Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications

Foods - Tập 8 Số 3 - Trang 92
Dorna Davani-Davari1, Manica Negahdaripour2,3, Iman Karimzadeh4, Mostafa Seifan5, Milad Mohkam6, Seyed Jalil Masoumi7, Aydin Berenjian5, Younes Ghasemi8,2,7,3
1Pharmaceutical Biotechnology Incubator, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran;
2Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran;
3Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran
4Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71348, Iran;
5Faculty of Science and Engineering, University of Waikato, Hamilton 3216, New Zealand;
6Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71348, Iran;
7Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz 71348, Iran; J.
8Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 71348, Iran

Tóm tắt

Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.

Từ khóa


Tài liệu tham khảo

Collins, S., and Reid, G. (2016). Distant site effects of ingested prebiotics. Nutrients, 8.

Louis, P., Flint, H.J., and Michel, C. (2016). How to manipulate the microbiota: Prebiotics. Microbiota of the Human Body, Springer.

Walker, 2011, Dominant and diet-responsive groups of bacteria within the human colonic microbiota, ISME J., 5, 220, 10.1038/ismej.2010.118

Glenn, 1995, Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics, J. Nutr., 125, 1401, 10.1093/jn/125.6.1401

Gibson, 2004, Dietary modulation of the human colonic microbiota: Updating the concept of prebiotics, Nutr. Res. Rev., 17, 259, 10.1079/NRR200479

Bouhnik, 2004, The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: A double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study, Am. J. Clin. Nutr., 80, 1658, 10.1093/ajcn/80.6.1658

Flint, 2012, The role of the gut microbiota in nutrition and health, Nat. Rev. Gastroenterol. Hepatol., 9, 577, 10.1038/nrgastro.2012.156

Turroni, 2014, Molecular dialogue between the human gut microbiota and the host: A lactobacillus and bifidobacterium perspective, Cell. Mol. Life Sci., 71, 183, 10.1007/s00018-013-1318-0

Roberfroid, M. (1997). Health benefits of non-digestible oligosaccharides. Dietary Fiber in Health and Disease, Springer.

Morowvat, 2015, Probiotic potential of five lactobacillus strains isolated from traditional persian yoghurt in fars province, iran: Viewing through the window of phylogenetics, Biosci. Biotechnol. Res. Asia, 12, 1265, 10.13005/bbra/1780

Shokri, 2018, The inhibition effect of lactobacilli against growth and biofilm formation of pseudomonas aeruginosa, Probiot. Antimicrob. Proteins, 10, 34, 10.1007/s12602-017-9267-9

Stinson, 2017, Planting the seed: Origins, composition, and postnatal health significance of the fetal gastrointestinal microbiota, Crit. Rev. Microbiol., 43, 352, 10.1080/1040841X.2016.1211088

Trompette, 2014, Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis, Nat. Med., 20, 159, 10.1038/nm.3444

Hernot, 2009, In vitro fermentation profiles, gas production rates, and microbiota modulation as affected by certain fructans, galactooligosaccharides, and polydextrose, J. Agric. Food Chem., 57, 1354, 10.1021/jf802484j

Zhou, 2013, Starch structure modulates metabolic activity and gut microbiota profile, Anaerobe, 24, 71, 10.1016/j.anaerobe.2013.09.012

Clarke, 2010, Recognition of peptidoglycan from the microbiota by nod1 enhances systemic innate immunity, Nat. Med., 16, 228, 10.1038/nm.2087

Hamer, 2008, Review article: The role of butyrate on colonic function, Aliment. Pharmacol. Ther., 27, 104, 10.1111/j.1365-2036.2007.03562.x

Groen, 2013, The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism, J. Lipid Res., 54, 2325, 10.1194/jlr.R036012

Gibson, 2010, Dietary prebiotics: Current status and new definition, Food Sci. Technol. Bull. Funct. Foods, 7, 1, 10.1616/1476-2137.15880

Howlett, 2010, The definition of dietary fiber-discussions at the ninth vahouny fiber symposium: Building scientific agreement, Food Nutr. Res., 54, 5750, 10.3402/fnr.v54i0.5750

Slavin, 2013, Fiber and prebiotics: Mechanisms and health benefits, Nutrients, 5, 1417, 10.3390/nu5041417

Roberfroid, M.B. (2008). Prebiotics: Concept, definition, criteria, methodologies, and products. Handbook of Prebiotics, CRC Press.

