Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury

Abstract

Background: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats.Methods: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS respectively.After being built by streptozotocin (DM rats), the DM rats were administered 300mg/kg sodium butyrate for 12 weeks (DM+BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured.Results: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and bronectin and collagen expressions in renal tissues in DM+BU rats. The LC3 mRNA, LC3B / ratio and number of autophagosomes were increased in renal tissue of DM+BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM+BU rats compared with DM rats. Conclusions: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

Recent advances of gut microbiota in chronic kidney disease patients

“…Butyrate levels in serum were reduced in patients with DKD compared with patients with diabetic mellitus and healthy controls. Butyrate levels in serum were positively correlated with estimated glomerular filtration rate [65]. Treatment with butyrate could elevate butyrate levels in serum and faeces and inhibit glomerular area enlargement as well as intrarenal fibronectin and collagen IV expressions in the rats with diabetic mellitus [65].…”

“…Butyrate levels in serum were positively correlated with estimated glomerular filtration rate [65]. Treatment with butyrate could elevate butyrate levels in serum and faeces and inhibit glomerular area enlargement as well as intrarenal fibronectin and collagen IV expressions in the rats with diabetic mellitus [65]. Treatment with butyrate could increase LC3 messenger ribonucleic acid expression and LC3BII/I ratio in renal tissue of diabetic mellitus rats.…”

“…Treatment with butyrate could increase LC3 messenger ribonucleic acid expression and LC3BII/I ratio in renal tissue of diabetic mellitus rats. Intrarenal higher phospho-adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK ratio and lower phospho-mammalian target of rapamycin (p-mTOR)/mTOR ratio were demonstrated in diabetic mellitus rats with sodium butyrate compared with diabetic mellitus rats [65].…”

“…The gender and body mass index had slight influence on the gut microbiota profile but the main difference still came from the disease [64]. The latest 16S ribosomal deoxyribonucleic acid gene sequencing analysis showed dysbiosis of gut microbial was demonstrated in patients with diabetic mellitus and DKD, and relative abundance of some short chain fatty acids-producing bacteria was lowered in patients with DKD [65]. Butyrate levels in serum were reduced in patients with DKD compared with patients with diabetic mellitus and healthy controls.…”

The Preventive Effects of Fermented and Germinated Foxtail Millet Whole Grain on Kidney Damage in a Diabetic Mouse Model

“…Moreover, Cai et al . also reported that the proportion of short chain fatty acids (SCFAs)-producing bacteria in gut microbiota was decreased in DKD patients, and the oral supplement of SCFAs could improve kidney injury in the diabetic mouse model ( 19 ). These studies suggested that targeting the gut microbiota could be a novel strategy for the prevention of DKD.…”