Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice

Abstract

Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.

Resveratrol Improves Liver Steatosis and Insulin Resistance in Non-alcoholic Fatty Liver Disease in Association With the Gut Microbiota

“…It is generally believed that gut microbiota triggers innate and adaptive immunity and maintains the stability of the intestine ( Hooper and Macpherson, 2010 ). In previous studies about Inflammatory Bowel Disease and Diabetic Nephropathy, the transplantation of fecal microbiota from RSV gavage mice directly affected the intestinal inflammation and gut barrier of the recipient mice ( Alrafas et al, 2019 ; Cai et al, 2020 ), indicating the RSV might alter the intestinal inflammation by gut microbiota. We also observed reductions in liver inflammation and oxidative stress after RSV treatment.…”

The Osteoporosis/Microbiota Linkage: The Role of miRNA

“…Resveratrol is capable of modifying miR-21 expression in diverse cell culture models. Experiments employing the culture of U251 cells, cultured with resveratrol for 12 h, reduced miR-21 expression, and this was followed by the decrease in the generation of proinflammatory transcription factor NF-κB [ 114 ]. The reduction of miR-21 could have a beneficial effect on the progression of osteoporosis.…”

Alzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

“…Additionally, the ratio Bacteroidetes / Firmicutes is higher in db/db mice, than on C57Bl/6J mice [ 205 ]. On the other hand, family Muribaculaceae is reduced in db/db mice by 8 months of age [ 209 ], while other studies have reported that genus Rikenella (family Rikenellaceae ) is increased in db/db mice by 6 months of age [ 210 ]. It also seems that genera Paraprevotella and Alloprevotella , (family Prevotellaceae ) are increased in db/db mice by 6 months of age, while the genus Alloprevotella decreases by 8 months of age [ 209 , 211 ].…”

“…This phylum (family Prevotellaceae ) is also decreased in E4FAD and db/db mice at 8 months of age [ 209 , 211 , 248 ]. Actinobacteria (family Coriobacteriaceae ) has been reported to be increased both in APP/PS1 [ 132 ] and in db/db mice [ 205 ], while the Bacteroidaceae family seems to be less abundant in different AD and T2DM preclinical models [ 90 , 132 , 134 , 204 , 209 , 210 , 211 , 257 ]. Nevertheless, other studies have reported increases in the Bacteroidaceae family, both in AD [ 119 ] and T2DM animals [ 204 , 209 , 210 , 211 ].…”

“…Actinobacteria (family Coriobacteriaceae ) has been reported to be increased both in APP/PS1 [ 132 ] and in db/db mice [ 205 ], while the Bacteroidaceae family seems to be less abundant in different AD and T2DM preclinical models [ 90 , 132 , 134 , 204 , 209 , 210 , 211 , 257 ]. Nevertheless, other studies have reported increases in the Bacteroidaceae family, both in AD [ 119 ] and T2DM animals [ 204 , 209 , 210 , 211 ]. Phylum Firmicutes (family Ruminococcaceae, genus Ruminococcus ) has been reported to be increased in AD [ 134 ] as well as in different T2DM preclinical models [ 203 , 205 , 206 ].…”