便秘(constipation)是一种临床常见疾病,发病率逐年上升。大量研究证明补充特定益生菌可以缓解便秘。因此该研究选取3株不同来源的双歧杆菌,研究其对便秘的缓解作用并进一步探究其可能的缓解途径。使用双歧杆菌干预小鼠4周,期间用盐酸洛哌丁胺处理3周构建便秘小鼠模型,通过对小鼠便秘相关指标的检测,确定两歧双歧杆菌CCFM1167对便秘具有较好的缓解作用,并进一步对小鼠便秘相关胃肠调节肽、炎症相关指标和短链脂肪酸进行检测以及相关性分析。结果表明两歧双歧杆菌CCFM1167提升便秘小鼠肠道中短链脂肪酸尤其是乙酸的含量,上调小鼠白细胞介素10及调节性T细胞含量,减轻肠道炎症。推测CCFM1167通过提高便秘小鼠肠道内乙酸的含量,缓解小鼠由洛哌丁胺导致的炎症,提高粪便含水量进而缓解便秘。
Constipation is a common clinical disease whose incidence is increasing year by year. Numerous studies have shown that constipation could be relieved via probiotics intervention. In this study, the relieving effects of three Bifidobacterium strains from different sources were investigated and their possible mitigation pathways were further explored. The mice were intervened with Bifidobacterium strains for four weeks. During this period, a mouse model of constipation was established by treating with loperamide hydrochloride for three weeks. Through the detection of constipation-related indexes of mice, it was determined that Bifidobacterium bifidum CCFM1167 had a better alleviating effect on constipation than other two strains. Furthermore, the constipation-related gastrointestinal regulatory peptides, inflammation-related indicators and short-chain fatty acids (SCFAs) of mice were detected and the correlation between them was further analyzed. The results showed that CCFM1167 increased the content of SCFAs, especially acetate, in feces. Meanwhile, CCFM1167 was able to relieve intestinal inflammation by up-regulating the levels of IL-10 and regulatory T cells. And the reduction of intestinal inflammation was positively correlated with the relief of constipation. It is speculated that CCFM1167 alleviated the loperamide-induced inflammation by increasing the intestinal acetate level, and combined with increasing the water content of feces to relieve constipation-related symptoms.
[1] AZIZ I, WHITEHEAD W E, PALSSON O S, et al.An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation[J].Expert Review of Gastroenterology and Hepatology, 2020, 14(1):39-46.
[2] GHOSHAL U C.Chronic constipation in Rome IV era:The Indian perspective[J].Indian Journal of Gastroenterology, 2017, 36(3):163-173.
[3] LEMBCKE B.Chronic constipation—What to do?[J].Praxis, 1994, 83(42):1 190-1 194.
[4] SCHOULTZ I, KEITA Å V.The intestinal barrier and current techniques for the assessment of gut permeability[J].Cells, 2020, 9(8):1909.
[5] TAJIK N, FRECH M, SCHULZ O, et al.Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis[J].Nature Communications, 2020, 11(1):1995.
[6] KHALIF I L, QUIGLEY E M, KONOVITCH E A, et al.Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation[J].Digestive & Liver Disease, 2005, 37(11):838-849.
[7] JOHANSON J F, MORTON D, GEENEN J, et al.Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation[J].American Journal of Gastroenterology, 2008, 103(1):170-177.
[8] 王爱丽, 武庆斌, 孙庆林.肠道菌群与肠道黏膜免疫系统的相互作用机制[J].中国微生态学杂志, 2009, 21(4):382-385.
WANG A L, WU Q B, SUN Q L.Interaction mechanism between intestinal flora and intestinal mucosal immune system[J].Chinese Journal of Microecology, 2009, 21(4):382-385.
[9] 刘揆亮, 吕愈敏, 顾芳. 益生菌在炎症性肠病中的应用[J]. 世界华人消化杂志, 2010, 18(36):3 891-3 895.