Bindels, 2015, Towards a more comprehensive concept for prebiotics, Nat. Rev. Gastroenterol. Hepatol., 12, 303, 10.1038/nrgastro.2015.47

Scott, 2013, The influence of diet on the gut microbiota, Pharmacol. Res., 69, 52, 10.1016/j.phrs.2012.10.020

Hutkins, 2016, Prebiotics: Why definitions matter, Curr. Opin. Biotechnol., 37, 1, 10.1016/j.copbio.2015.09.001

Scott, 2014, Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro, FEMS Microbiol. Ecol., 87, 30, 10.1111/1574-6941.12186

Macfarlane, 2008, Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics, J. Appl. Microbiol., 104, 305

Johnson, 2013, Lentil (lens culinaris l.): A prebiotic-rich whole food legume, Food Res. Int., 51, 107, 10.1016/j.foodres.2012.11.025

Whelan, 2013, Mechanisms and effectiveness of prebiotics in modifying the gastrointestinal microbiota for the management of digestive disorders, Proc. Nutr. Soc., 72, 288, 10.1017/S0029665113001262

Sendra, 2011, Resistant starch as prebiotic: A review, Starch-Stärke, 63, 406, 10.1002/star.201000099

Ze, 2012, Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon, ISME J., 6, 1535, 10.1038/ismej.2012.4

Costabile, 2012, Impact of polydextrose on the faecal microbiota: A double-blind, crossover, placebo-controlled feeding study in healthy human subjects, Br. J. Nutr., 108, 471, 10.1017/S0007114511005782

Yoo, 2012, Plant cell wall polysaccharides as potential resources for the development of novel prebiotics, Biomol. Ther., 20, 371, 10.4062/biomolther.2012.20.4.371

Alonso, 2013, Pectic oligosaccharides: Manufacture and functional properties, Trends Food Sci. Technol., 30, 153, 10.1016/j.tifs.2013.01.006

Tzounis, 2011, Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study, Am. J. Clin. Nutr., 93, 62, 10.3945/ajcn.110.000075

Varzakas, T., Kandylis, P., Dimitrellou, D., Salamoura, C., Zakynthinos, G., and Proestos, C. (2018). Innovative and fortified food: Probiotics, prebiotics, gmos, and superfood. Preparation and Processing of Religious and Cultural Foods, Elsevier.

Ismail, 2013, Prebiotics as functional foods: A review, J. Funct Foods, 5, 1542, 10.1016/j.jff.2013.08.009

Panesar, 2013, Biotechnological approaches for the production of prebiotics and their potential applications, Crit. Rev. Biotechnol., 33, 345, 10.3109/07388551.2012.709482

Havenaar, 1999, Inulin: Fermentation and microbial ecology in the intestinal tract, Food Rev. Int., 15, 109, 10.1080/87559129909541179

Sangeetha, 2005, Recent trends in the microbial production, analysis and application of fructooligosaccharides, Trends Food Sci. Technol., 16, 442, 10.1016/j.tifs.2005.05.003

Yun, 1996, Fructooligosaccharides—Occurrence, preparation, and application, Enzym. Microb. Technol., 19, 107, 10.1016/0141-0229(95)00188-3

Prapulla, 2000, Microbial production of oligosaccharides: A review, Adv. Appl. Microbiol., 47, 299, 10.1016/S0065-2164(00)47008-5

Barreteau, 2006, Production of oligosaccharides as promising new food additive generation, Food Technol. Biotechnol., 44, 323

Caicedo, 2009, Semibatch and continuous fructooligosaccharides production by aspergillus sp. N74 in a mechanically agitated airlift reactor, J. Chem. Technol. Biotechnol., 84, 650, 10.1002/jctb.2095

Sangeetha, 2004, Production of fructo-oligosaccharides by fructosyl transferase from aspergillus oryzae cfr 202 and aureobasidium pullulans cfr 77, Process Biochem., 39, 755, 10.1016/S0032-9592(03)00186-9

Mohkam, M., Nezafat, N., Berenjian, A., Negahdaripour, M., Behfar, A., and Ghasemi, Y. (2016). Role of bacillus genus in the production of value-added compounds. Bacilli and Agrobiotechnology, Springer.

Chen, 1996, Production of β-fructofuranosidase by aspergillus japonicus, Enzym. Microb. Technol., 18, 153, 10.1016/0141-0229(95)00099-2

Prata, 2010, Fructooligosaccharide production by penicillium expansum, Biotechnol. Lett., 32, 837, 10.1007/s10529-010-0231-y

Maiorano, 2008, Microbial production of fructosyltransferases for synthesis of pre-biotics, Biotechnol. Lett., 30, 1867, 10.1007/s10529-008-9793-3

Mussatto, 2009, Fructooligosaccharides and β-fructofuranosidase production by aspergillus japonicus immobilized on lignocellulosic materials, J. Mol. Catal. B Enzym., 59, 76, 10.1016/j.molcatb.2009.01.005

Jong, 1993, The production of high-content fructo-oligosaccharides from sucrose by the mixed-enzyme system of fructosyltransferase and glucose oxidase, Biotechnol. Lett., 15, 573, 10.1007/BF00138542

Sheu, 2002, Continuous production of high-content fructooligosaccharides by a complex cell system, Biotechnol. Prog., 18, 1282, 10.1021/bp020081y

