Advertisement

Comparative effects of fresh and sterile fecal microbiota transplantation in an experimental animal model of necrotizing enterocolitis

  • Christian Prado
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Mariane Rocha Abatti
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Monique Michels
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Emily Córneo
    Correspondence
    Corresponding author at: UNESC – Universidade do Extremo Sul Catarinense, Av. Universitária, 1105 – Bairro Universitário, Criciúma - SC, CEP: 88806-000.
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Luana Cucker
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Heloisa Borges
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Rodrigo Dias
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Luana Bezerra Rocha
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Felipe Dal-Pizzol
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author
  • Cristiane Ritter
    Affiliations
    Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
    Search for articles by this author

      Abstract

      Introduction

      Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC.

      Methods

      One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations.

      Results

      Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect.

      Conclusion

      Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Pediatric Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • De Souza J.C.K.
        Cirurgia pediátrica – teoria e prática: enterocolite Necrosante.
        São Paulo: Editora Roca. 2008; : 385-397
        • Besner G.E.
        A pain in the NEC: research challenges and opportunities.
        J Pediatr Surg. 2015; 50: 23-29
        • Högberg N.
        • Stenbäck A.
        • Carlsson P.O.
        • et al.
        Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis.
        J Pediatr Surg. 2013; 48: 2308-2312
        • Bergholz R.
        • Zschiegner M.
        • Eschenburg G.
        • et al.
        Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis.
        J Pediatr Surg. 2013; 48: 2301-2307
        • Karadag A.
        • Ozdemir R.
        • Kurt A.
        • et al.
        Protective effects of dexpanthenol in an experimental model of necrotizing enterocolitis.
        J Pediatr Surg. 2015; 50: 1119-1124
        • Yu Y.
        • Klemann C.
        • Feng X.
        • et al.
        Increased inflammatory reaction to intestinal ischemia-reperfusion in neonatal versus adult mice.
        Eur J Pediatr Surg. 2015; 25: 46-50
        • Dominguez K.M.
        • Moss R.L.
        Necrotizing enterocolitis.
        Clin Perinatol. 2012; 39: 387-401
        • Roze E.
        • Ta B.
        • van der Ree M.
        • et al.
        Functional impairments at school age of children with necrotizing enterocolitis or spontaneous intestinal perforation.
        Pediatr Res. 2011; 70: 619-662
        • Rentea R.M.
        • Liedel J.L.
        • Fredrich K.
        • et al.
        Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model.
        J Pediatr Surg. 2013; 48: 124-128
        • Coran A.G.
        Pediatric surgery - seventh edition: necrotizing enterocolitis.
        Elsevier, Philadelphia2012: 1187-1207
        • Burke K.E.
        • Lamont J.T.
        Fecal transplantation for recurrent clostridium difficile infection in older adults: a review.
        J Am Geriatr Soc. 2013; 61: 1394-1398
        • Wang Y.
        • Hoenig J.D.
        • Malin K.J.
        • et al.
        16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis.
        ISME J. 2009; 3: 944-954
        • Claud E.C.
        Neonatal necrotizing enterocolitis -inflammation and intestinal immaturity.
        Antiinflamm Antiallergy Agents Med Chem. 2009; 8: 248-259
        • Berrington J.E.
        • Stewart C.J.
        • Cummings S.P.
        • et al.
        The neonatal bowel microbiome in health and infection.
        Curr Opin Infect Dis. 2014; 27: 236-243
        • Patole S.
        • Keil A.D.
        • Chang A.
        • et al.
        Effect of Bifidobacterium breve m-16v supplementation on fecal bifidobacteria in preterm neonates - a randomised double-blind placebo controlled trial.
        PLoS ONE. 2014; 9: e89511
        • Jenke A.C.
        • Postberg J.
        • Mariel B.
        • et al.
        S100A12 and hBD2 correlate with the composition of the fecal microflora in elbw infants and expansion of E. coli is associated with NEC.
        Biomed Res Int. 2013; 150372
        • Di Mauro A.
        • Neu J.
        • Riezzo G.
        • et al.
        Gastrointestinal function development and microbiota.
        Ital J Pediatr. 2013; 24 (39-15)
        • Berg D.
        • Clemente J.C.
        • Colombel J.F.
        Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?.
        Expert Rev Gastroenterol Hepatol. 2015; 9: 781-795
        • Jayasinghe T.N.
        • Chiavaroli V.
        • Holland D.J.
        • et al.
        The new era of treatment for obesity and metabolic disorders: evidence and expectations for gut microbiome transplantation.
        Front Cell Infect Microbiol. 2016; 19: 6-15
        • Konturek P.C.
        • Haziri D.
        • Brzozowski T.
        • et al.
        Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases.
        J Physiol Pharmacol. 2015; 66: 483-491
        • Esteve E.
        • Ricart W.
        • Fernández-Real J.M.
        Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve with insulin resistance?.