LIU K L, LYU Y M, GU F. Role of probiotics in the management of inflammatory bowel disease[J]. World Chinese Journal of Digestology, 2010, 18(36):3 891-3 895.
[10] BAZZOCCHI G, GIOVANNINI T, GIUSSANI C, et al.Effect of a new synbiotic supplement on symptoms, stool consistency, intestinal transit time and gut microbiota in patients with severe functional constipation:A pilot randomized double-blind, controlled trial[J].Techniques in Coloproctology, 2014, 18(10):945-953.
[11] 李鑫萍, 王琳琳, 赵建新, 等.两歧双歧杆菌FGSYC45M3缓解泻剂结肠及其作用机制分析[J].食品与发酵工业, 2021, 47(22):42-48.
LI X P,WANG L L,ZHAO J X, et al.Analysis of the effects on cathartic colon alleviation by Bifidobacterium bifidum FGSYC45M3 and its mechanism[J].Food and Fermentation Industries, 2021, 47(22):42-48.
[12] 毛丙永. 功能性低聚糖对肠道细菌的影响及机制[D].无锡:江南大学, 2015.
MAO B Y.Effects of functional oligosaccharides on the gut bacteria and the mechanism[D].Wuxi:Jiangnan University, 2015.
[13] LACY B E, MEARIN F, CHANG L, et al.Bowel disorders[J].Gastroenterology, 2016, 150(6):1 393-1 407.
[14] YAMADA K, ONODA Y.Comparison of the effects of T-1815, yohimbine and naloxone on mouse colonic propulsion[J].Journal of Smooth Muscle Research, 1993, 29(2):47-53.
[15] MORI T, SHIBASAKI Y, MATSUMOTO K, et al.Mechanisms that underlie μ-opioid receptor agonist-induced constipation:Differential involvement of μ-opioid receptor sites and responsible regions[J].The Journal of Pharmacology & Experimental Therapeutics, 2013, 347(1):91-99.
[16] BLACK C J, FORD A C.Chronic idiopathic constipation in adults:Epidemiology, pathophysiology, diagnosis and clinical management[J].The Medical Journal of Australia, 2018, 209(2):86-91.
[17] SHIMOYAMA T, TAKAHASHI R, KIMURA M, et al.Study of the mechanisms of a Japanese traditional fermented medicine in the improvement of constipation[J].Journal of Gastroenterology & Hepatology, 2015, 30(S1):53-59.
[18] NIWA T, TAKASHI M, HOSHI S, et al.Effect of dietary fiber on morphine-induced constipation in rats(food & nutrition science)[J].Bioscience Biotechnology & Biochemistry, 2002, 66(6):1 233-1 240.
[19] TEDELIND S, WESTBERG F, KJERRULF M, et al.Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease[J].World Journal of Gastroenterology, 2007, 13(20):2 826-2 832.
[20] OJO B, EL-RASSI G D, PAYTON M E, et al.Mango supplementation modulates gut microbial dysbiosis and short-chain fatty acid production independent of body weight reduction in C57BL/6 mice fed a high-fat diet[J].Journal of Nutrition, 2016, 146(8):1 483-1 491.
[21] DEN BESTEN G, VAN EUNEN K, GROEN A K, et al.The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism[J].Journal of Lipid Research, 2013, 54(9):2 325-2 340.
[22] MAYNE C G, WILLIAMS C B.Induced and natural regulatory T cells in the development of inflammatory bowel disease[J].Inflammatory Bowel Diseases, 2013, 19(8):1 772-1 788.
[23] FIORUCCI S, BIAGIOLI M, ZAMPELLA A, et al.Bile acids activated receptors regulate innate immunity[J].Frontiers in Immunology, 2018, 9:1853.
[24] 白云. 表达鼠源GLP-2嗜酸乳杆菌的构建及其对IBD模型小鼠的影响[D].长春:吉林农业大学, 2015.
BAI Y.Construction of recombined Lactobacillus acidophilus in which mouse GLP-2 expressed[D].Changchun:Jilin Agricultural University, 2015.
