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Influence of Blastocystis hominis on the small intestine and lactase enzyme activity

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Abstract

Blastocystis hominis is a cosmopolitan protozoan that has been associated with several gastrointestinal disturbances involving lactose intolerance. However, the underlying pathogenic factors remain indistinct. 20 Swiss albino mice were utilized and assembled into four groups, each of five mice: group-I: received neither infection nor lactose (healthy control), group-II: received a single dose of 10,000 cysts of Blastocystis and lactose diets in a dose of 12.5 g/day/mouse for 7 consecutive days starting from day 14 p.i., group-III: non-infected mice with oral doses of lactose (12.5 g/day/mouse) for 7 consecutive days (positive control), group-IV: infected mice on lactose free diet (negative control). We investigated the histopathological changes using H&E stain.s Also, lactase enzyme activity was measured using spectrophotometry and the production of TNF-α and apoptotic events were explored via immunohistochemistry and compared in the small intestine of all groups. The active inflammatory changes in the infected animals were moderate in the form of loss of villous architecture, increased ILC (P-value > 0.001) besides scattered forms of the parasite as compared to non-infected mice. There was a reduction in lactase enzyme activity p.i. The TNF-α levels were induced p.i. as compared to non-infected mice (P-value > 0.001). The expression of Bax protein was upgraded, while Bcl-2 expression decreased significantly with a reverse in Bax/Bcl2 ratio in infected animals. Blastocystis infection appears to humble lactase enzyme activity via the induction of apoptosis in the epithelial cells of the small intestinal brush border in a TNF-α associative pathway.

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References

  • Al-Fellani MA, Khan AH, Al-Gazoui RM, Zaid MK, Al-Ferjani MA (2007) Prevalence and clinical features of Blastocystis hominis infection among patients in Sebha. Libya. Sultan Qaboos Univ Med J 7(1):35–40

    PubMed  Google Scholar 

  • Al-Sadi R, Guo S, Ye D, Ma TY (2013) TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol 183(6):1871–1884

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ament ME, Rubin CE (1972) Relation of giardiasis to abnormal intestinal structure and function in gastrointestinal immunodeficiency syndrome. Gastroenterology 62:216–226

    CAS  PubMed  Google Scholar 

  • Ament ME, Ochs HD, David DD (1973) Structure and functions of the gastrointestinal tract in primary immunodeficiency syndrome. A study of 39 patients. Medicine 52:227–248

    CAS  PubMed  Google Scholar 

  • Arifin WN, Zahiruddin WM (2017) Sample size calculation in animal studies using resource equation approach. Malays J Med Sci MJMS 24(5):101

    PubMed  Google Scholar 

  • Bálint A, Dóczi I, Bereczki L, Gyulai R, Szűcs M, Farkas K, Urbán E, Nagy F, Szepes Z, Wittmann T (2014) Do not forget the stool examination!—cutaneous and gastrointestinal manifestations of Blastocystis sp. infection. Parasitol Res 113(4):1585–1590

    PubMed  Google Scholar 

  • Boorom KF, Smith H, Nimri L, Viscogliosi E, Spanakos G, Parkar U, Li LH, Zhou XN, Ok ÜZ, Leelayoova S, Jones MS (2008) Oh my aching gut: irritable bowel syndrome, Blastocystis, and asymptomatic infection. Parasites Vectors 1(1):1–16

    Google Scholar 

  • Buret AG, Chin AC, Scott KG (2003) Infection of human and bovine epithelial cells with Cryptosporidium andersoni induces apoptosis and disrupts tight junctional ZO-1: effects of epidermal growth factor. Int J Parasitol 33(12):1363–1371

    CAS  PubMed  Google Scholar 

  • Camilleri Á, Madsen K, Spiller R, Van Meerveld BG, Verne GN (2012) Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil 24(6):503–512

