The Effect of Oligofructose-Enriched Inulin on Faecal Bacterial Counts and Microbiota-Associated Characteristics in Celiac Disease Children Following a Gluten-Free Diet: Results of a Randomized, Placebo-Controlled Trial

Natalia Drabińska, Elżbieta Jarocka-Cyrta, Lidia Hanna Markiewicz, Urszula Krupa-Kozak, Natalia Drabińska, Elżbieta Jarocka-Cyrta, Lidia Hanna Markiewicz, Urszula Krupa-Kozak

Abstract

Celiac disease (CD) is associated with intestinal microbiota alterations. The administration of prebiotics could be a promising method of restoring gut homeostasis in CD. The aim of this study was to evaluate the effect of prolonged oligofructose-enriched inulin (Synergy 1) administration on the characteristics and metabolism of intestinal microbiota in CD children following a gluten-free diet (GFD). Thirty-four paediatric CD patients (mean age 10 years; 62% females) on a GFD were randomized into two experimental groups receiving Synergy 1 (10 g/day) or placebo (maltodextrin; 7 g/day) for 3 months. The quantitative gut microbiota characteristics and short-chain fatty acids (SCFAs) concentration were analysed. In addition, side effects were monitored. Generally, the administration of Synergy 1 in a GFD did not cause any side effects. After the intervention period, Bifidobacterium count increased significantly (p < 0.05) in the Synergy 1 group. Moreover, an increase in faecal acetate and butyrate levels was observed in the prebiotic group. Consequently, total SCFA levels were 31% higher than at the baseline. The presented trial shows that Synergy 1 applied as a supplement of a GFD had a moderate effect on the qualitative characteristics of faecal microbiota, whereas it stimulated the bacterial metabolite production in CD children.

Keywords: celiac disease; gluten-free diet; gut microbiota; inulin; prebiotic; short-chain fatty acids.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Quantitative characteristics of faecal microbiota before (T0) and after (T1) the intervention, expressed by means ± SEM (standard error of the mean) and by log cells/g of faeces. * p < 0.05. TBN: total bacterial counts; BIF: Bifidobacterium sp.; Clept: C. leptum; BPP: Bacteroides-Prevotella-Porphyromonas; Ccocc: Clostridium coccoides; LAC: Lactobacillus sp.

References

    1. O’Hara A.M., Shanahan F. Gut Microbiota: Mining for Therapeutic Potential. Clin. Gastroenterol. Hepatol. 2007;5:274–284. doi: 10.1016/j.cgh.2006.12.009.
    1. Jandhyala S.M., Talukdar R., Subramanyam C., Vuyyuru H., Sasikala M., Reddy D.N. Role of the normal gut microbiota. World J. Gastroenterol. 2015;21:8836–8847. doi: 10.3748/wjg.v21.i29.8787.
    1. Leonard M.M., Fasano A. The microbiome as a possible target to prevent celiac disease. Expert Rev. Gastroenterol. Hepatol. 2016;10:555–556. doi: 10.1586/17474124.2016.1166954.
    1. Gujral N., Freeman H.J., Thomson A.B.R. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment. World J. Gastroenterol. 2012;18:6036–6059. doi: 10.3748/wjg.v18.i42.6036.
    1. Marasco G., di Biase A.R., Schiumerini R., Eusebi L.H., Iughetti L., Ravaioli F., Scaioli E., Colecchia A., Festi D. Gut microbiota and celiac disease. Dig. Dis. Sci. 2016;61:1461–1472. doi: 10.1007/s10620-015-4020-2.
    1. Di Cagno R., de Angelis M., de Pasquale I., Ndagijimana M., Vernocchi P., Ricciuti P., Gagliardi F., Laghi L., Crecchio C., Guerzoni M., et al. Duodenal and faecal microbiota of celiac children: Molecular, phenotype and metabolome characterization. BMC Microbiol. 2011;11:219. doi: 10.1186/1471-2180-11-219.
    1. Nistal E., Caminero A., Vivas S., Ruiz de Morales J.M., Sáenz de Miera L.E., Rodríguez-Aparicio L.B., Casqueiro J. Differences in faecal bacteria populations and faecal bacteria metabolism in healthy adults and celiac disease patients. Biochimie. 2012;94:1724–1729. doi: 10.1016/j.biochi.2012.03.025.
