cell morphology, decreased expression of podocyte differentiation markers, and a proinflammatory state by activating podocyte AhR Ichii et al. (2014)
IS T2D patients Level of serum IS is negatively correlated with renal function Atoh et al. (2009)
PS C57BL6 mice,db/db mice, KKAy mice, diabetes patients The level of plasma PS is not only significantly correlated with proteinuria/creatinine and estimated glomerular filtration rate in diabetic patients, but also can predict the deterioration of ACR in DKD patients in 2 years Kikuchi et al. (2019)

SCFA short-chain fatty acids; HFD high fat diet; STZ streptozocin; GPR43 G-protein-coupled receptor 43; NF-κB nuclear factor kappa B; GPR109A G-protein-coupled receptor 109A; TGF-β transforming growth factor-β; NaB sodium butyrate; HDAC histone deacetylase; NRF2 nuclear factor erythroid 2-related factor 2; HG high glucose; NRK-52E normal rat kidney tubular epithelial cells; GMCs glomerular mesangial cells; ROS reactive oxygen species; MDA malondialdehyde; ICAM-1 intercellular cell adhesion molecule-1; MCP-1 monocyte chemotactic protein-1; IL-1βinterleukin-1 β; LPS lipopolysaccharide; TMAO Trimethylamine N-oxide; NLRP3 nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome; IL-18 interleukin-18; FXR farnesoid X receptor; TGR5 G-protein-coupled BA receptor 1; UDCA Ursodeoxycholic acid; 4-PBA 4-phenylbutyrate; TUDCA tauroursodeoxycholic acid; eNOS endothelial nitric oxide synthase; SOCS3 suppressor of cytokine signaling 3; DDAH1 dimethylarginine dimethylaminohydrolase 1; IS Indoxyl sulfate; AhR aryl-hydrocarbon receptor; PS phenyl sulfate; ACR albumin to creatinine ratio