Effects of the Exclusive Enteral Nutrition on the Microbiota Profile of Patients with Crohn's Disease: A Systematic Review

Simona Gatti, Tiziana Galeazzi, Elisa Franceschini, Roberta Annibali, Veronica Albano, Anil Kumar Verma, Maria De Angelis, Maria Elena Lionetti, Carlo Catassi, Simona Gatti, Tiziana Galeazzi, Elisa Franceschini, Roberta Annibali, Veronica Albano, Anil Kumar Verma, Maria De Angelis, Maria Elena Lionetti, Carlo Catassi

Abstract

The mechanisms behind the efficacy of exclusive enteral nutrition (EEN) in Crohn's disease (CD) remain poorly understood, despite the high rate of treatment response. Evidence accumulated in the last 20 years suggests that a positive shift of the disrupted microbiota is one of the treatment effects. The purpose of this study was to critically review and summarize data reporting the microbiological effects of EEN in patients with CD. Fourteen studies were considered in the review, overall involving 216 CD patients on EEN. The studies were heterogeneous in methods of microbiota analysis and exclusion criteria. The most frequently reported effect of EEN was a reduction in microbiota diversity, reversible when patients returned to a normal diet. The effect of EEN on specific bacteria was very variable in the different studies, partially due to methodological limitations of the mentioned studies. The EEN seem to induce some metabolomic changes, which are different in long-term responder patients compared to patients that relapse earlier. Bacterial changes can be relevant to explaining the efficacy of EEN; however, microbiological data obtained from rigorously performed studies and derived from last generation techniques are largely inconsistent.

Keywords: 16S rRNA; Crohn’s disease; Faecalibacterium prausntzii; IBD; exclusive enteral nutrition; metabolome; microbiota; next generation sequencing.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Orel R., Kamhi Trop T. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease. World J. Gastroenterol. 2014;20:11505–11524. doi: 10.3748/wjg.v20.i33.11505.
    1. Serban D.E. The gut microbiota in the metagenomics era: Sometimes a friend, sometimes a foe. Roum. Arch. Microbiol. Immunol. 2011;70:134–140.
    1. Hold G.L., Smith M., Grange C., Watt E.R., El-Omar E.M., Mukhopadhya I. Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years? World J. Gastroenterol. 2014;20:1192–1210. doi: 10.3748/wjg.v20.i5.1192.
    1. De Cruz P., Prideaux L., Wagner J., Ng S.C., McSweeney C., Kirkwood C., Morrison M., Kamm M.A. Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. Inflamm. Bowel Dis. 2012;18:372–390. doi: 10.1002/ibd.21751.
    1. Serban D.E. Microbiota in Inflammatory Bowel disease pathogenesis and therapy: Is it all about diet? Nutr. Clin. Pract. 2015;30:760–779. doi: 10.1177/0884533615606898.
    1. Gevers D., Kugathasan S., Denson L.A., Vázquez-Baeza Y., Van Treuren W., Ren B., Schwager E., Knights D., Song S.J., Yassour M., et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014;15:382–392. doi: 10.1016/j.chom.2014.02.005.
    1. Lee D., Albenberg L., Compher C., Baldassano R., Piccoli D., Lewis J.D., Wu G.D. Diet in the pathogenesis and treatment of inflammatory bowel diseases. Gastroenterology. 2015;148:1087–1106. doi: 10.1053/j.gastro.2015.01.007.
    1. Penagini F., Dilillo D., Borsani B., Cococcioni L., Galli E., Bedogni G., Zuin G., Zuccotti G.V. Nutrition in Pediatric Inflammatory Bowel Disease: From Etiology to Treatment. A Systematic Review. Nutrients. 2016 doi: 10.3390/nu8060334.
    1. Ruemmele F.M., Veres G., Kolho K.L., Griffiths A., Levine A., Escher J.C., Amil Dias J., Barabino A., Braegger C.P., Bronsky J., et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J. Crohns Colitis. 2014;8:1179–1207. doi: 10.1016/j.crohns.2014.04.005.
    1. Grover Z., Muir R., Lewindon P. Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn’s disease. J. Gastroenterol. 2014;49:638–645. doi: 10.1007/s00535-013-0815-0.
    1. Borrelli O., Cordischi L., Cirulli M., Paganelli M., Labalestra V., Uccini S., Russo P.M., Cucchiara S. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease: A randomized controlled open-label trial. Clin. Gastroenterol. Hepatol. 2006;4:744–753. doi: 10.1016/j.cgh.2006.03.010.
