Effect of fucoidan on gut microbiota and its clinical efficacy in Helicobacter pylori eradication: A randomized controlled trial

Abstract

Objective: To assess the clinical efficacy of fucoidan-assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota.

Methods: An open-label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment.

Results: After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone.

Conclusions: Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan-assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication.

Keywords

16s rDNA sequencing / fucoidan / gastrointestinal microbiome / Helicobacter pylori / standard quadruple therapy

References

[1] LiuWZ,XieY, LuH, et al; Chinese Society of Gastroenterology, Chinese Study Group on Helicobacter pylori and Peptic Ulcer. Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection. Helicobacter. 2018;23(2):e12475.

[2] MalfertheinerP,MegraudF, O’MorainCA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6-30.

[3] YangH,LiuYQ, CaiR,LiY, GuB. A narrative review of relationship between gut microbiota and neuropsychiatric disorders: mechanisms and clinical application of probiotics and prebiotics. Ann Palliat Med. 2021;10(2):2304-2313.

[4] SugawaraI,Ishizaka S. Polysaccharides with sulfate groups are human T-cell mitogens and murine polyclonal B-cell activators (PBAs). I. Fucoidan and heparin. Cell Immunol. 1982;74(1):162-171.

[5] ShibataH,Kimura-Takagi I,NagaokaM, et al. Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells. J Nutr Sci Vitaminol (Tokyo). 1999;45(3):325-336.

[6] ZhangXL,JiangC, XuS,TianZB. Regulatory effect of fucoidan on intestinal flora disturbance in mice after Helicobacter pylori infection. J Precis Med. 2021;36(3):222-226, 230. [in Chinese].

[7] MoraisCA,de Rosso VV,EstadellaD,PisaniLP. Anthocyanins as inflammatory modulators and the role of the gut microbiota. J Nutr Biochem. 2016;33:1-7.

[8] ChuaEG,Verbrugghe P,PerkinsTT,TayCY. Fucoidans disrupt adherence of Helicobacter pylori to AGS cells in vitro. Evid Based Complement Alternat Med. 2015;2015:120981.

[9] ChenLY,XuWL, LeeA, et al. The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: an open-label, randomized clinical trial. EBioMedicine. 2018;35:87-96.

[10] MagočT,Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011;27(21):2957-2963.

[11] EdgarRC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10(10):996-998.

[12] RavalAD,ThakkerD, NegiH,Vyas A,KaurH,SalkiniMW. Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2016;19(2):151-162.

[13] CaporasoJG,Kuczynski J,StombaughJ, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335-336.

[14] CaiJ,KimTS, JangJY, et al. In vitro and in vivo anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract. Lab Anim Res. 2014;30(2):28-34.

[15] WangYC,SuW, ZhangCY, et al. Protective effect of sea cucumber (Acaudina molpadioides) fucoidan against ethanol-induced gastric damage. Food Chem. 2012;133(4):1414-1419.

[16] JuffrieM,Rosalina I,DamayantiW,DjumhanaA,Ariani, AhmadH. The efficacy of fucoidan on gastric ulcer. Indonesian J Biotechnol. 2006;11(2):908-913.

[17] LiuM,MaL, ChenQC, et al. Fucoidan alleviates dyslipidemia and modulates gut microbiota in high-fat diet-induced mice. J Funct Foods. 2018;48:220-227.

[18] TangB,TangL, HuangC, et al. The effect of probiotics supplementation on gut microbiota after Helicobacter pylori eradication: a multicenter randomized controlled trial. Infect Dis Ther. 2021;10(1):317-333.

[19] ChenLY,XuWL, LeeA, et al. The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: an open-label, randomized clinical trial. EBioMedicine. 2018;35:87-96.

[20] LundbergJO,Carlström M,WeitzbergE. Metabolic effects of dietary nitrate in health and disease. Cell Metab. 2018;28(1):9-22.

[21] KapilV,Khambata RS,JonesDA, et al. The noncanonical pathway for in vivo nitric oxide generation: the nitrate-nitrite-nitric oxide pathway. Pharmacol Rev. 2020;72(3):692-766.

[22] BjörneHH,Petersson J,PhillipsonM,WeitzbergE,HolmL, LundbergJO. Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J Clin Invest. 2004;113(1):106-114.

[23] CompareD,RoccoA, Sanduzzi ZamparelliM,NardoneG. The gut bacteria-driven obesity development. Dig Dis. 2016;34(3):221-229.

[24] YapTWC,GanHM, LeeYP, et al. Helicobacter pylori eradication causes perturbation of the human gut microbiome in young adults. PLoS One. 2016;11(3):e151893.

[25] AdlerI,Denninghoff VC,AlvarezMI,AvagninaA,YoshidaR, ElsnerB. Helicobacter pylori associated with glossitis and halitosis. Helicobacter. 2005;10(4):312-317.

[26] FigliuoloVR,Dos Santos LM,AbaloA, et al. Sulfate-reducing bacteria stimulate gut immune responses and contribute to inflammation in experimental colitis. Life Sci. 2017;189:29-38.

[27] TsoiH,ChuESH, ZhangX, et al. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology. 2017;152(6):1419-1433.e5.

[28] ChenJZ,VitettaL. Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber. Clin Colorectal Cancer. 2018;17(3):e541-e544.

[29] SerinoM. SCFAs — the thin microbial metabolic line between good and bad. Nat Rev Endocrinol. 2019;15(6):318-319.

[30] MinL,LinM, ChenQC, et al. Fucoidan alleviates dyslipidemia and modulates gut microbiota in high-fat diet-induced mice. J Funct Foods. 2018;48:220-227.

RIGHTS & PERMISSIONS

2023 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.