Effects of Fructans from Mexican Agave in Newborns Fed with Infant Formula: A Randomized Controlled Trial

Gabriel López-Velázquez, Minerva Parra-Ortiz, Ignacio De la Mora-De la Mora, Itzhel García-Torres, Sergio Enríquez-Flores, Miguel Angel Alcántara-Ortigoza, Ariadna González-Del Angel, José Velázquez-Aragón, Rosario Ortiz-Hernández, José Manuel Cruz-Rubio, Pablo Villa-Barragán, Carlos Jiménez-Gutiérrez, Pedro Gutiérrez-Castrellón, Gabriel López-Velázquez, Minerva Parra-Ortiz, Ignacio De la Mora-De la Mora, Itzhel García-Torres, Sergio Enríquez-Flores, Miguel Angel Alcántara-Ortigoza, Ariadna González-Del Angel, José Velázquez-Aragón, Rosario Ortiz-Hernández, José Manuel Cruz-Rubio, Pablo Villa-Barragán, Carlos Jiménez-Gutiérrez, Pedro Gutiérrez-Castrellón

Abstract

Background: The importance of prebiotics consumption is increasing all over the world due to their beneficial effects on health. Production of better prebiotics from endemic plants raises possibilities to enhance nutritional effects in vulnerable population groups. Fructans derived from Agave Plant have demonstrated their safety and efficacy as prebiotics in animal models. Recently, the safety in humans of two fructans obtained from Agave tequilana (Metlin(®) and Metlos(®)) was demonstrated.

Methods: This study aimed to demonstrate the efficacy as prebiotics of Metlin(®) and Metlos(®) in newborns of a randomized, double blind, controlled trial with a pilot study design. Biological samples were taken at 20 ± 7 days, and three months of age from healthy babies. Outcomes of efficacy include impact on immune response, serum ferritin, C-reactive protein, bone metabolism, and gut bacteria changes.

Results: There were differences statistically significant for the groups of infants fed only with infant formula and with formula enriched with Metlin(®) and Metlos(®).

Conclusions: Our results support the efficacy of Metlin(®) and Metlos(®) as prebiotics in humans, and stand the bases to recommend their consumption.

Trial registration: ClinicalTrials.gov, NCT 01251783.

Trial registration: ClinicalTrials.gov NCT01251783.

Keywords: breast milk; immune response; infant microbiota; soluble fiber.

Figures

Figure 1
Figure 1
Changes in the relative abundance of gut bacteria, according to the kind of feeding after three months of treatment. Data from total counts were taken as 100% to normalize all the other counts. Reference group of breast milk fed (a), and Groups 1, 2, 3, 4, and 5, (b–f), respectively.
Figure 2
Figure 2
Clostridium population changes after three months of age in the different groups of study.