    1. Sanz Y., Sánchez E., Marzotto M., Calabuig M., Torriani S., Dellaglio F. Differences in faecal bacterial communities in coeliac and healthy children as detected by PCR and denaturing gradient gel electrophoresis. FEMS Immunol. Med. Microbiol. 2007;51:562–568. doi: 10.1111/j.1574-695X.2007.00337.x.
    1. De Palma G., Nadal I., Medina M., Donat E., Ribes-Koninckx C., Calabuig M., Sanz Y. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 2010;10:63. doi: 10.1186/1471-2180-10-63.
    1. Ilus T., Kaukinen K., Virta L.J., Pukkala E., Collin P. Incidence of malignancies in diagnosed celiac patients: A population-based estimate. Am. J. Gastroenterol. 2014;109:1471–1477. doi: 10.1038/ajg.2014.194.
    1. Tjellström B., Stenhammar L., Högberg L., Fälth-Magnusson K., Magnusson K.E., Midtvedt T., Sundqvist T., Norin E. Gut microflora associated characteristics in children with celiac disease. Am. J. Gastroenterol. 2005;100:2784–2788. doi: 10.1111/j.1572-0241.2005.00313.x.
    1. Tjellström B., Stenhammar L., Sundqvist T., Fälth-Magnusson K., Hollén E., Magnusson K.E., Norin E., Midtvedt T., Högberg L. The effects of oats on the function of gut microflora in children with coeliac disease. Aliment. Pharmacol. Ther. 2014;39:1156–1160. doi: 10.1111/apt.12707.
    1. Morrison D.J., Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7:189–200. doi: 10.1080/19490976.2015.1134082.
    1. Leonard M.M., Sapone A., Catassi C., Fasano A. Celiac disease and nonceliac gluten sensitivity: A review. JAMA. 2017;318:647–656. doi: 10.1001/jama.2017.9730.
    1. Quagliariello A., Aloisio I., Bozzicionci N., Luiselli D., D’Auria G., Martinez-Priego L., Pérez-Villarroya D., Langerholc T., Primec M., Mičetić-Turk D., et al. Effect of bifidobacterium breve on the intestinal microbiota of coeliac children on a gluten free diet: A pilot study. Nutrients. 2016;8:660. doi: 10.3390/nu8100660.
    1. Gibson G.R., Hutkins R., Sanders M.E., Prescott S.L., Reimer R.A., Salminen S.J., Scott K., Stanton C., Swanson K.S., Cani P.D., et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2017 doi: 10.1038/nrgastro.2017.75.
    1. Gibson G.R., Roberfroid M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. J. Nutr. 1995;125:1401–1412.
    1. Wilson B., Whelan K. Prebiotic inulin-type fructans and galacto-oligosaccharides: Definition, specificity, function, and application in gastrointestinal disorders. J. Gastroenterol. Hepatol. 2017;32:64–68. doi: 10.1111/jgh.13700.
    1. Wong C., Harris P., Ferguson L. Potential benefits of dietary fibre intervention in inflammatory bowel disease. Int. J. Mol. Sci. 2016;17:919. doi: 10.3390/ijms17060919.
    1. Krupa-Kozak U., Drabińska N., Jarocka-Cyrta E. The effect of oligofructose-enriched inulin supplementation on gut microbiota, nutritional status and gastrointestinal symptoms in paediatric coeliac disease patients on a gluten-free diet: Study protocol for a pilot randomized controlled trial. Nutr. J. 2017;16 doi: 10.1186/s12937-017-0268-z.
    1. . [(accessed on 11 February 2018)]; Available online: .
    1. Fotschki J., Szyc A.M., Laparra J.M., Markiewicz L.H., Wróblewska B. Immune-modulating properties of horse milk administered to mice sensitized to cow milk. J. Dairy Sci. 2016;99:9395–9404. doi: 10.3168/jds.2016-11499.
    1. Fuller Z., Louis P., Mihajlovski A., Rungapamestry V., Ratcliffe B., Duncan A.J. Influence of cabbage processing methods and prebiotic manipulation of colonic microflora on glucosinolate breakdown in man. Br. J. Nutr. 2007;98:364–372. doi: 10.1017/S0007114507709091.