Yun, 1994, Batch production of high-content fructo-oligosaccharides from sucrose by the mixed-enzyme system of β-fructofuranosidase and glucose oxidase, J. Ferment. Bioeng., 77, 159, 10.1016/0922-338X(94)90316-6

Lin, 2008, High-content fructooligosaccharides production using two immobilized microorganisms in an internal-loop airlift bioreactor, J. Chin. Inst. Chem. Eng., 39, 211, 10.1016/j.jcice.2008.01.006

Nishizawa, 2001, Kinetic study on transfructosylation by. Beta.-fructofuranosidase from aspergillus niger atcc 20611 and availability of a membrane reactor for fructooligosaccharide production, Food Sci. Technol. Res., 7, 39, 10.3136/fstr.7.39

Crittenden, 2002, Purification of food-grade oligosaccharides using immobilised cells of zymomonas mobilis, Appl. Microbiol. Biotechnol., 58, 297, 10.1007/s00253-001-0886-3

Goulas, 2007, Development of a process for the production and purification of α-and β-galactooligosaccharides from bifidobacterium bifidum ncimb 41171, Int. Dairy J., 17, 648, 10.1016/j.idairyj.2006.08.010

Olano, 2009, Comparison of fractionation techniques to obtain prebiotic galactooligosaccharides, Int. Dairy J., 19, 531, 10.1016/j.idairyj.2009.03.002

Yoon, 2003, Specificity of yeast (saccharomyces cerevisiae) in removing carbohydrates by fermentation, Carbohydr. Res., 338, 1127, 10.1016/S0008-6215(03)00097-1

Palcic, 1999, Biocatalytic synthesis of oligosaccharides, Curr. Opin. Biotechnol., 10, 616, 10.1016/S0958-1669(99)00044-0

Weijers, 2008, Glycosyltransferase-catalyzed synthesis of bioactive oligosaccharides, Biotechnol. Adv., 26, 436, 10.1016/j.biotechadv.2008.05.001

Koizumi, 1998, Large-scale production of udp-galactose and globotriose by coupling metabolically engineered bacteria, Nat. Biotechnol., 16, 847, 10.1038/nbt0998-847

Albermann, 2001, Synthesis of the milk oligosaccharide 2′-fucosyllactose using recombinant bacterial enzymes, Carbohydr. Res., 334, 97, 10.1016/S0008-6215(01)00177-X

Priem, 2002, A new fermentation process allows large-scale production of human milk oligosaccharides by metabolically engineered bacteria, Glycobiology, 12, 235, 10.1093/glycob/12.4.235

Monsan, 1995, Enzymatic synthesis of oligosaccharides, FEMS Microbiol. Rev., 16, 187, 10.1111/j.1574-6976.1995.tb00165.x

Osman, 2012, Bbgiv is an important bifidobacterium β-galactosidase for the synthesis of prebiotic galactooligosaccharides at high temperatures, J. Agric. Food Chem., 60, 740, 10.1021/jf204719w

Prenosil, 1987, Formation of oligosaccharides during enzymatic lactose: Part i: State of art, Biotechnol. Bioeng., 30, 1019, 10.1002/bit.260300904

Rabiu, 2001, Synthesis and fermentation properties of novel galacto-oligosaccharides by β-galactosidases frombifidobacterium species, Appl. Environ. Microbiol., 67, 2526, 10.1128/AEM.67.6.2526-2530.2001

Zarate, 1990, Oligosaccharide formation during enzymatic lactose hydrolysis: A literature review, J. Food Prot., 53, 262, 10.4315/0362-028X-53.3.262

Neri, 2009, Galacto-oligosaccharides production during lactose hydrolysis by free aspergillus oryzae β-galactosidase and immobilized on magnetic polysiloxane-polyvinyl alcohol, Food Chem., 115, 92, 10.1016/j.foodchem.2008.11.068

Iqbal, 2010, Β-galactosidase from lactobacillus plantarum wcfs1: Biochemical characterization and formation of prebiotic galacto-oligosaccharides, Carbohydr. Res., 345, 1408, 10.1016/j.carres.2010.03.028

Iqbal, 2011, Characterization of a heterodimeric gh2 β-galactosidase from lactobacillus sakei lb790 and formation of prebiotic galacto-oligosaccharides, J. Agric. Food Chem., 59, 3803, 10.1021/jf103832q

Yi, 2011, Overexpression and characterization of a novel transgalactosylic and hydrolytic β-galactosidase from a human isolate bifidobacterium breve b24, New Biotechnol., 28, 806, 10.1016/j.nbt.2011.07.006

Fukuda, 2008, Whole-cell biocatalysts for biodiesel fuel production, Trends Biotechnol., 26, 668, 10.1016/j.tibtech.2008.08.001

Burton, 2002, The search for the ideal biocatalyst, Nat. Biotechnol., 20, 37, 10.1038/nbt0102-37

Schmid, 2001, Industrial biocatalysis today and tomorrow, Nature, 409, 258, 10.1038/35051736