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dagci H, Ustun S, Taner MS, Ersoz G, Karacasu F, Budak S (2002) Protozoon infections and intestinal permeability. Acta Trop 81(1):1–5

    CAS  PubMed  Google Scholar 

  • Daniels LB, Coyle PJ, Chiao YB, Glew RH, Labow RS (1981) Purification and characterization of a cytosolic broad specificity beta-glucosidase from human liver. J Biol Chem 256(24):13004–13013

    CAS  PubMed  Google Scholar 

  • Day AJ, Canada FJ, Diaz JC, Kroon PA, Mclauchlan R, Faulds CB, Plumb GW, Morgan MR, Williamson G (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 468(2–3):166–170

    CAS  PubMed  Google Scholar 

  • Defaye M, Nourrisson C, Baudu E, Warwzyniak I, Bonnin V, Bonnet M, Poirier P (2018) Efficient and reproducible experimental infections of rats with Blastocystis spp. PLoS ONE 13(11):e0207669

    PubMed  PubMed Central  Google Scholar 

  • Drury RAB, Wallington EA (1980) Carleton’s histological technique, 5th edn. Churchill Livingstone, New York

    Google Scholar 

  • Erickson JA, Case K, Neider C, Johnson LM (2020) Stool reducing sugars and stool pH are poor screening tests for intestinal disaccharidase deficiencies in children. J Appl Lab Med 5(2):257–262

    PubMed  Google Scholar 

  • Gallagher PG, Venglarcik JS (1985) Blastocystis hominis enteritis. Pediatr Infect Dis J 4(5):556

    CAS  Google Scholar 

  • Graham DY, Sackman JW, Estes MK (1984) Pathogenesis of rotavirus-induced diarrhea. Dig Dis Sci 29(11):1028–1035

    CAS  PubMed  PubMed Central  Google Scholar 

  • Günther C, Neumann H, Neurath MF, Becker C (2013) Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut 62(7):1062–1071

    PubMed  Google Scholar 

  • Hooton D, Lentle R, Monro J, Wickham M, Simpson R (2015) The secretion and action of brush border enzymes in the mammalian small intestine. Rev Physiol Biochem Pharmacol 168:59–118

    CAS  PubMed  Google Scholar 

  • Iguchi A, Yoshikawa H, Yamada M, Kimata I, Arizono N (2009) Expression of interferon gamma and proinflammatory cytokines in the cecal mucosa of rats experimentally infected with Blastocystis sp. strain RN94–9. Parasitol Res 105(1):135

    PubMed  Google Scholar 

  • Jeddy TA, Farrington GH (1991) Blastocystis hominis complicating ulcerative colitis. J R Soc Med 84(10):623

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiménez-González D, Martínez-Flores W, Reyes-Gordillo J, Ramírez-Miranda M, Arroyo-Escalante S, Romero-Valdovinos M, Stark D, Souza-Saldivar V, Martínez- Hernández F, Flisser A, Olivo-Díaz A, Maravilla P (2012) Blastocystis infection is associated with irritable bowel syndrome in a Mexican patient population. Parasitol Res 110:1269–1275

    PubMed  Google Scholar 

  • Jimenez-Gonzalez DE, Martinez-Flores WA, Reyes-Gordillo J, Ramirez-Miranda ME, Arroyo-Escalante S, Romero-Valdovinos M et al (2012) Blastocystis infection is associated with irritable bowel syndrome in a Mexican patient population. Parasitol Res 110:1269–1275

    PubMed  Google Scholar 

  • Kaemmerer D, Peter L, Lupp A, Schulz S, Sänger J, Baum RP, Prasad V, Hommann M (2012) Comparing of IRS and Her2 as immunohistochemical scoring schemes in gastroenteropancreatic neuroendocrine tumors. Int J Clin Exp Pathol 5(3):187

    PubMed  PubMed Central  Google Scholar 

  • Kain KC, Noble MA, Freeman HJ, Barteluk RL (1987) Epidemiology and clinical features associated with Blastocystis hominis infection. Diagn Microbiol Infect Dis 8(4):235–244