    1. Rinttilä T., Kassinen A., Malinen E., Krogius L., Palva A. Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J. Appl. Microbiol. 2004;97:1166–1177. doi: 10.1111/j.1365-2672.2004.02409.x.
    1. Shen J., Zhang B., Wei G., Pang X., Wei H., Li M., Zhang Y., Jia W., Zhao L. Molecular profiling of the Clostridium leptum subgroup in human fecal microflora by PCR-denaturing gradient gel electrophoresis and clone library analysis. Appl. Environ. Microbiol. 2006;72:5232–5238. doi: 10.1128/AEM.00151-06.
    1. Matsuki T., Watanabe K., Fujimoto J., Miyamoto Y., Takada T., Matsumoto K., Oyaizu H., Tanaka R. Development of 16S rRNA-gene-targeted group-specific primers for the detection and identification of predominant bacteria in human feces. Appl. Environ. Microbiol. 2002;68:5445–5451. doi: 10.1128/AEM.68.11.5445-5451.2002.
    1. Heilig H.G.H.J., Zoetendal E.G., Vaughan E.E., Marteau P., Akkermans A.D.L., de Vos W.M. Molecular diversity of Lactobacillus spp. and other lactic acid bacteria in the human intestine as determined by specific amplification of 16S ribosomal DNA. Appl. Environ. Microbiol. 2002;68:114–123. doi: 10.1128/AEM.68.1.114-123.2002.
    1. García-Villalba R., Giménez-Bastida J.A., García-Conesa M.T., Tomás-Barberán F.A., Carlos Espín J., Larrosa M. Alternative method for gas chromatography-mass spectrometry analysis of short-chain fatty acids in faecal samples. J. Sep. Sci. 2012;35:1906–1913. doi: 10.1002/jssc.201101121.
    1. McCalley D.V. Analysis of volatile fatty acids by capillary gas chromatography using on-column injection of aqueous solutions. J. High Resolut. Chromatogr. 1989;12:465–467. doi: 10.1002/jhrc.1240120710.
    1. Drabińska N., Zieliński H., Krupa-Kozak U. Technological benefits of inulin-type fructans application in gluten-free products—A review. Trends Food Sci. Technol. 2016;56 doi: 10.1016/j.tifs.2016.08.015.
    1. Salazar N., Dewulf E.M., Neyrinck A.M., Bindels L.B., Cani P.D., Mahillon J., de Vos W.M., Thissen J.P., Gueimonde M., de los Reyes-Gavilán C.G., et al. Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women. Clin. Nutr. 2015;34:501–507. doi: 10.1016/j.clnu.2014.06.001.
    1. Langlands S.J. Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut. 2004;53:1610–1616. doi: 10.1136/gut.2003.037580.
    1. Bouhnik Y., Raskine L., Champion K., Andrieux C., Penven S., Jacobs H., Simoneau G. Prolonged administration of low-dose inulin stimulates the growth of bifidobacteria in humans. Nutr. Res. 2007;27:187–193. doi: 10.1016/j.nutres.2007.01.013.
    1. Aloisio I., Santini C., Biavati B., Dinelli G., Cencič A., Chingwaru W., Mogna L., Di Gioia D. Characterization of Bifidobacterium spp. strains for the treatment of enteric disorders in newborns. Appl. Microbiol. Biotechnol. 2012;96:1561–1576. doi: 10.1007/s00253-012-4138-5.
    1. Klemenak M., Dolinšek J., Langerholc T., di Gioia D., Mičetić-Turk D. Administration of Bifidobacterium breve decreases the production of TNF-α in children with celiac disease. Dig. Dis. Sci. 2015;60:3386–3392. doi: 10.1007/s10620-015-3769-7.
    1. Medina M., de Palma G., Ribes-Koninckx C., Calabuig M., Sanz Y. Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients. J. Inflamm. 2008;5:19. doi: 10.1186/1476-9255-5-19.
    1. Peterson D.A., McNulty N.P., Guruge J.L., Gordon J.I. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe. 2007;2:328–339. doi: 10.1016/j.chom.2007.09.013.
    1. Tuohy K.M., Finlay R.K., Wynne A.G., Gibson G.R. A Human volunteer study on the prebiotic effects of HP-inulin—Faecal bacteria enumerated using fluorescent in situ hybridisation (FISH) Anaerobe. 2001;7:113–118. doi: 10.1006/anae.2001.0368.
