Table 1 A summary of current studies about the impact of gut microbial metabolites in DKD in vivo and in vitro

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)