    CAS  PubMed  Google Scholar 

  • Keshav S, Lawson L, Chung LP, Stein M, Perry VH, Gordon S (1990) Tumor necrosis factor mRNA localized to Paneth cells of normal murine intestinal epithelium by in situ hybridization. J Exp Med 171:327–332

    CAS  PubMed  Google Scholar 

  • Kök M, Çekin Y, Çekin AH, Uyar S, Harmandar F, Şahintürk Y (2019) The role of Blastocystis hominis in the activation of ulcerative colitis. Turk J Gastroenterol 30(1):40

    PubMed  Google Scholar 

  • Krajewski S, Krajewska M, Shabaik A, Wang HG, Irie S, Fong L, Reed JC (1994) Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Can Res 54(21):5501–5507

    CAS  Google Scholar 

  • Kumarasamy V, Kuppusamy UR, Samudi C, Kumar S (2013) Blastocystis sp. subtype 3 triggers higher proliferation of human colorectal cancer cells, HCT116. Parasitol Res 112(10):3551–3555

    PubMed  Google Scholar 

  • Kumarasamy V, Kuppusamy UR, Jayalakshmi P, Samudi C, Ragavan ND, Kumar S (2017) Exacerbation of colon carcinogenesis by Blastocystis sp. PLoS ONE 12(8):e0183097

    PubMed  PubMed Central  Google Scholar 

  • Kuprash DV, Udalova IA, Turetskaya RL, Kwiatkowski D, Rice NR, Nedospasov SA (1999) Similarities and differences between human and murine TNF promoters in their response to lipopolysaccharide. J Immunol 162(7):4045–4052

    CAS  PubMed  Google Scholar 

  • Lacroix S, Mancassola R, Naciri M, Laurent F (2001) Cryptosporidium parvum-specific mucosal immune response in C57BL/6 neonatal and gamma interferon-deficient mice: role of tumor necrosis factor alpha in protection. Infect Immun 69(3):1635–1642

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lake FR, Noble PW, Henson PM, Riches DW (1994) Functional switching of macrophage responses to tumor necrosis factor-alpha (TNF alpha) by interferons. Implications for the pleiotropic activities of TNF alpha. J Clin Invest 93(4):1661–1669

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Fang R, Wei Z, Wu J, Li X, Li W (2020) Giardia duodenalis Induces apoptosis in intestinal epithelial cells via reactive oxygen species-mediated mitochondrial pathway in vitro. Pathogens 9(9):693

    CAS  PubMed Central  Google Scholar 

  • Mirza H, Wu Z, Teo JD, Tan KS (2012) Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases. Cell Microbiol 14:1474–1484

    CAS  PubMed  Google Scholar 

  • Moe KT, Singh M, Howe J, Ho LC, Tan SW, Chen XQ, Yap EH (1997) Experimental Blastocystis hominis infection in laboratory mice. Parasitol Res 83(4):319–321

    CAS  PubMed  Google Scholar 

  • Muñoz-Carrillo JL, Muñoz-Escobedo JJ, Maldonado-Tapia CH, Chávez-Ruvalcaba F, Moreno-García MA (2017) Resiniferatoxin lowers TNF-α, NO and PGE2 in the intestinal phase and the parasite burden in the muscular phase of Trichinella spiralis infection. Parasite Immunol 39(1):e12393

    Google Scholar 

  • Nair AB, Jacob S (2016) A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 7(2):27

    PubMed  PubMed Central  Google Scholar 

  • O’Gorman MA, Orenstein SR, Proujansky R, Wadowsky RM, Putnam PE, Kocoshis SA (1993) Prevalence and characteristics of Blastocystis horninis infection in children. Clin Pediatr 32(2):91–96