Onishi, 1996, Gluco-oligosaccharide and galacto-oligosaccharide production by rhodotorula minuta ifo879, J. Ferment. Bioeng., 82, 124, 10.1016/0922-338X(96)85033-1

Onishi, 1995, Production of galacto-oligosaccharide from lactose by sterigmatomyces elviae cbs8119, Appl. Environ. Microbiol., 61, 4022, 10.1128/aem.61.11.4022-4025.1995

Onishi, 1996, Galacto-oligosaccharide production from lactose by sirobasidium magnum cbs6803, Lett. Appl. Microbiol., 23, 253, 10.1111/j.1472-765X.1996.tb00077.x

Onishi, 1996, Purification and properties of a galacto-and gluco-oligosaccharide-producing β-glycosidase from rhodotorula minuta ifo879, J. Ferment. Bioeng., 82, 439, 10.1016/S0922-338X(97)86979-6

Onishi, 1997, Purification and characterization of galacto-oligosaccharide-producing β-galactosidase from sirobasidium magnum, Lett. Appl. Microbiol., 24, 82, 10.1046/j.1472-765X.1997.00351.x

Li, 2009, Cell surface engineering of a β-galactosidase for galactooligosaccharide synthesis, Appl. Environ. Microbiol., 75, 5938, 10.1128/AEM.00326-09

Osman, 2010, A comprehensive investigation of the synthesis of prebiotic galactooligosaccharides by whole cells of bifidobacterium bifidum ncimb 41171, J. Biotechnol., 150, 140, 10.1016/j.jbiotec.2010.08.008

Ji, 2005, Galacto-oligosaccharide production by a thermostable recombinant β-galactosidase from thermotoga maritima, World J. Microbiol. Biotechnol., 21, 759, 10.1007/s11274-004-5487-8

Terpe, 2006, Overview of bacterial expression systems for heterologous protein production: From molecular and biochemical fundamentals to commercial systems, Appl. Microbiol. Biotechnol., 72, 211, 10.1007/s00253-006-0465-8

Demain, 2009, Production of recombinant proteins by microbes and higher organisms, Biotechnol. Adv., 27, 297, 10.1016/j.biotechadv.2009.01.008

Yin, 2007, Select what you need: A comparative evaluation of the advantages and limitations of frequently used expression systems for foreign genes, J. Biotechnol., 127, 335, 10.1016/j.jbiotec.2006.07.012

Porro, 2005, Recombinant protein production in yeasts, Mol. Biotechnol., 31, 245, 10.1385/MB:31:3:245

Buckholz, 1991, Yeast systems for the commercial production of heterologous proteins, Nat. Biotechnol., 9, 1067, 10.1038/nbt1191-1067

Flint, 2007, Interactions and competition within the microbial community of the human colon: Links between diet and health, Environ. Microbiol., 9, 1101, 10.1111/j.1462-2920.2007.01281.x

Cecchini, D.A., Laville, E., Laguerre, S., Robe, P., Leclerc, M., Doré, J., Henrissat, B., Remaud-Siméon, M., Monsan, P., and Potocki-Véronèse, G. (2013). Functional metagenomics reveals novel pathways of prebiotic breakdown by human gut bacteria. PLoS ONE, 8.

Belenguer, 2006, Two routes of metabolic cross-feeding between bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut, Appl. Environ. Microbiol., 72, 3593, 10.1128/AEM.72.5.3593-3599.2006

Ryan, 2006, Screening for and identification of starch-, amylopectin-, and pullulan-degrading activities in bifidobacterial strains, Appl. Environ. Microbiol., 72, 5289, 10.1128/AEM.00257-06

Rossi, 2005, Fermentation of fructooligosaccharides and inulin by bifidobacteria: A comparative study of pure and fecal cultures, Appl. Environ. Microbiol., 71, 6150, 10.1128/AEM.71.10.6150-6158.2005

Falony, 2006, Cross-feeding between bifidobacterium longum bb536 and acetate-converting, butyrate-producing colon bacteria during growth on oligofructose, Appl. Environ. Microbiol., 72, 7835, 10.1128/AEM.01296-06

Walker, 2005, Ph and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon, Appl. Environ. Microbiol., 71, 3692, 10.1128/AEM.71.7.3692-3700.2005

Duncan, 2009, The role of ph in determining the species composition of the human colonic microbiota, Environ. Microbiol., 11, 2112, 10.1111/j.1462-2920.2009.01931.x

Wilson, 2017, Prebiotic inulin-type fructans and galacto-oligosaccharides: Definition, specificity, function, and application in gastrointestinal disorders, J. Gastroenterol. Hepatol., 32, 64, 10.1111/jgh.13700

Hunter, 1999, Controlled trial of oligofructose in the management of irritable bowel syndrome, J. Nutr., 129, 1451S, 10.1093/jn/129.7.1451S