    1. Berni Canani R., Terrin G., Borrelli O., Romano M.T., Manguso F., Coruzzo A., D’Armiento F., Romeo E.F., Cucchiara S. Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn’s disease. Dig. Liver Dis. 2006;38:381–387. doi: 10.1016/j.dld.2005.10.005.
    1. Ludvigsson J.F., Krantz M., Bodin L., Stenhammar L., Lindquist B. Elemental versus polymeric enteral nutrition in paediatric Crohn’s disease: A multicentre randomized controlled trial. Acta Paediatr. 2004;93:327–335. doi: 10.1111/j.1651-2227.2004.tb02956.x.
    1. Verma S., Brown S., Kirkwood B., Giaffer M.H. Polymeric versus elemental diet as primary treatment in active Crohn’s disease: A randomized, double-blind trial. Am. J. Gastroenterol. 2000;95:735–739. doi: 10.1111/j.1572-0241.2000.01527.x.
    1. Rubio A., Pigneur B., Garnier-Lengline H., Talbotec C., Schmitz J., Canioni D., Goulet O., Ruemmele F.M. The efficacy of exclusive nutritional therapy in paediatric Crohn’s disease, comparing fractionated oral vs. continuous enteral feeding. Aliment. Pharmacol. Ther. 2011;33:1332–1339. doi: 10.1111/j.1365-2036.2011.04662.x.
    1. Ruemmele F.M., Pigneur B., Garnier-Lengliné H. Enteral nutrition as treatment option for Crohn’s disease: In kids only? Nestlé Nutr. Inst. Workshop Ser. 2014;79:115–123. doi: 10.1159/0003607.
    1. Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214.
    1. Lozupone C.A., Stombaugh J.I., Gordon J.I., Jansson J.K., Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–230. doi: 10.1038/nature11550.
    1. Shah R., Kellermayer R. Associations of therapeutic enteral nutrition. Nutrients. 2014;21:5298–5311. doi: 10.3390/nu6115298.
    1. Lagier J.C., Hugon P., Khelaifia S., Fournier P.E., La Scola B., Raoult D. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin. Microbiol. Rev. 2015;28:237–264. doi: 10.1128/CMR.00014-14.
    1. Schmidt T.S.B., Matias Rodrigues J.F., von Mering C. Ecological consistency of SSU rRNA-based operational taxonomic units at a global scale. PLoS Comput. Biol. 2014;10 doi: 10.1371/journal.pcbi.1003594.
    1. Sharpton T.J. An introduction to the analysis of shotgun metagenomic data. Front. Plant. Sci. 2014 doi: 10.3389/fpls.2014.00209.
    1. Lionetti P., Callegari M.L., Ferrari S., Cavicchi M.C., Pozzi E., de Martino M., Morelli L. Enteral nutrition and microflora in pediatric Crohn’s disease. J. Parenter. Enter. Nutr. 2005;29:S173–S175. doi: 10.1177/01486071050290S4S173.
    1. Leach S.T., Mitchell H.M., Eng W.R., Zhang L., Day A.S. Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn’s disease. Aliment. Pharmacol. Ther. 2008;28:724–733. doi: 10.1111/j.1365-2036.2008.03796.x.
    1. Jia W., Whitehead R.N., Griffiths L., Dawson C., Waring R.H., Ramsden D.B., Hunter J.O., Cole J.A. Is the abundance of Faecalibacterium prausnitzii relevant to Crohn’s disease? FEMS Microbiol. Lett. 2010;310:138–144. doi: 10.1111/j.1574-6968.2010.02057.x.
    1. Shiga H., Kajiura T., Shinozaki J., Takagi S., Kinouchi Y., Takahashi S., Negoro K., Endo K., Kakuta Y., Suzuki M., et al. Changes of faecal microbiota in patients with Crohn’s disease treated with an elemental diet and total parenteral nutrition. Dig. Liver. Dis. 2012;44:736–742. doi: 10.1016/j.dld.2012.04.014.
    1. Tjellstrom B., Hogberg L., Stenhammar L., Magnusson K.E., Midtvedt T., Norin E., Sundqvist T. Effect of exclusive enteral nutrition on gut microflora function in children with Crohn’s disease. Scand. J. Gastroenterol. 2012;47:1454–1459. doi: 10.3109/00365521.2012.703234.
    1. D’Argenio V., Precone V., Casaburi G., Miele E., Martinelli M., Staiano A., Salvatore F., Sacchetti L. An altered gut microbiome profile in a child affected by Crohn’s disease normalized after nutritional therapy. Am. J. Gastroenterol. 2013;108:851–852. doi: 10.1038/ajg.2013.46.
