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Chinese liver fluke Clonorchis sinensis infection changes the gut microbiome and increases probiotic Lactobacillus in mice

  • Helminthology - Short Communication
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Abstract

Chinese liver fluke Clonorchis sinensis changes the host’s immune system. Recently, it has been reported that helminths including C. sinensis can ameliorate immune-related diseases such as allergy. In addition, recent studies showed that helminth infection can alleviate immune-mediated disorders by altering the gut microbiome. However, changes in the gut microbiome due to C. sinensis have not been reported yet. In this study, changes in the gut microbiome of C57BL/6 mice infected with C. sinensis metacercariae were evaluated over time. Stool was analyzed by 16S rRNA amplicon analysis using high-throughput sequencing technology. There was no apparent difference in species richness and diversity between the infected and control groups. However, the composition of the microbiome was different between the infected and control groups at 20 days and 30 days post-infection, and the difference disappeared at 50 days post-infection. In particular, this microbiome alteration was associated with a change in the relative abundance of genus Lactobacillus and the probiotic Lactobacillus species that are known to have an immune-modulation role in immune-mediated diseases.

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References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  • Anderson MJ (2001) A new method for non-parametric multivariate analysis of variance. Austral Eco 26:32–46

    Google Scholar 

  • Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broadhurst MJ, Ardeshir A, Kanwar B, Mirpuri J, Gundra UM, Leung JM, Wiens KE, Vujkovic-Cvijin I, Kim CC, Yarovinsky F, Lerche NW, McCune JM, Loke P (2012) Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon. PLoS Pathog 8:e1003000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi MH, Chang YS, Lim MK, Bae YM, Hong ST, Oh JK, Yun EH, Bae MJ, Kwon HS, Lee SM, Park HW, Min KU, Kim YY, Cho SH (2011) Clonorchis sinensis infection is positively associated with atopy in endemic area. Clin Exp Allergy 41:697–705

    Article  PubMed  Google Scholar 

  • Choi YK, Yoon BI, Won YS, Lee CH, Hyun BH, Kim HC, Oh GT, Kim DY (2003) Cytokine responses in mice infected with Clonorchis sinensis. Parasitol Res 91:87–93

    Article  PubMed  Google Scholar 

  • Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE, Nutman TB (2003) Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol 111:995–1000

    Article  PubMed  Google Scholar 

  • Deenonpoe R, Chomvarin C, Pairojkul C, Chamgramol Y, Loukas A, Brindley PJ, Sripa B (2015) The carcinogenic liver fluke Opisthorchis viverrini is a reservoir for species of Helicobacter. Asian Pac J Cancer Prev 16:1751–1758

    Article  PubMed  Google Scholar 

  • Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26:2460–2461

    Article  CAS  PubMed  Google Scholar 

  • Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R (2011) UCHIME improves sensitivity and speed of chimera detection. Bioinformatics 27:2194–2200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feary J, Britton J, Leonardi-Bee J (2011) Atopy and current intestinal parasite infection: a systematic review and meta-analysis. Allergy 66:569–578

    Article  CAS  PubMed  Google Scholar 

  • Finlay CM, Stefanska AM, Coleman MM, Jahns H, Cassidy JP, McLoughlin RM, Mills KHG (2017) Secreted products of Fasciola hepatica inhibit the induction of T cell responses that mediate allergy. Parasite Immunol 39:Epub

  • Fu L, Niu B, Zhu Z, Wu S, Li W (2012) CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 28:3150–3152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gower JC (1966) Some distance properties of latent root and vector methods used in multivariate analysis. Biometrika 53:325–338

    Article  Google Scholar 

  • Hong ST (2003) Clonorchis sinensis. In: Miliotis MD, Bier JW (ed) International handbook of foodborne pathogens. Marcel Dekker, New York, Ch. 35

  • Itthitaetrakool U, Pinlaor P, Pinlaor S, Chomvarin C, Dangtakot R, Chaidee A, Wilailuckana C, Sangka A, Lulitanond A, Yongvanit P (2016) Chronic Opisthorchis viverrini infection changes the liver microbiome and promotes Helicobacter growth. PLoS One 11:e0165798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong YI, Kim SH, Ju JW, Cho SH, Lee WJ, Park JW, Park YM, Lee SE (2011) Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions. Biochem Biophys Res Commun 407:793–800

    Article  CAS  PubMed  Google Scholar 

  • Kaewpitoon SJ, Loyd RA, Rujirakul R, Panpimanmas S, Matrakool L, Tongtawee T, Kootanavanichpong N, Pengsaa P, Kompor P, Chavengkun W, Kujapun J, Norkaew J, Ponphimai S, Padchasuwan N, Polsripradist P, Eksanti T, Phatisena T, Kaewpitoon N (2016) Helicobacter species are possible risk factors of cholangiocarcinoma. Asian Pac J Cancer Prev 17:37–44

    Article  PubMed  Google Scholar 

  • Karimi K, Inman MD, Bienenstock J, Forsythe P (2009) Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med 179:186–193

    Article  CAS  PubMed  Google Scholar 

  • Kim EM, Kwak YS, Yi MH, Kim JY, Sohn WM, Yong TS (2017) Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo. PLoS Negl Trop Dis 11:e0005614

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim JY, Yi MH, Hwang Y, Lee JY, Lee IY, Yong D, Yong TS (2018a) 16S rRNA profiling of the Dermatophagoides farinae core microbiome: Enterococcus and Bartonella. Clin Exp Allergy 48:607–610

