Fructooligosaccharides Ameliorate Renal Injury and Dysfunction Through the Modulation of Gut Dysbiosis, Inhibition of Renal Inflammation, Oxidative Stress, Fibrosis, and Improve Organic Anion Transporter 3 Function in an Obese Rat Model

ScopeHigh-fat diet (HFD) consumption causes obesity and gut dysbiosis which induces kidney injury. It has been reported that prebiotics improve gut dysbiosis and insulin sensitivity and decelerate the progression of kidney disease. This study investigates the impact of fructooligosaccharides (FOS) on renoprotection and the prevention of gut dysbiosis and intestinal barrier injury in obese rats.Methods and resultsWistar rats are treated with HFD for 16 weeks. Then, the HFD fed rats (HF) are given FOS 1 g day-1 (HFFOS1), 2 g day-1 (HFFOS2), or metformin 30 mg kg-1 day-1 (HFMET), by intragastric feeding for 8 weeks. Blood, urine, feces, kidney, and intestine are collected to determine the metabolic changes, gut dysbiosis, and the expression of proteins involved in kidney and intestinal injury. FOS can attenuate insulin resistance and hypercholesterolemia concomitant with the inhibition of renal inflammation, oxidative stress, fibrosis, and apoptosis, which are related to the deceleration of the overexpression of renal Toll-like receptor 4 (TLR4) and NADPH oxidase (NOX4). Moreover, FOS shows a greater efficacy than metformin in the reduction of the intestinal injury and loss of tight junction proteins induced by HFD.ConclusionFOS may be used as a supplement for therapeutic purposes in an obese condition to improve intestinal integrity and prevent renal complications. FOS show renoprotective effects by reducing renal inflammation, oxidative stress, fibrosis, and apoptosis, attenuating the impaired renal signaling associated with organic anion transporter 3 (Oat3) function. The effects of FOS are potentially due to the bifidogenic effects in improving gut dysbiosis and the attenuation of gut leakage which could inhibit various inflammation responses in the renal cells. image