Olesen, 2000, Efficacy, safety, and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome, Am. J. Clin. Nutr., 72, 1570, 10.1093/ajcn/72.6.1570

Paineau, 2008, The effects of regular consumption of short-chain fructo-oligosaccharides on digestive comfort of subjects with minor functional bowel disorders, Br. J. Nutr., 99, 311, 10.1017/S000711450779894X

Silk, 2009, Clinical trial: The effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome, Aliment. Pharmacol. Ther., 29, 508, 10.1111/j.1365-2036.2008.03911.x

Lindsay, 2006, Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with crohn’s disease, Gut, 55, 348, 10.1136/gut.2005.074971

Benjamin, 2011, Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active crohn’s disease, Gut, 60, 923, 10.1136/gut.2010.232025

Joossens, 2011, Effect of oligofructose-enriched inulin (of-in) on bacterial composition and disease activity of patients with crohn’s disease: Results from a double-blinded randomised controlled trial, Gut, 61, 958, 10.1136/gutjnl-2011-300413

Candela, 2011, Human intestinal microbiota: Cross-talk with the host and its potential role in colorectal cancer, Crit. Rev. Microbiol., 37, 1, 10.3109/1040841X.2010.501760

Louis, 2009, Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine, FEMS Microbiol. Lett., 294, 1, 10.1111/j.1574-6968.2009.01514.x

Davis, 2009, Gastrointestinal microflora, food components and colon cancer prevention, J. Nutr. Biochem., 20, 743, 10.1016/j.jnutbio.2009.06.001

2005, Inulin-type fructans and reduction in colon cancer risk: Review of experimental and human data, Br. J. Nutr., 93, S73, 10.1079/BJN20041349

Rafter, 2007, Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients, Am. J. Clin. Nutr., 85, 488, 10.1093/ajcn/85.2.488

Patel, 2013, Therapeutic use of prebiotics, probiotics, and postbiotics to prevent necrotizing enterocolitis: What is the current evidence?, Clin. Perinatol., 40, 11, 10.1016/j.clp.2012.12.002

Knol, 2005, Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants, Acta Paediatr., 94, 31, 10.1111/j.1651-2227.2005.tb02152.x

Boehm, 2002, Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants, Arch. Dis. Childhood-Fetal Neonatal Ed., 86, F178, 10.1136/fn.86.3.F178

Kapiki, 2007, The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants, Early Hum. Dev., 83, 335, 10.1016/j.earlhumdev.2006.07.003

Indrio, 2009, Effects of probiotic and prebiotic on gastrointestinal motility in newborns, J. Physiol. Pharmacol., 60, 27

Indrio, 2009, Prebiotics improve gastric motility and gastric electrical activity in preterm newborns, J. Pediatr. Gastroenterol. Nutr., 49, 258, 10.1097/MPG.0b013e3181926aec

Labayen, 2001, Relationship between lactose digestion, gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption, Aliment. Pharmacol. Ther., 15, 543, 10.1046/j.1365-2036.2001.00952.x

Srinivasjois, 2009, Prebiotic supplementation of formula in preterm neonates: A systematic review and meta-analysis of randomised controlled trials, Clin. Nutr., 28, 237, 10.1016/j.clnu.2009.03.008

Klinder, 2004, Gut fermentation products of insulin-derived prebiotics beneficially modulate markers of tumour progression in human colon tumour cells, Int. J. Cancer Prev., 1, 19

Verghese, 2002, Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature fisher 344 rats, J. Nutr., 132, 2804, 10.1093/jn/132.9.2804

Denji, 2015, Effect of dietary prebiotic mannan oligosaccharide (mos) on growth performance, intestinal microflora, body composition, haematological and blood serum biochemical parameters of rainbow trout (oncorhynchus mykiss) juveniles, J. Fish. Aquat. Sci., 10, 255

Klatt, 2013, Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in siv-infected macaques, J. Clin. Investig., 123, 903

Langen, 2009, Prebiotics in chronic intestinal inflammation, Inflamm. Bowel Dis., 15, 454, 10.1002/ibd.20737

Steed, H., and Macfarlane, S. (2009). Mechanisms of prebiotic impact on health. Prebiotics and Probiotics Science and Technology, Springer.

Oyofo, 1989, Prevention of salmonella typhimurium colonization of broilers with d-mannose, Poult. Sci., 68, 1357, 10.3382/ps.0681357

Thorburn, 2014, Diet, metabolites, and “western-lifestyle” inflammatory diseases, Immunity, 40, 833, 10.1016/j.immuni.2014.05.014

Fujiwara, 2010, Maternal consumption of fructo-oligosaccharide diminishes the severity of skin inflammation in offspring of nc/nga mice, Br. J. Nutr., 103, 530, 10.1017/S000711450999198X

Shadid, 2007, Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity—A randomized, double-blind, placebo-controlled study, Am. J. Clin. Nutr., 86, 1426, 10.1093/ajcn/86.5.1426