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, Kim EM, Yi MH, Lee J, Lee S, Hwang Y, Yong D, Sohn WM, Yong TS (2018b) Intestinal fluke Metagonimus yokogawai infection increases probiotic Lactobacillus in mouse cecum. Exp Parasitol 193:45–50

    Article  PubMed  Google Scholar 

  • Li RW, Wu S, Li W, Navarro K, Couch RD, Hill D, Urban JF Jr (2012) Alterations in the porcine colon microbiota induced by the gastrointestinal nematode Trichuris suis. Infect Immun 80:2150–2157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Fatheree NY, Mangalat N, Rhoads JM (2012) Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestine. Am J Physiol Gastrointest Liver Physiol 302:608–617

    Article  CAS  Google Scholar 

  • Liu Y, Fatheree NY, Dingle BM, Tran DQ, Rhoads JM (2013) Lactobacillus reuteri DSM 17938 changes the frequency of Foxp3+ regulatory T cells in the intestine and mesenteric lymph node in experimental necrotizing enterocolitis. PLoS One 8:e56547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lozupone C, Knight R (2005) UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 71:8228–8235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maizels RM, Yazdanbakhsh M (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 3:733–744

    Article  CAS  PubMed  Google Scholar 

  • Masella AP, Bartram AK, Truszkowski JM, Brown DG, Neufeld JD (2012) PANDAseq: paired-end assembler for illumina sequences. BMC bioinformatics 13:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Myers EW, Miller W (1988) Optimal alignments in linear space. Comput Appl Biosci 4:11–17

    CAS  PubMed  Google Scholar 

  • Osborne LC, Monticelli LA, Nice TJ, Sutherland TE, Siracusa MC, Hepworth MR, Tomov VT, Kobuley D, Tran SV, Bittinger K, Bailey AG, Laughlin AL, Boucher JL, Wherry EJ, Bushman FD, Allen JE, Virgin HW, Artis D (2014) Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science 345:578–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plieskatt JL, Deenonpoe R, Mulvenna JP, Krause L, Sripa B, Bethony JM, Brindley PJ (2013) Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome. FASEB J 27:4572–4584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rausch S, Held J, Fischer A, Heimesaat MM, Ku¨hl, AA, Bereswill S, Hartmann S (2013) Small intestinal nematode infection of mice is associated with increased enterobacterial loads alongside the intestinal tract. PLoS ONE 8:e74026

  • Rim HJ (2005) Clonorchiasis: an update. J Helminthol 79:269–281

    Article  PubMed  Google Scholar 

  • Saltykova IV, Petrov VA, Logacheva MD, Ivanova PG, Merzlikin NV, Sazonov AE, Ogorodova LM, Brindley PJ (2016) Biliary microbiota, gallstone disease and infection with Opisthorchis felineus. PLoS Negl Trop Dis 10:e0004809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open-source, platform-independent, community supported software for describing and comparing microbial communities. Appl Environ Microbiol 75:7537–7541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12:R60

    Article  PubMed  PubMed Central  Google Scholar 

  • Shannon C, Petigara N, Seshasai S (1948) A mathematical theory of communication. Bell Syst Tech J 27:379–423

    Article  Google Scholar 

  • Uddin MH, Li S, Bae YM, Choi MH, Hong ST (2012) Strain variation in the susceptibility and immune response to Clonorchis sinensis infection in mice. Parasitol Int 61:118–123

    Article  CAS  PubMed  Google Scholar 

  • Walk ST, Blum AM, Ewing SA, Weinstock JV, Young VB (2010) Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflamm Bowel Dis 16:1841–1849

    Article  PubMed  Google Scholar 

  • Wammes LJ, Mpairwe H, Elliott AM, Yazdanbakhsh M (2014) Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect Dis 14:1150–1162

    Article  CAS  PubMed  Google Scholar 

  • Yoon SH, Ha SM, Kwon S, Lim J, Kim Y, Seo H, Chun J (2017) Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int J Syst Evol Microbiol 67:1613–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaiss MM, Rapin A, Lebon L, Dubey LK, Mosconi I, Sarter K, Piersigilli A, Menin L, Walker AW, Rougemont J, Paerewijck O, Geldhof P, McCoy KD, Macpherson AJ, Croese J, Giacomin PR, Loukas A, Junt T, Marsland BJ, Harris NL (2015) The intestinal microbiota contributes to the ability of helminths to modulate allergic inflammation. Immunity 43:998–1010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaiss MM, Harris NL (2016) Interactions between the intestinal microbiome and helminth parasites. Parasite Immunol 38:5–11

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MEST; numbers NRF-2016R1A2B4016194 and 2011-0012166).

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Correspondence to Tai-Soon Yong.

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The authors declare that they have no conflict of interest.

Research involving animals

All animal protocols were approved by the Institutional Animal Care and Use Committee at Yonsei University College of Medicine (No. 2015–0339). Animal experiments were carried out in animal biosafety level-3 (ABL-3) facilities in accordance with standard management practices.

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Section Editor: Ramaswamy Kalyanasundaram

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Fig. S1

Box plots of relative abundance of Lactobacillus over time. * p < 0.05 in Wilcoxon rank-sum test. (PDF 33.7 kb)

Fig. S2

Eggs of Clonorchis sinensis in liver section of infected mouse at 50 days post-infection (hematoxylin and eosin staining, 400x). Black arrows indicate the eggs. (PDF 209 kb)

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Kim, J.Y., Kim, EM., Yi, Mh. et al. Chinese liver fluke Clonorchis sinensis infection changes the gut microbiome and increases probiotic Lactobacillus in mice. Parasitol Res 118, 693–699 (2019). https://doi.org/10.1007/s00436-018-6179-x

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