Astaxanthin attenuated the stress-induced intestinal motility disorder via altering the gut microbiota
Abstract
Abstract: Gut microbiota and short-chain fatty acids (SCFAs) are recognized as key factors in the pathophysiology of irritable bowel syndrome. Astaxanthin is a carotenoid with strong antioxidant and anti-inflammatory activities. In this study, we examined the effects of astaxanthin on gut microbiota-, SCFAs-, and corticotropin-releasing factor (CRH)-induced intestinal hypermotility. Male Wistar rats (n=12 per group) were fed a diet with or without 0. 02% (w/w) astaxanthin for four weeks and CRH or saline was administered intravenously. The number of fecal pellets was counted 2 h after injection. Then the rats were sacrificed, and the cecal content were collected 3 h after injection. The number of feces was significantly increased by CRH injection in the control group (2.0 vs. 6.5; p=0.028), but not in the astaxanthin group (1.0 vs. 2.2; p=0.229) (n=6 per group). The cecal microbiota in the astaxanthin group was significantly altered compared with that in the control group. The concentrations of acetic acid (81.1 μmol/g vs. 103.9 μmol/g; p=0.015) and butyric acid (13.4 μmol/g vs. 39.2 μmol/g; p<0.001) in the astaxanthin group were significantly lower than that in the control group (n=12 per group). Astaxanthin attenuates CRH-induced intestinal hypermotility and alters the composition of gut microbiota and SCFAs.
References
1 . The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology. 2000;119(3):654–60.
2 . Influence of the corticotropin releasing hormone (CRH) on the brain-blood barrier permeability in cerebral ischemia in rats. J Physiol Pharmacol 2002;53(1):85–94.
3 . Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut. 1998;42(6):845–9.
4 . A role for the gut microbiota in IBS. Nat Rev Gastroenterol Hepatol. 2014;11(8):497–505.
5 Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62(1):159–76.
6 . The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133(1):24–33.
7 . Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: probiotics, prebiotics and the low FODMAP diet. Proc Nutr Soc. 2016;75(3):306–18.
8 . Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil. 2010;22(5):512–9, e114–5.
9 . Irritable bowel syndrome and gut microbiota. Curr Opin Endocrinol Diabetes Obes. 2020;27(1):28–35.
10 . Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.
11 The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study. Int J Clin Pract. 2013;67(9):895–903.
12 . Effects of dietary guidance on the symptoms, quality of life and habitual dietary intake of patients with irritable bowel syndrome. Mol Med Rep. 2013;8(3):845–52.
13 Ehealth monitoring in irritable bowel syndrome patients treated with low fermentable oligo-, di-, mono-saccharides and polyols diet. World J Gastroenterol. 2014;20(21):6680–4.
14 . Astaxanthin: A mechanistic review on its biological activities and health benefits. Pharmacol Res. 2018;136:1–20.
15 . Astaxanthin in cardiovascular health and disease. Molecules. 2012;17(2):2030–48.
16 Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta. 2001;1512(2):251–8.
17 . Astaxanthin in cardiovascular health and disease: mechanisms of action, therapeutic merits, and knowledge gaps. Food Funct. 2017;8(1):39–63.
18 . Effects of astaxanthin supplementation on oxidative stress. Int J Vitam Nutr Res. 2020;90(1–2):179–94.
19 . Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000;48(4):1150–4.
20 Effects of astaxanthin on intestinal microflora in mice fed a high-fat diet. Anti-Aging Med. 2013;10(4):77–91.
21 Astaxanthin-shifted gut microbiota is associated with inflammation and metabolic homeostasis in mice. J Nutr. 2020;150(10):2687–98.
22 . The National Academies Collection: Reports funded by National Institutes of Health. Guide for the Care and Use of Laboratory Animals. Copyright © 2011, National Academy of Sciences. Washington (DC): National Academies Press (US).
23 . Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41(4):1149–60.
24 . Long-term oral administration of cows’ milk improves insulin sensitivity in rats fed a high-sucrose diet. Br J Nutr. 2009;102(9):1324–33.
25 A preliminary study of gut dysbiosis in children with food allergy. Biosci Biotechnol Biochem. 2017;81(12):2396–9.
26 . Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010;26(19):2460–1.
27 QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–6.
28 . Effect of pH on oligosaccharide fermentation by porcine cecal digesta. Anim Sci Technol. 1998;69(2):100–7.
29 . Differential effects of carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis. Biochim Biophys Acta. 2007;1768(1):167–74.
30 . Pharmacokinetics and first-pass metabolism of astaxanthin in rats. Br J Nutr. 2011;105(2):220–7.
31 . Enhanced oral bioavailability of astaxanthin with droplet size reduction. Food Sci Technol Res. 2012;18(4):549–54.
32 Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. BioFactors (Oxford, England). 2004;20(1):49–59.
33 . Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002;7(5):290–3.
34 . Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol. 2017;312(1):G52–G62.
35 . Postinfectious irritable bowel syndrome. Gastroenterology. 2009;136(6):1979–88.
36 . Microbiota and diabetes: an evolving relationship. Gut. 2014;63(9):1513–21.
37 Dietary polyphenols promote growth of the gut bacterium akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes. 2015;64(8):2847–58.
38 . Corticotropin-releasing factor directly mediates colonic responses to stress. Am J Physiol. 1987;253(4 Pt 1):G582–6.
39 . Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation. Adv Nutr. 2017;8(3):484–94.
40 . Interdigestive myoelectric complex in germ-free rats. Digest Dis Sci. 1989;34:1180–4.
41 . Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am J Physiol Gastrointest Liver Physiol. 2001;280(3):G368–80.
42 . Short chain fatty acids and their receptors: new metabolic targets. Transl Res. 2013;161(3):131–40.
43 . The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne). 2020;11:25.
44 . Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy. Cell Physiol Biochem. 2018;49(1):190–205.
45 Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol. 2018;596(20):4923–44.
46 . Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73(4):1073–8.
47 Comparison of the fecal microbiota of two monogastric herbivorous and five omnivorous mammals. Anim Sci J. 2020;91(1):e13366.
48 . Short chain fatty acids stimulate feline colonic smooth muscle contraction. J Feline Med Surg. 2003;5(3):167–73.
49 . Contractile effect of short-chain fatty acids on the isolated colon of the rat. J Physiol. 1985;368:667–78.
50 Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol. 2003;284(5):R1269–76.
51 . Short-chain fatty acids stimulate ileal motility in humans. Gastroenterology. 1988;95(6):1496–502.
52 Depression can be prevented by astaxanthin through inhibition of hippocampal inflammation in diabetic mice. Brain Res. 2017;1657:262–8.
53 Trans-astaxanthin attenuates lipopolysaccharide-induced neuroinflammation and depressive-like behavior in mice. Brain Res. 2016;1649(Pt A):30–7.
54 . Gut-microbiota and mental health: current and future perspectives. J Pharmacol Clin Toxicol. 2014;2:1016–30.
55 Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility. Sci Rep. 2017;7(1):441.
56 . Mood and gut feelings. Brain Behav Immun. 2010;24(1):9–16.
57 . Astaxanthin: sources, extraction, stability, biological activities and its commercial applications – a review. Marine drugs. 2014;12(1):128–52.