Firmansyah, 2001, Improved humoral immune response to measles vaccine in infants receiving infant cereal with fructooligosaccharides, J. Pediatr. Gastroenterol. Nutr., 31, A521

Bender, 2004, Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors, J. Am. Geriatr. Soc., 52, 3, 10.1111/j.1532-5415.2004.52003.x

Lomax, 2012, Β2-1 fructans have a bifidogenic effect in healthy middle-aged human subjects but do not alter immune responses examined in the absence of an in vivo immune challenge: Results from a randomised controlled trial, Br. J. Nutr., 108, 1818, 10.1017/S0007114511007276

Saavedra, 1999, Gastro-intestinal function in infants consuming a weaning food supplemented with oligofructose, a prebiotic, J. Pediatr. Gastroenterol. Nutr., 29, 513

Tschernia, 1999, Effects of long-term consumption of a weaning food supplemented with oligofructose, a prebiotic, on general infant health status, J. Pediatr. Gastroenterol. Nutr., 29, 503

Clarke, 2016, Β2-1 fructan supplementation alters host immune responses in a manner consistent with increased exposure to microbial components: Results from a double-blinded, randomised, cross-over study in healthy adults, Br. J. Nutr., 115, 1748, 10.1017/S0007114516000908

Lomax, 2015, Inulin-type β2-1 fructans have some effect on the antibody response to seasonal influenza vaccination in healthy middle-aged humans, Front. Immunol., 6, 490, 10.3389/fimmu.2015.00490

Mosca, 2010, Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants, J. Allergy Clin. Immunol., 126, 791, 10.1016/j.jaci.2010.07.022

Moro, 2006, A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age, Arch. Dis. Childhood, 91, 814, 10.1136/adc.2006.098251

Guigoz, 2002, Effects of oligosaccharide on the faecal flora and non-specific immune system in elderly people, Nutr. Res., 22, 13, 10.1016/S0271-5317(01)00354-2

Vulevic, 2008, Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (b-gos) in healthy elderly volunteers, Am. J. Clin. Nutr., 88, 1438, 10.3945/ajcn.2008.26242

Vulevic, 2015, Influence of galacto-oligosaccharide mixture (b-gos) on gut microbiota, immune parameters and metabonomics in elderly persons, Br. J. Nutr., 114, 586, 10.1017/S0007114515001889

Kukkonen, 2007, Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial, J. Allergy Clin. Immunol., 119, 192, 10.1016/j.jaci.2006.09.009

Gaman, 2008, Neuromodulatory processes of the brain–gut axis, Neuromodulation, 11, 249, 10.1111/j.1525-1403.2008.00172.x

Mudd, 2016, Dietary prebiotics, milk fat globule membrane, and lactoferrin affects structural neurodevelopment in the young piglet, Front. Pediatr., 4, 4, 10.3389/fped.2016.00004

Grenham, 2011, Brain–gut–microbe communication in health and disease, Front. Physiol., 2, 94, 10.3389/fphys.2011.00094

Liu, 2015, Modulation of gut microbiota–brain axis by probiotics, prebiotics, and diet, J. Agric. Food Chem., 63, 7885, 10.1021/acs.jafc.5b02404

Forsythe, P., Bienenstock, J., and Kunze, W.A. (2014). Vagal pathways for microbiome-brain-gut axis communication. Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease, Springer.

Savignac, 2013, Prebiotic feeding elevates central brain derived neurotrophic factor, n-methyl-d-aspartate receptor subunits and d-serine, Neurochem. Int., 63, 756, 10.1016/j.neuint.2013.10.006

Williams, 2016, Neonatal prebiotic (bgos) supplementation increases the levels of synaptophysin, glun2a-subunits and bdnf proteins in the adult rat hippocampus, Synapse, 70, 121, 10.1002/syn.21880

Sudo, 2004, Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice, J. Physiol., 558, 263, 10.1113/jphysiol.2004.063388

Heijtz, 2011, Normal gut microbiota modulates brain development and behavior, Proc. Natl. Acad. Sci. USA, 108, 3047, 10.1073/pnas.1010529108

Neufeld, 2011, Reduced anxiety-like behavior and central neurochemical change in germ-free mice, Neurogastroenterol. Motil., 23, 255-e119, 10.1111/j.1365-2982.2010.01620.x

Nelson, 2012, Neurologic effects of exogenous saccharides: A review of controlled human, animal, and in vitro studies, Nutr. Neurosci., 15, 149, 10.1179/1476830512Y.0000000004

Best, 2015, Acute effects of a dietary non-starch polysaccharide supplement on cognitive performance in healthy middle-aged adults, Nutr. Neurosci., 18, 76, 10.1179/1476830513Y.0000000101

Best, 2009, Saccharide effects on cognition and well-being in middle-aged adults: A randomized controlled trial, Dev. Neuropsychol., 35, 66, 10.1080/87565640903325709