    1. Gerasimidis K., Bertz M., Hanske L., Junick J., Biskou O., Aguilera M., Garrick V., Russell R.K., Blaut M., McGrogan P., et al. Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn’s disease during enteral nutrition. Inflamm. Bowel. Dis. 2014;20:861–871. doi: 10.1097/MIB.0000000000000023.
    1. Quince C., Zeeshan Ijaz U., Loman N., Eren A.M., Saulnier D., Russell J., Haig S.J., Calus S.T., Quick J., Barclay A., et al. Extensive modulation of the fecal metagenome in children with Crohn’s disease during Exclusive Enteral Nutrition. Am. J. Gastroenterol. 2015;110:1718–1729. doi: 10.1038/ajg.2015.357.
    1. Lewis J.D., Chen E.Z., Baldassano R.N., Otley A.R., Griffiths A.M., Lee D., Bittinger K., Bailey A., Friedman E.S., Hoffmann C., et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe. 2015;18:489–500. doi: 10.1016/j.chom.2015.09.008.
    1. Kaakoush N.O., Day A.S., Leach S.T., Lemberg D.A., Nielsen S., Mitchell H.M. Effect of exclusive enteral nutrition on the microbiota of children with newly diagnosed Crohn’s disease. Clin. Transl. Gastroenterol. 2015;6:1–11. doi: 10.1038/ctg.2014.21.
    1. Schwerd T., Frivolt K., Clavel T., Lagkouvardos I., Katona G., Mayr D., Uhlig H.H., Haller D., Koletzko S., Bufler P. Exclusive enteral nutrition in active pediatric Crohn disease: Effects on intestinal microbiota and immune regulation. J. Allergy Clin. Immunol. 2016;138:592–596. doi: 10.1016/j.jaci.2015.12.1331.
    1. Guinet-Charpentier C., Lepage P., Morali A., Chamaillard M., Peyrin-Biroulet L. Effects of enteral polymeric diet on gut microbiota in children with Crohn’s disease. Gut. 2017;66:194–195. doi: 10.1136/gutjnl-2015-311058.
    1. Dunn K.A., Moore-Connors J., MacIntyre B., Stadnyk A., Thomas N.A., Noble A., Mahdi G., Rashid M., Otley A.R., Bielawski J.P., et al. The gut microbiome of pediatric Crohn’s disease patients differs from healthy controls in genes that can influence the balance between a healthy and dysregulated immune response. Inflamm. Bowel Dis. 2016;22:2607–2618. doi: 10.1097/MIB.0000000000000949.
    1. Dunn K.A., Moore-Connors J., MacIntyre B., Stadnyk A.W., Thomas N.A., Noble A., Mahdi G., Rashid M., Otley A.R., Bielawski J.P., et al. Early changes in microbial community structure are associated with sustained remission after nutritional treatment of pediatric Crohn’s disease. Inflamm. Bowel Dis. 2016;22:2853–2862. doi: 10.1097/MIB.0000000000000956.
    1. Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermúdez-Humarán L.G., Gratadoux J.J., Blugeon S., Bridonneau C., Furet J.P., Corthier G., et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl. Acad. Sci. USA. 2008;105:16731–16736. doi: 10.1073/pnas.0804812105.
    1. Sokol H., Seksik P., Furet J.P., Firmesse O., Nion-Larmurier I., Beaugerie L., Cosnes J., Corthier G., Marteau P., Doré J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm. Bowel Dis. 2009;15:1183–1189. doi: 10.1002/ibd.20903.
    1. McNeil N.I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 1984;39:338–342.
    1. Vinolo M.A.R., Rodrigues H.G., Nachbar R.T., Curi R. Regulation of Inflammation by Short Chain Fatty Acids. Nutrients. 2011;3:858–876. doi: 10.3390/nu3100858.
    1. Elson C.O., Sartor R.B., Tennyson G.S., Riddell R.H. Experimental models of Inflammatory bowel disease. Gastroenterology. 1995;109:1344–1367. doi: 10.1016/0016-5085(95)90599-5.
    1. Fabia R., Willén R., Ar’Rajab A., Andersson R., Ahrén B., Bengmark S. Acetic acid-induced colitis in the rat: A reproducible experimental model for acute ulcerative colitis. Eur. Surg. Res. 1992;24:211–225. doi: 10.1159/000129209.
    1. Slezak K., Hanske L., Loh G., Blaut M. Increased bacterial putrescine has no impact on gut morphology and physiology in gnotobiotic adolescent mice. Benef. Microbes. 2013;4:253–266. doi: 10.3920/BM2012.0047.
