Abstract
Abstract: Accumulating evidences have shown the beneficial effects of astaxanthin (AST) supplementation on metabolic diseases prevention and treatment. The goal of present study was to reveal the favorable interactions among AST supplementation, gut microbiota, and kidneys in vivo, so as to attenuate kidney impairment in diabetic mice. Twenty C57BL/6J mice were assigned to a normal control group and a diabetic model group induced by a high-fat diet plus low-dose streptozotocin, and then the diabetic mice were fed with a high-fat diet without or with AST [0.01% (AST_a) or 0.02% (AST_b)] for 12 weeks. When compared to the diabetes kidney disease (DKD) group, AST supplementation delayed the renal pathological progression, reduced fasting blood glucose (AST_b: 1.53-fold, p<0.05), repressed levels of lipopolysaccharide (LPS; AST_a: 1.24-fold, p=0.008; AST_b: 1.43-fold, p<0.001) and TMAO (AST_a: 1.51-fold, p=0.001; AST_b: 1.40-fold, p=0.003), inhibited IL-6 (AST_a: 1.40-fold, p=0.004; AST_b: 1.57-fold, p=0.001) and reactive oxygen species (ROS; AST_a: 1.30-fold, p=0.004; AST_b: 1.53-fold, p<0.001), as well as regulated the Sirt1/PGC-1α/NFκB p65 signaling pathway. Moreover, the results of 16S rRNA gene-based Illumina deep sequencing in each group revealed that dietary AST supplementation also favorably modulated the gut microbiota compared with the DKD group, as evidenced by the inhibition of the harmful bacteria Clostridium_sensu_stricto_1, Romboutsia, and Coriobacteriaceae_UCG-002, and the enhancement of the probiotics such as Lachnospiraceae_NK4A136_group, Roseburia, and Ruminococcaceae. Taken together, dietary AST supplementation could protect kidneys against inflammation and oxidative stress by adjusting the gut-kidney axis in diabetic mice.
References
1 . (2021) Global Picture. IDF diabetes atlas, 10th ed [M]. Brussels, Belgium: International Diabetes Federation. Retrieved June 25th, 2022 from https://www.idf.org/news/240:diabetes-now-affects-one-in-10-adults-worldwide.html
2 Diabetic kidney disease. Nat Rev Dis. 2015;1:15018.
3 . Carotenoids in the treatment of diabetes mellitus and its complications: A mechanistic review. Biomed Pharmacother. 2017;91:31–42.
4 Roles of gut microbial metabolites in diabetic kidney disease. Front Endocrinol (Lausanne). 2021;12:636175.
5 . Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy. Biochim Biophys Acta (BBA) Mol Basis Dis. 2018;1865(7):1876–97.
6 . Intestinal microbiome and fitness in kidney disease. Nat Rev Nephrol. 2019;15(9):531–45.
7 . The gut-kidney axis in chronic renal failure: a new potential target for therapy. Hemodial In. 2017;21(3):323–33.
8 . Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp Ther Med. 2019;18(5):3461–9.
9 Trimethylamine N-oxide exacerbates renal inflammation and fibrosis in rats with diabetic kidney disease. Front Physiol. 2021;12:682482.
10 . Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp Ther Med. 2019;18(5):3461–9.
11 . The role of the gut microbiome in diabetes and obesity-related kidney disease. Int J Mol Sci. 2021;22(17):9641.
12 Astaxanthin from shrimp by-products ameliorates nephropathy in diabetic rats. Eur J Nutr. 2015;54(2):301–7.
13 . Astaxanthin promotes Nrf2/ARE signaling to alleviate renal fibronectin and collagen iv accumulation in diabetic rats. J Diabetes Res. 2018;2018:6730315.
14 Astaxanthin ameliorates experimental diabetes-induced renal oxidative stress and fibronectin by upregulating connexin43 in glomerular mesangial cells and diabetic mice. Eur J Pharmacol. 2018;5:33–43.
15 . Therapeutic uses of natural astaxanthin: an evidence-based review focused on human clinical trials. Pharmacol. Res. 2021;166.
16 . Biological and neurological activities of astaxanthin (Review). Mol Med Rep. 2022;26(4):300.
17 . Astaxanthin influence on health outcomes of adults at risk of metabolic syndrome: a systematic review and meta-analysis. Nutrients. 2022;14(10):2050.
18 . Astaxanthin supplementation mildly reduced oxidative stress and inflammation biomarkers: a systematic review and meta-analysis of randomized controlled trials. Nutr Res. 2022;99:40–50.
19 . Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab. 2008;295(6):E1323–32.
20 . Probiotics improve gut microbiota dysbiosis in obese mice fed a high-fat or high-sucrose diet. Nutrition. 2019;60:175–184.
21 . Spirulina platensis polysaccharides attenuate lipid and carbohydrate metabolism disorder in high-sucrose and high-fat diet-fed rats in association with intestinal microbiota. Food Res Int. 2021;147:110530.
22 Interpretable machine learning framework reveals robust gut microbiome features associated with type 2 diabetes. Diabetes Care. 2021;44(2):358–66.
23 . A Combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct. 2017;8(12):4644–56.
24 . Antrodin A from mycelium of Antrodia camphorata alleviates acute alcoholic liver injury and modulates intestinal flora dysbiosis in mice. J. Ethnopharmacol. 2020;254:112681.
25 Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility. J. Cell Physiol. 2019;234(5):6667–78.
26 . Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation. World J Gastroenterol. 2021;27(21):2834–49.
27 Modulatory effect of camel milk on intestinal microbiota of mice with non-alcoholic fatty liver disease. Front Nutr. 2022;9:1072133.
28 Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients. Sci Rep. 2017;7(1):1445.
29 . IL-6-induced survival of colorectal carcinoma cells is inhibited by butyrate through down-regulation of the IL-6 receptor. Carcinogenesis. 2004;25(11):2247–55.
30 Roseburia intestinalis: a beneficial gut organism from the discoveries in genus and species. Front Cell Infect Microbiol. 2021;11:757718.
31 . A purified anthraquinone-glycoside preparation from rhubarb ameliorates type 2 diabetes mellitus by modulating the gut microbiota and reducing inflammation. Front Microbiol. 2019;10:1423.
32 . Microbial composition and co-occurrence patterns in the gut microbial community of normal and obese mice in response to astaxanthin. Front Microbiol. 2021;12:671271.
33 Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice. Gut Microbes. 2020;12(1):1–19.
34 The gut microbiota is associated with the small intestinal paracellular permeability and the development of the immune system in healthy children during the first two years of life. J Transl Med. 2021;19(1):177.
35 An engineered probiotic secreting Sj16 ameliorates colitis via Ruminococcaceae/butyrate/retinoic acid axis. Bioeng Transl Med. 2021;6(3):e10219.
36 Puerarin rebuilding the mucus layer and regulating mucin-utilizing bacteria to relieve ulcerative colitis. J Agric Food Chem. 2020;68(41):11402–11.
37 Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults. Benef Microbes. 2019;10(2):121–35.
38 Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry. Gut Microbes. 2020;11(2):191–204.
39 Short-chain fatty acids ameliorate diabetic nephropathy via GPR43-mediated inhibition of oxidative stress and NF-κB signaling. Oxid Med Cell Longev. 2020;2020:4074832.
40 Oral administration of Parabacteroides distasonis antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition. Clin Exp Immunol. 2011;163(2):250–9.
41 Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–5.
42 Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci USA. 2016;113(9):E1306–15.