Han, 2010, Water extract of triticum aestivum l. And its components demonstrate protective effect in a model of vascular dementia, J. Med. Food, 13, 572, 10.1089/jmf.2009.1242

Schmidt, 2015, Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers, Psychopharmacology, 232, 1793, 10.1007/s00213-014-3810-0

Westerbeek, 2016, Neurodevelopment of preterm infants at 24 month after neonatal supplementation of a prebiotic mix: A randomized trial, J. Pediatr. Gastroenterol. Nutr., 63, 270, 10.1097/MPG.0000000000001148

Smith, 2015, An investigation of the acute effects of oligofructose-enriched inulin on subjective wellbeing, mood and cognitive performance, Nutrients, 7, 8887, 10.3390/nu7115441

Smith, 2005, The concept of well-being: Relevance to nutrition research, Br. J. Nutr., 93, S1, 10.1079/BJN20041351

Waworuntu, 2014, Dietary prebiotics improve memory and social interactions while reducing anxiety when provided early in life to normally developing rodents (637.5), FASEB J., 28, 637.5, 10.1096/fasebj.28.1_supplement.637.5

Messaoudi, 2005, Behavioural and cognitive effects of oligofructose-enriched inulin in rats, Br. J. Nutr., 93, S27, 10.1079/BJN20041348

Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with asds: A consensus report, Pediatrics, 125, S1, 10.1542/peds.2009-1878C

Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D., and Rubin, R.A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC Gastroenterol., 11.

Navarro, 2016, Can probiotics benefit children with autism spectrum disorders?, World J. Gastroenterol., 22, 10093, 10.3748/wjg.v22.i46.10093

De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS ONE, 8.

Wils, 2012, Impact of a resistant dextrin on intestinal ecology: How altering the digestive ecosystem with nutriose®, a soluble fibre with prebiotic properties, may be beneficial for health, J. Int. Med. Res., 40, 211, 10.1177/147323001204000122

Nankova, B.B., Agarwal, R., MacFabe, D.F., and La Gamma, E.F. (2014). Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including creb-dependent catecholaminergic neurotransmission, in pc12 cells-possible relevance to autism spectrum disorders. PLoS ONE, 9.

Guggenheim, 1966, Treatment of chronic portal-systemic encephalopathy with lactulose, Lancet, 287, 890, 10.1016/S0140-6736(66)91573-X

Prasad, 2007, Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy, Hepatology, 45, 549, 10.1002/hep.21533

Shukla, 2011, Meta-analysis: The effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy, Aliment. Pharmacol. Ther., 33, 662, 10.1111/j.1365-2036.2010.04574.x

Elkington, 1969, Lactulose in the treatment of chronic portal-systemic encephalopathy: A double-blind clinical trial, N. Engl. J. Med., 281, 408, 10.1056/NEJM196908212810803

Blanc, 1992, Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: Results of a meta-analysis, Hepatology, 15, 222, 10.1002/hep.1840150209

Fiorello, 1993, Lactitol in treatment of chronic hepatic encephalopathy, Digest. Dis. Sci., 38, 916, 10.1007/BF01295920

Weber, 1996, Lactulose and combination therapy of hepatic encephalopathy: The role of the intestinal microflora, Digest. Dis., 14, 53, 10.1159/000171583

Hong, 2015, Photoprotective effects of galacto-oligosaccharide and/or bifidobacterium longum supplementation against skin damage induced by ultraviolet irradiation in hairless mice, Int. J. Food Sci. Nutr., 66, 923, 10.3109/09637486.2015.1088823

Kawakami, 2005, Dietary galacto-oligosaccharides mixture can suppress serum phenol and p-cresol levels in rats fed tyrosine diet, J. Nutr. Sci. Vitaminol., 51, 182, 10.3177/jnsv.51.182

Mitsuyoshi, 2013, Consecutive intake of fermented milk containing bifidobacterium breve strain yakult and galacto-oligosaccharides benefits skin condition in healthy adult women, Biosci. Microbiot. Food Health, 32, 33, 10.12938/bmfh.32.33

Miyazaki, 2013, Bifidobacterium fermented milk and galacto-oligosaccharides lead to improved skin health by decreasing phenols production by gut microbiota, Benef. Microbes, 5, 121, 10.3920/BM2012.0066

Mohkam, 2016, Identification of bacillus probiotics isolated from soil rhizosphere using 16s rrna, reca, rpob gene sequencing and rapd-pcr, Probiot. Antimicrob. Proteins, 8, 8, 10.1007/s12602-016-9208-z

Mohkam, 2016, Characterization and in vitro probiotic assessment of potential indigenous bacillus strains isolated from soil rhizosphere, Minerva Biotechnol., 28, 19

Mozaffarian, 2015, Aha statistical update, Heart Dis. Stroke, 131, 29

Letexier, 2003, Addition of inulin to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans, Am. J. Clin. Nutr., 77, 559, 10.1093/ajcn/77.3.559