    1. Stearns J.C., Lynch M.D., Senadheera D.B., Tenenbaum H.C., Goldberg M.B., Cvitkovitch D.G., Croitoru K., Moreno-Hagelsieb G., Neufeld J.D. Bacterial biogeography of the human digestive tract. Sci. Rep. 2011 doi: 10.1038/srep00170.
    1. Lavelle A., Lennon G., O’Sullivan O., Docherty N., Balfe A., Maguire A., Mulcahy H.E., Doherty G., O’Donoghue D., Hyland J., et al. Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers. Gut. 2015;64:1553–1561. doi: 10.1136/gutjnl-2014-307873.
    1. Dethlefsen L., Relman D.A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl. Acad. Sci. USA. 2011;108:4554–4561. doi: 10.1073/pnas.1000087107.
    1. Yang B., Xiao L., Liu S., Liu X., Luo Y., Ji Q., Yang P., Liu Z. Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice. Am. J. Transl. Res. 2017;9:376–385.
    1. Shobar R.M., Velineni S., Keshavarzian A., Swanson G., DeMeo M.T., Melson J.E., Losurdo J., Engen P.A., Sun Y., Koenig L., Mutlu E.A. The Effects of Bowel Preparation on Microbiota-Related Metrics Differ in Health and in Inflammatory Bowel Disease and for the Mucosal and Luminal Microbiota Compartments. Clin. Transl. Gastroenterol. 2016;7:e143. doi: 10.1038/ctg.2015.54.
    1. Kajiura T., Takeda T., Sakata S., Sakamoto M., Hashimoto M., Suzuki H., Suzuki M., Benno Y. Change of intestinal microbiota with elemental diet and its impact on therapeutic effects in a murine model of chronic colitis. Dig. Dis. Sci. 2009;54:1892–1900. doi: 10.1007/s10620-008-0574-6.
    1. Whelan K., Judd P.A., Preedy V.R., Simmering R., Jann A., Taylor M.A. Fructooligosaccharides and fiber partially prevent the alterations in fecal microbiota and short-chain fatty acid concentrations caused by standard enteral formula in healthy humans. J. Nutr. 2005;135:1896–1902.
    1. Harvey R.B., Andrews K., Droleskey R.E., Kansagra K.V., Stoll B., Burrin D.G., Sheffield C.L., Anderson R.C., Nisbet D.J. Qualitative and quantitative comparison of gut bacterial colonization in enterally and parenterally fed neonatal pigs. Curr. Issues Intest. Microbiol. 2006;7:61–64.
    1. Stephen A.M., Wiggins H.S., Cummings J.H. Effect of changing transit time on colonic microbial metabolism in man. Gut. 1987;28:601–609. doi: 10.1136/gut.28.5.601.
    1. Nagalingam N.A., Lynch S.V. Role of the microbiota in inflammatory bowel diseases. Inflamm. Bowel Dis. 2012;18:968–984. doi: 10.1002/ibd.21866.
    1. Frank D.N., Robertson C.E., Hamm C.M., Kpadeh Z., Zhang T., Chen H., Zhu W., Sartor R.B., Boedeker E.C., Harpaz N., et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm. Bowel Dis. 2011;17:179–184. doi: 10.1002/ibd.21339.
    1. Sartor R.B. The intestinal microbiota in inflammatory bowel diseases. Nestle Nutr. Inst. Workshop Ser. 2014;79:29–39. doi: 10.1159/000360674.
    1. Cuív P.Ó., Begun J., Keely S., Lewindon P.J., Morrison M. Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn’s disease. Food Funct. 2016;7:1741–1751. doi: 10.1039/C5FO01196E.
    1. Sasaki M., Sitaraman S.V., Babbin B.A., Gerner-Smidt P., Ribot E.M., Garrett N., Alpern J.A., Akyildiz A., Theiss A.L., Nusrat A., Klapproth J.M. Invasive Escherichia coli are a feature of Crohn’s disease. Lab. Investig. 2007;87:1042–1054. doi: 10.1038/labinvest.3700661.
    1. Rolhion N., Darfeuille-Michaud A. Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm. Bowel Dis. 2007;13:1277–1283. doi: 10.1002/ibd.20176.
    1. Martinez-Medina M., Aldeguer X., Lopez-Siles M., González-Huix F., López-Oliu C., Dahbi G., Blanco J.E., Blanco J., Garcia-Gil L.J., Darfeuille-Michaud A. Molecular diversity of Escherichia coli in the human gut: New ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn’s disease. Inflamm. Bowel Dis. 2009;15:872–878. doi: 10.1002/ibd.20860.

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