    CAS  Google Scholar 

  • Parker A, Vaux L, Patterson AM, Modasia A, Muraro D, Fletcher AG, Byrne HM, Maini PK, Watson AJ, Pin C (2019) Elevated apoptosis impairs epithelial cell turnover and shortens villi in TNF-driven intestinal inflammation. Cell Death Dis 10(2):1–13

    Google Scholar 

  • Pavanelli MF, Kaneshima EN, Uda CF, Colli CM, Falavigna-Guilherm AL, Gomes ML (2015) Pathogenicity of Blastocystis sp. to the gastrointestinal tract of mice: relationship between inoculum size and period of infection. Rev Inst Med Trop Sao Paulo 57(6):467–472

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poirier P, Wawrzyniak I, Vivarès CP, Delbac F, El Alaoui H (2012) New insights into Blastocystis spp.: a potential link with irritable bowel syndrome. PLoS Pathog 8(3):e1002545

    CAS  PubMed  PubMed Central  Google Scholar 

  • Puthia MK, Sio SW, Lu J, Tan KS (2006) Blastocystis ratti induces contact-independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells. Infect Immun 74:4114–4123

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rings EH, Grand RJ, Büller HA (1994) Lactose intolerance and lactase deficiency in children. Curr Opin Pediatr 6(5):562–567

    CAS  PubMed  Google Scholar 

  • Rossignol JF, Kabil SM, Said M, Samir H, Younis AM (2005) Effect of nitazoxanide in persistent diarrhea and enteritis associated with Blastocystis hominis. Clin Gastroenterol Hepatol 3(10):987–991

    CAS  PubMed  Google Scholar 

  • Saghaug CS, Sørnes S, Peirasmaki D, Svärd S, Langeland N, Hanevik K (2015) Human memory CD4+ T cell immune responses against Giardia lamblia. Clin Vaccine Immunol 23(1):11–18

    PubMed  Google Scholar 

  • Sarhan R, Saad G, Ezz Eldin H, Hetta M (2019) A novel impact of Boswellia serrata on Blastocystis spp. infected mice. Parasitol United J 12(2):116–122

    Google Scholar 

  • Scanlan P (2012) Blastocystis: past pitfalls and future perspectives. Trends Parasitol 28:327–334

    PubMed  Google Scholar 

  • Silvia WJ, Hatler TB, Nugent AM, Da Fonseca LL (2002) Ovarian follicular cysts in dairy cows: an abnormality in folliculogenesis. Domest Anim Endocrinol 23(1–2):167–177

    CAS  PubMed  Google Scholar 

  • Singh KD, Bhasin DK, Rana SV, Vaiphei K, Katyal R, Vinayak VK, Singh K (2000) Effect of Giardia lamblia on duodenal disaccharidase levels in humans. Trop Gastroenterol off J Digest Dis Found 21(4):174–176

    CAS  Google Scholar 

  • Steck N, Mueller K, Schemann M, Haller D (2011) Bacterial proteases in IBD and IBS. Gut. https://doi.org/10.1136/gutjnl-2011-300775

    Article  PubMed  Google Scholar 

  • Sundararajan R, Cuconati A, Nelson D, White E (2001) Tumor necrosis factor-α induces Bax-Bak interaction and apoptosis, which is inhibited by adenovirus E1B 19K. J Biol Chem 276(48):45120–45127

    CAS  PubMed  Google Scholar 

  • Tan XIAODI, Hsueh W, Gonzalez-Crussi F (1993) Cellular localization of tumor necrosis factor (TNF)-alpha transcripts in normal bowel and in necrotizing enterocolitis. TNF gene expression by Paneth cells, intestinal eosinophils, and macrophages. Am J Pathol 142(6):1858

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tan K, Mirza H, Teo J, Wu B, Macary P (2010) Current views on the clinical relevance of Blastocystis spp. Curr Infect Dis Rep 12:28–35

    PubMed  Google Scholar 

  • Tsang TK, Levin BS, Morse SR (1989) Terminal ileitis associated with Blastocystis hominis infection. Am J Gastroenterol 84(7):798–799