    1. Sghir A., Gramet G., Suau A., Rochet V., Pochart P., Dore J. Quantification of bacterial groups within human fecal flora by oligonucleotide probe hybridization. Appl. Environ. Microbiol. 2000;66:2263–2266. doi: 10.1128/AEM.66.5.2263-2266.2000.
    1. Collins M.D., Lawson P.A., Willems A., Cordoba J.J., Fernandez-Garayzabal J., Garcia P., Cai J., Hippe H., Farrow J.A. The phylogeny of the genus Clostridium: Proposal of five new genera and eleven new species combinations. Int. J. Syst. Bacteriol. 1994;44:812–826. doi: 10.1099/00207713-44-4-812.
    1. Louis P., Flint H.J. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol. Lett. 2009;294:1–8. doi: 10.1111/j.1574-6968.2009.01514.x.
    1. Kabeerdoss J., Sankaran V., Pugazhendhi S., Ramakrishna B.S. Clostridium leptum group bacteria abundance and diversity in the fecal microbiota of patients with inflammatory bowel disease: A case-control study in India. BMC Gastroenterol. 2013;13:20. doi: 10.1186/1471-230X-13-20.
    1. Adebola O.O., Corcoran O., Morgan W.A. Synbiotics: The impact of potential prebiotics inulin, lactulose and lactobionic acid on the survival and growth of lactobacilli probiotics. J. Funct. Foods. 2014;10:75–84. doi: 10.1016/j.jff.2014.05.010.
    1. Krupa-Kozak U., Markiewicz L.H., Lamparski G., Juśkiewicz J. Administration of inulin-supplemented gluten-free diet modified calcium absorption and caecal microbiota in rats in a calcium-dependent manner. Nutrients. 2017;9 doi: 10.3390/nu9070702.
    1. Beaumont M., Portune K.J., Steuer N., Lan A., Cerrudo V., Audebert M., Dumont F., Mancano G., Khodorova N., Andriamihaja M., et al. Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: A randomized, parallel, double-blind trial in overweight humans. Am. J. Clin. Nutr. 2017;106:1005–1019. doi: 10.3945/ajcn.117.158816.
    1. Wu G.D., Compher C., Chen E.Z., Smith S.A., Shah R.D., Bittinger K., Chehoud C., Albenberg L.G., Nessel L., Gilroy E., et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut. 2016;65:63–72. doi: 10.1136/gutjnl-2014-308209.
    1. Fukuda S., Toh H., Hase K., Oshima K., Nakanishi Y., Yoshimura K., Tobe T., Clarke J.M., Topping D.L., Suzuki T., et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469:543–547. doi: 10.1038/nature09646.
    1. Tjellström B., Högberg L., Stenhammar L., Fälth-Magnusson K., Magnusson K., Norin E., Sundqvist T., Midtvedt T. Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year’s gluten-free diet. Microb. Ecol. Health Dis. 2013;24:1–5. doi: 10.3402/mehd.v24i0.20905.
    1. Richards J.L., Yap Y.A., McLeod K.H., Mackay C.R., Mariño E. Dietary metabolites and the gut microbiota: An alternative approach to control inflammatory and autoimmune diseases. Clin. Transl. Immunol. 2016;5:e82. doi: 10.1038/cti.2016.29.
    1. Nilsson U., Nyman M. Short-chain fatty acid formation in the hindgut of rats fed oligosaccharides varying in monomeric composition, degree of polymerisation and solubility. Br. J. Nutr. 2005;94:705. doi: 10.1079/BJN20051531.
    1. Kanauchi O., Andoh A., Iwanaga T., Fujiyama Y., Mitsuyama K., Toyonaga A., Bamba T. Germinated barley foodstuffs attenuate colonic mucosal damage and mucosal nuclear factor kappa B activity in a spontaneous colitis model. J. Gastroenterol. Hepatol. 1999;14:1173–1179. doi: 10.1046/j.1440-1746.1999.02025.x.
    1. Abela A.-G., Fava S. Does the level of bacterial exposure in early life impact the risk of Type 1 diabetes? Expert Rev. Clin. Immunol. 2013;9:695–697. doi: 10.1586/1744666X.2013.814410.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다