        Curr Opin Clin Nutr Metab Care. 2011; 14: 483-490
        • Li X.
        • Li X.
        • Shang Q.
        • et al.
        Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation.
        Free Radic Biol Med. 2017; 108: 32-43
        • Prado C.
        • Michels M.
        • Ávila P.
        • et al.
        The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.
        J Pediatr Surg. 2019; 54: 1578-1583
        • He Canxia
        • Shan Yujuan
        • Song Wei
        Targeting gut microbiota as a possible therapy for diabetes.
        Nutr Res. 2015; 35: 361-367
        • Berg D.
        • Clemente J.C.
        • Colombel J.F.
        Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?.
        Expert Rev Gastroenterol Hepatol. 2015; 9: 781-795
        • Zhou H.
        • Sun J.
        • Yu B.
        • et al.
        Gut microbiota absence and transplantation affect growth and intestinal functions: an investigation in a germ-free pig model.
        Anim Nutr. 2021; 7: 295-304
        • Barlow B.
        • Santulli T.V.
        • Heird W.C.
        • et al.
        An experimental study of acute neonatal enterocolitis - the importance of breast milk.
        J Pediatr Surg. 1974; 9: 587-595
        • Seekatz A.M.
        • Theriot C.M.
        • Molloy C.T.
        • et al.
        Fecal microbiota transplantation eliminates clostridium difficile in a murine model of relapsing disease.
        Infect Immun. 2015; 83: 3838-3846
        • Carlisle E.M.
        • Poroyko V.
        • Caplan M.S.
        • et al.
        Gram negative bacteria are associated with the early stages of necrotizing enterocolitis.
        PLoS ONE. 2011; 6: e18084
        • Zhu X.
        • Yang Y.
        • Gao W.
        • et al.
        Capparis spinosa alleviates DSS-induced ulcerative colitis via regulation of the gut microbiota and oxidative stress.
        Evid Based Complement Alternat Med. 2021; 151227876
        • Niu W.
        • Dong Y.
        • Fu Z.
        • et al.
        Effects of molecular weight of chitosan on anti-inflammatory activity and modulation of intestinal microflora in an ulcerative colitis model.
        Int J Biol Macromol. 2021; 15: 1927-1936
        • Liu H.
        • Wang H.H.
        Impact of microbiota transplant on resistome of gut microbiota in gnotobiotic piglets and human subjects.
        Front Microbiol. 2020; 19: 932
        • Stannard C.J.
        • Abiss J.S.
        • Wood J.M.
        Combined treatment with hydrogen peroxide and ultra-violet irradiation to reduce microbial contamination levels in pre-formed food packaging cartons.
        J Food Prot. 1983; 46: 1060-1064
        • Bayliss C.E.
        • Waites W.M.
        The combined effect of hydrogen peroxide and ultraviolet irradiation on bacterial spores.
        J Appl Bacteriol. 2020; 47: 236-269
        • Fung T.C.
        • Olson C.A.
        • Hsiao E.Y.
        Interactions between the microbiota, immune and nervous systems in health and disease.
        Nat Neurosci. 2017; 20: 145-155
        • Ávila P.R.M.
        • Michels M.
        • Vuolo F.
        • et al.
        Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora.
        Nutrition. 2020; 73: 1107-1127
        • Ganguli K.
        • Meng D.
        • Rautava S.
        • et al.
        Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation.
        Am J Physiol Gastrointest Liver Physiol. 2013; 304: 132-141
        • Good M.
        • Siggers R.H.
        • Sodhi C.P.
        • et al.
        Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium.
        Proc Natl Acad Sci USA. 2012; 109: 11330-11335
        • Yazji Ibrahim
        • Chhinder P.
        • Elizabeth S.K.
        • et al.
        Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling.
        Proc Natl Acad Sci USA. 2013; 110: 9451-9456
        • Barichello T.
        • Machado R.A.
        • Constantino L.
        • et al.
        Antioxidant treatment prevented late memory impairment in an animal model of sepsis.
        Crit Care Med. 2007; 35: 2186-2190
        • Liu J.
        • Miyake H.
        • Zhu H.
        • et al.
        Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis.
        J Pediatr Surg. 2020; 55: 1094-1098
        • Repa A.
        • Thanhaeuser M.
        • Endress D.
        • et al.
        Probiotics (Lactobacillus acidophilus and Bifidobacterium infantis) prevent NEC in VLBW infants fed breast milk but not formula [corrected].
        Pediatr Res. 2015; 77: 381-388
        • Mu C.
        • Yang Y.
        • Zhu W.
        Gut microbiota: the brain peacekeeper.
        Front Microbiol. 2016; 7: 345
        • Rea K.
        • Dinan T.G.
        • Cryan J.F.
        The microbiome: a key regulator of stress and neuroinflammation.
        Neurobiol Stress. 2016; 4: 23-33
        • Niño D.F.
        • et al.
        Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain.
        Sci Transl Med. 2018; : 10
        • Gurram B.
        • Sue P.K.
        Fecal microbiota transplantation in children: current concepts.
        Curr Opin Pediatr. 2019; 31: 623-629
        • Nowak A.
        • Hedenstierna M.
        • Ursing J.
        • et al.
        Efficacy of routine fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection: a retrospective cohort study.
        Int J Microbiol. 2019; 7 (395-127)
        • Kahn S.A.
        • Gorawara-Bhat R.
        • Rubin D.T
        Fecal bacteriotherapy for Ulcerative colitis: patients are ready, are we?.
        Inflamm Bowel Dis. 2012; 18: 676-684