TABLE 1.
Summary of current research on DN and gut microbiota
| Types | Published studies | Year | Author | Sample and methods | Subgroups | Conclusions |
|---|---|---|---|---|---|---|
| Animal studies | Gut microbiota dysbiosis‐induced activation of the intrarenal renin‐angiotensin system is involved in kidney injuries in rat diabetic nephropathy. | 2020 | Lu CC et al. |
Kidney Histology—PAS Plasma—Measurement of acetate, Measurement of circulating RAS Faeces—16S rDNA sequencing, RT‐PCR |
Healthy male Sprague–Dawley rats were divided into three groups, the latter two groups were injected with 65 mg/kg/d STZ to build DM model (1) the control group (2) DM group (3) DM + AB |
The excessive acetic acid produced by the gut microbiota may be involved in the early DN kidney damage by activating the RAS in the kidney |
| Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis. | 2020 | Hu ZB et al. |
Blood/Urine—biochemical saasy for some indicators of renal function Faeces—16 s rDNA sequencing, FMT Renal tissues—PAS, transmission electron microscopy Measurement of lipid accumulation Measurement of acetic acid concentration |
(1) WT rats treated with drinking water; (2) DM rats treated with drinking water (3) DM rats treated with an antibiotic |
Acetate‐producing bacteria in the intestine mediate the imbalance of cholesterol homeostasis by activating GPR43, resulting in tubulointerstitial damage in DN | |
| The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment. | 2020 | Li Y et al. |
Faeces—16S rRNA gene sequences, FMT, qPCR, GC–MS Serum—ELISA Urine—biochemical saasy for some indicators of renal function |
17 male SPF C57BL/6 mice were injected with 80 mg/kg/d STZ to build DM model. Then they were divided into 2 groups (1) severe proteinuria group (SP) (2) mild proteinuria group (MP) |
Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN | |
| Exploring the role of the metabolite‐sensing receptor GPR109a in diabetic nephropathy. | 2019 | Snelson M et al. |
Blood—ELISA Urine—ELISA Kidney Histology—PAS, RT‐PCR Ileum Histology—H&E, RT‐PCR |
(1) Gpr109a−/− mice treated with a control diet (2) Gpr109a−/− mice treated with a high fibre diet (3) WT mice treated with a control diet (4) WT mice treated with a high fibre diet |
This study shows that GPR109A does not play a key role in the intestinal homeostasis of T1DM or the occurrence and development of DN | |
| Gut microbiome‐derived phenyl sulphate contributes to albuminuria in diabetic kidney disease. | 2019 | Kikuchi K et al. |
Renal tissues—PAS, qPCR Blood—Untargeted metabolomics analysis, LC/MS/MS, ELISA Urine—biochemical saasy for some indicators of renal function Faeces—16S rRNA gene sequences |
SLCO4C1‐Tg rats, C57BL6 mice, KKAy mice and db/db mice which were induced by STZ 50 mg/kg/d | Gut microbiome‐derived phenyl sulphate can increase proteinuria by inducing podocyte damage in DN. Therefore, PS can become a biomarker for early diagnosis of DN and a potential therapeutic target | |
| Human studies | Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria. | 2020 | Winther SA et al. |
Faeces—16S rRNA gene sequences Serum—ultra HPLC coupled to MS/MS |
161 individuals with type 1 diabetes and 50 healthy control individuals. Individuals with type 1 diabetes were divided into(1) normoalbuminuria (<3.39 mg/mmol); (2) microalbuminuria (3.39–33.79 mg/mmol); (3) macroalbuminuria (≥33.90 mg/mmol) | In type 1 diabetic patients with macroaibuminuria, compared with those with microalbuminuria and normoalbumuria, the plasma concentrations of indoxyl sulphate, L‐citrulline and L‐kynurenine are higher, but the level of tryptophan is lower |
| Utility of plasma concentration of trimethylamine N‐oxide in predicting cardiovascular and renal complications in individuals with type 1 diabetes. | 2019 | Winther SA et al. |
Serum—concentration determination of TMAO, biochemical saasy for some indicators of renal function Urine—biochemical saasy for some indicators of renal function |
1159 individuals with type 1 diabetes | Intestinal‐derived TMAO may be a marker of renal function, and its higher concentration is associated with CVD events and poor renal prognosis | |
| Understanding the gut‐kidney axis among biopsy‐proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition. | 2019 | Tao S et al. | Faeces—16S rRNA gene sequences | 14 DNs, 14 T2DMs without renal diseases (DM), 14 healthy controls (HC) and household contacts (HH) of DM group |
DM versus HC: g_Prevotella_9 DN versus DM: the variables of g_Escherichia‐Shigella and g_Prevotella_9 |
|
| Probiotic supplementation in diabetic haemodialysis patients has beneficial metabolic effects. | 2017 | Soleimani A et al. | Serum—biomarkers of inflammation and oxidative stress |
60 diabetic patients on haemodialysis were randomly divided into 2 groups (1) treatment group: take a capsule containing the probiotics Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum for 12 weeks (2) control group: take a capsule containing placebo for 12 weeks |
Supplementation of probiotics in diabetic haemodialysis patients for 12 weeks has a beneficial effect on blood glucose homeostasis parameters and some biomarkers of inflammation and oxidative stress. | |
| Research on Chinese Medicine | Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice. | 2020 | Cai TT et al. |
Serum—biochemical saasy for some indicators of renal function, ELISA Kidney tissue—PAS, RT‐PCR Small intestine tissue—HE Faeces—16S rRNA gene sequences, FMT |
Male C57BL/KsJ diabetic db/db mice db/m mice |
After resveratrol treatment, diabetic mice have a greater change in gut microbiota than db/m mice. And the intestinal mucosal barrier is enhanced, permeability and inflammation are reduced |
| Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment. | 2020 | Singh H et al. |
Cecum tissue—16 s rDNA sequencing Urine—GC–MS |
(1) db/m mice (2) db/db mice (3) db/db + short‐acting PFD (4) db/db + long‐acting PFD (5) db/db + low‐dose CCK (6) db/db + high‐dose CCK |
PFD has a beneficial effect on db/db mice, and this effect is achieved by adjusting the abundance and diversity of gut microbiota |
Abbreviations: BCP, Bupleurum chinense DC; BHID, Bekhogainsam decoction; BPS, Bupleurum smithii var. parvifolium; CCK, cholecystokinin; CCP, Cordyceps cicadae polysaccharides; CCPH, CCP high‐dose group (300 mg/kg BW); CCPL, CCP low‐dose group (75 mg/kg BW); CCPM, CCP middle‐dose group (150 mg/kg BW); CVD, cadiovascular disease; DJP, D. loddigesii; DM + AB, diabetic rats treated with antibiotics; DM, diabetic mellitus; DMBG, dimethyl biguanide; DMBG, dimethyl biguanide group (100 mg/kg BW); DN group diabetic nephropathy group; ELISA, enzyme linked immunosorbent assay; FMT, faecal microbiota transplantation; GC‐MS, gas chromatography‐mass spectrometer; PFD, pirfenidone; PI3K/Akt, phosphatidylinositol‐3‐kinase/protein kinase B; PS, phenyl sulphate; RAS, renin‐angiotensin system; SPF, specific pathogen‐free; STZ, streptozotocin; TMAO, trimethylamine N‐oxide; WT, wild type.