Russo, 2008, Inulin-enriched pasta affects lipid profile and lp (a) concentrations in italian young healthy male volunteers, Eur. J. Nutr., 47, 453, 10.1007/s00394-008-0748-1

Forcheron, 2007, Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans, Metabolism, 56, 1093, 10.1016/j.metabol.2007.03.019

Vogt, 2006, L-rhamnose and lactulose decrease serum triacylglycerols and their rates of synthesis, but do not affect serum cholesterol concentrations in men, J. Nutr., 136, 2160, 10.1093/jn/136.8.2160

Jenkins, 1991, Specific types of colonic fermentation may raise low-density-lipoprotein-cholesterol concentrations, Am. J. Clin. Nutr., 54, 141, 10.1093/ajcn/54.1.141

Vulevic, 2013, A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults, J. Nutr., 143, 324, 10.3945/jn.112.166132

Tiwari, 2011, Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels, Nutrition, 27, 1008, 10.1016/j.nut.2010.11.006

Brighenti, 2007, Dietary fructans and serum triacylglycerols: A meta-analysis of randomized controlled trials, J. Nutr., 137, 2552S, 10.1093/jn/137.11.2552S

Beynen, 1982, The effects of lactate and acetate on fatty acid and cholesterol biosynthesis by isolated rat hepatocytes, Int. J. Biochem., 14, 165, 10.1016/0020-711X(82)90135-5

Wolever, 1989, Effect of rectal infusion of short chain fatty acids in human subjects, Am. J. Gastroenterol., 84, 1027

Wolever, 1995, Propionate inhibits incorporation of colonic [1, 2–13c] acetate into plasma lipids in humans, Am. J. Clin. Nutr., 61, 1241, 10.1093/ajcn/61.6.1241

Mortensen, 1988, Short-chain fatty acid production from mono-and disaccharides in a fecal incubation system: Implications for colonic fermentation of dietary fiber in humans, J. Nutr., 118, 321, 10.1093/jn/118.3.321

Lambert, J.E., Parnell, J.A., Eksteen, B., Raman, M., Bomhof, M.R., Rioux, K.P., Madsen, K.L., and Reimer, R.A. (2015). Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: A randomized controlled trial protocol. BMC Gastroenterol., 15.

Tarantino, 2015, Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease, Future Microbiol., 10, 889, 10.2217/fmb.15.13

Cashman, 2002, Calcium intake, calcium bioavailability and bone health, Br. J. Nutr., 87, S169, 10.1079/BJN/2002534

Carlson, 2018, Health effects and sources of prebiotic dietary fiber, Curr. Dev. Nutr., 2, nzy005, 10.1093/cdn/nzy005

Andersson, 1997, Inulin and oligofructose do not influence the absorption of cholesterol, or the excretion of cholesterol, ca, mg, zn, fe, or bile acids but increases energy excretion in ileostomy subjects, Eur. J. Clin. Nutr., 51, 1, 10.1038/sj.ejcn.1600320

Schaafsma, 1998, Nondigestible oligosaccharides do not interfere with calcium and nonheme-iron absorption in young, healthy men, Am. J. Clin. Nutr., 67, 445, 10.1093/ajcn/67.3.445

Tahiri, 2003, Effect of short-chain fructooligosaccharides on intestinal calcium absorption and calcium status in postmenopausal women: A stable-isotope study, Am. J. Clin. Nutr., 77, 449, 10.1093/ajcn/77.2.449

Teucher, 2006, Absorption of calcium from milks enriched with fructo-oligosaccharides, caseinophosphopeptides, tricalcium phosphate, and milk solids, Am. J. Clin. Nutr., 83, 310, 10.1093/ajcn/83.2.310

Muijs, 1999, Lactulose stimulates calcium absorption in postmenopausal women, J. Bone Miner. Res., 14, 1211, 10.1359/jbmr.1999.14.7.1211

Schoterman, 2000, Transgalactooligosaccharides stimulate calcium absorption in postmenopausal women, J. Nutr., 130, 2938, 10.1093/jn/130.12.2938

Abrams, 2005, A combination of prebiotic short-and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents, Am. J. Clin. Nutr., 82, 471, 10.1093/ajcn/82.2.471

Griffin, 2002, Non-digestible oligosaccharides and calcium absorption in girls with adequate calcium intakes, Br. J. Nutr., 87, S187, 10.1079/BJN/2002536

Svensson, U., and Håkansson, J. (2014). Safety of Food and Beverages: Safety of Probiotics and Prebiotics, Elsevier.

Garg, 2018, Physiological effects of prebiotics and its role in prevention of necrotizing enterocolitis in preterm neonates, J. Matern.-Fetal Neonatal Med., 31, 2071, 10.1080/14767058.2017.1332041

Tsai, 2019, Probiotics, prebiotics and amelioration of diseases, J. Biomed. Sci., 26, 3, 10.1186/s12929-018-0493-6