    CAS  PubMed  Google Scholar 

  • Tungtrongchitr A, Manatsathit S, Kositchaiwat C, Ongrotchanakun J, Munkong N, Chinabutr P, Leelakusolvong S, Chaicumpa W (2004) (2004): Blastocystis hominis infection in irritable bowel syndrome patients. Southeast Asian J Trop Med Public Health 4(35):705–710

    Google Scholar 

  • Wang L (2004) Changing patterns in intestinal parasitic infections among Southeast Asian laborers in Taiwan. Parasitol Res 92:18–21

    PubMed  Google Scholar 

  • Wang W, Owen H, Traub RJ, Cuttell L, Inpankaew T, Bielefeldt-Ohmann H (2014) Molecular epidemiology of Blastocystis in pigs and their in-contact humans in Southeast Queensland, Australia, and Cambodia. Vet Parasitol 203(3–4):264–269

    PubMed  Google Scholar 

  • Wawrzyniak I, Poirier P, Viscogliosi E, Dionigia M, Texier C, Delbac F, El Alaoui H (2013) Blastocystis, an unrecognized parasite: an overview of pathogenesis and diagnosis. Ther Adv Infect Dis 1(5):167–178

    PubMed  PubMed Central  Google Scholar 

  • Westphal D, Kluck RM, Dewson G (2014) Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ 21(2):196–205

    CAS  PubMed  Google Scholar 

  • Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, Goodwin RG (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3(6):673–682

    CAS  PubMed  Google Scholar 

  • Yakoob J, Jafri W, Beg MA, Abbas Z, Naz S, Islam M et al (2010) Irritable bowel syndrome: is it associated with genotypes of Blastocystis hominis. Parasitol Res 106:1033–1038

    PubMed  Google Scholar 

  • Yakoob J, Abbas Z, Khan R, Hamid S, Awan S, Jafri W (2011) Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan. Saudi J Gastroenterol off J Saudi Gastroenterol Assoc 17(6):371–375. https://doi.org/10.4103/1319-3767.87176

    Article  Google Scholar 

  • Yakoob J, Abbas Z, Usman MW, Sultana A, Islam M, Awan S, Ahmad Z, Hamid S, Jafri W (2014) Cytokine changes in colonic mucosa associated with Blastocystis spp. subtypes 1 and 3 in diarrhoea-predominant irritable bowel syndrome. Parasitology 141(7):957

    CAS  PubMed  Google Scholar 

  • Yao FR, Qiao JY, Zhao Y et al (2005) Experimental infection of mice with Blastocystis hominis. Chin J Parasitol Parasitic Dis 23(6):444–448

    Google Scholar 

  • Yu YR, Deng MJ, Lu WW, Zhang JS, Jia MZ, Huang J, Qi YF (2014) Endoplasmic reticulum stress-mediated apoptosis is activated in intestines of mice with Trichinella spiralis infection. Exp Parasitol 145:1–6

    CAS  PubMed  Google Scholar 

  • Zuckerman MJ, Watts MT, Ho HOI, Meriano FV (1994) Blastocystis hominis infection and intestinal injury. Am J Med Sci 308(2):96–101

    CAS  PubMed  Google Scholar 

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Correspondence to Enas A. El Saftawy.

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All procedures were performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines and were approved by the institution accountable for animal ethics regarding care for animals and safe discarding of their waste products at TBRI and were approved by ethical committee of Kasr Al-Ainy school of Medicine, TBRI and the Cairo University of Institutional Animal Care and Use Committee (CU-IACUC) and was logged by CU/III/F/6/20.

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Basuony, G.A., M.A.Basyoni, M., Negm, M.S.I. et al. Influence of Blastocystis hominis on the small intestine and lactase enzyme activity. J Parasit Dis 46, 243–253 (2022). https://doi.org/10.1007/s12639-021-01442-6

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