References

    1. Roberfroid M.B. Prebiotics: Preferential substrates for specific germs? Am. J. Clin. Nutr. 2001;73:406S–409S.
    1. Palacio M.I., Etcheverría A.I., Manrique G.D. Fermentation by Lactobacillus paracasei of galactooligosaccharides and low-molecular weight carbohydrates extracted from squash (Curcubita. maxima) and lupin (Lupinus. albus) seeds. J. Microbiol. Biotech. Food Sci. 2014;3:329–332.
    1. Bornet F.R., Brouns F., Tashiro Y., Duvillier V. Nutritional aspects of short-chain fructooligosaccharides: Natural occurrence, chemistry, physiology and health implications. Dig. Liver Dis. 2002;34:S111–S120. doi: 10.1016/S1590-8658(02)80177-3.
    1. Roberfroid M.B., van Loo J.A.E., Gibson G.R. The bifidogenic nature of chicory inulin and its hydrolysis product. J. Nutr. 1998;128:11–19.
    1. Grimoud J., Durand H., Courtin C., Monsan P., Ouarné F., Theodorou V., Roques C. In vitro screening of probiotic lactic acid bacteria and prebiotic glucooligosaccharides to select effective synbiotics. Anaerobe. 2010;16:493–500. doi: 10.1016/j.anaerobe.2010.07.005.
    1. De Vrese M., Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv. Biochem. Eng. Biotechnol. 2008;111:1–66.
    1. Lasekan J., Baggs G., Acosta S., Mackey A. Soy protein-based infant formulas with supplemental fructooligosaccharides: Gastrointestinal tolerance and hydration status in newborn infants. Nutrients. 2015;7:3022–3037. doi: 10.3390/nu7043022.
    1. Koletzko B. Innovations in infant milk feeding: From the past to the future. Nestle Nutr. Workshop Ser. Pediatr. Program. 2010;66:1–17.
    1. Risk assessment on use of Lactobacillus rhamnosus (LGG) as an ingredient in infant formula and baby foods (II) [(accessed on 22 October 2015)]. Available online: .
    1. European Food Safety Authority Scientific opinion on the substantiation of a health claim related Immunofortis and strengthening of the baby’s immune system pursuant to Article 14 of Regulation (EC) No 1924/2006. EFSA J. 2010;8:1430.
    1. Garcia Mendoza A. Distribution of Agave (Agavaceae) in Mexico. [(accessed on 22 October 2015)]. Available online: .
    1. Praznik W., Löppert R., Cruz Rubio J.M., Zangger K., Huber A. Structure of fructo-oligosaccharides from leaves and stem of Agave tequilana Weber, var. azul. Carbohydr. Res. 2013;15:64–73. doi: 10.1016/j.carres.2013.08.025.
    1. Gomez E., Tuohy K.M., Gibson G.R., Klinder A., Costabile A. In vitro evaluation of the fermentation properties and potential prebiotic activity of Agave fructans. J. Appl. Microbiol. 2010;108:2114–2121.
    1. Cieslik E., Topolska K., Praznik W., Cruz Rubio J.M. Effect of Agave fructans on selected parameters of calcium metabolism and bone condition in rats. J. Aging Res. Clin. Prac. 2012;1:103–108.
    1. Gracia M.I., Tinoco M.M., Rivera H.M., Sanchez B.F., Tapia P.G., Altamirano L.M., Romero R.L., García O.L. Acute toxicity and genotoxic evaluation of Metlin® and Metlos® (Organic Agave Fructans) Food Nutr. Sci. 2013;4:106–112. doi: 10.4236/fns.2013.47A013.
    1. López-Velázquez G., Díaz-García L., Anzo A., Parra-Ortiz M., Llamosas-Gallardo B., Ortiz-Hernández A.A., Mancilla-Ramírez J., Cruz-Rubio J.M., Gutiérrez-Castrellón P. Safety of a dual potential prebiotic system from Mexican agave "Metlin® and Metlos®", incorporated to an infant formula for term newborn babies: A randomized controlled trial. Rev. Investig. Clin. 2013;65:483–490.
    1. Penders J., Thijs C., Vink C., Stelma F.F., Snijders B., Kummeling I., van den Brandt P.A., Stobberingh E.E. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118:511–521. doi: 10.1542/peds.2005-2824.
    1. Haarman M., Knol J. Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium. species in infants receiving a prebiotic infant formula. Appl. Environ. Microbiol. 2005;71:2318–2324. doi: 10.1128/AEM.71.5.2318-2324.2005.
    1. Gronlund M.M., Lehtonen O.P., Eerola E., Kero P. Fecal microflora in healthy infants born by different methods of delivery: Permanent changes in intestinal flora after cesarean delivery. J. Pediatr. Gastroenterol. Nutr. 1999;28:19–25. doi: 10.1097/00005176-199901000-00007.
    1. Haarman M., Knol J. Quantitative Real-Time PCR analysis of fecal Lactobacillus species in Infants receiving a prebiotic infant formula. Appl. Environ. Microbiol. 2006;72:2359–2365. doi: 10.1128/AEM.72.4.2359-2365.2006.
    1. Nakamura N., Gaskins H.R., Collier C.T., Nava G.M., Rai D., Petschow B., Russell W.M., Harris C., Mackie R.I., Wampler J.L., et al. Molecular ecological analysis of fecal bacterial populations from term infants fed formula supplemented with selected blends of prebiotics. Appl. Environ. Microbiol. 2009;75:1121–1128. doi: 10.1128/AEM.02359-07.
    1. Nadkarni M.A., Martin F.E., Jacques N.A., Hunter N. Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primer set. Microbiology. 2002;148:257–266. doi: 10.1099/00221287-148-1-257.
    1. Friedewald W.T., Fredrickson D.S. Estimation of concentration of low density lipoprotein cholesterol in plasma without use of ultracentrifuge. Clin. Chem. 1972;18:449–502.
    1. Harmsen H.J.M., Wildeboer-Veloo A.C.M., Raangs G.C., Wagendorp A.A., Klijn N., Bindels J.G., Welling G.W. Analysis of intestinal flora development in breast-fed and formula-fed infants using molecular identification and detection methods. J. Pediatr. Gastroenterol. Nutr. 2000;30:61–67. doi: 10.1097/00005176-200001000-00019.
    1. Huebner J., Wehling R.L., Hutkins R.W. Functional activity of commercial prebiotics. Int. Dairy J. 2007;17:770–775. doi: 10.1016/j.idairyj.2006.10.006.
    1. Goldsmith F., O'Sullivan A., Smilowitz J.T., Freeman S.L. Lactation and Intestinal Microbiota: How Early Diet Shapes the Infant Gut. J. Mammary Gland Biol. Neoplasia. 2015 doi: 10.1007/s10911-015-9335-2.
    1. Vulevic J., Rastall R.A., Gibson G.R. Developing a quantitative approach for determining the in vitro prebiotic potential of dietary oligosaccharides. FEMS Microbiol. Lett. 2004;236:153–159. doi: 10.1111/j.1574-6968.2004.tb09641.x.
    1. Costalos C., Kapiki A., Apostolou M., Papathoma E. The effect of a prebiotic supplemented formula on growth and stool microbiology of term infants. Early Hum. Dev. 2008;84:45–49. doi: 10.1016/j.earlhumdev.2007.03.001.
    1. Magne F., Hachelaf W., Suau A., Boudraa G., Bouziane-Nedjadi K., Rigottier-Gois L., Touhami M., Desjeux J., Pochart P. Effects on faecal microbiota of dietary and acidic oligosaccharides in children during partial formula feeding. J. Pediatr. Gastroenterol. Nutr. 2008;46:580–588. doi: 10.1097/MPG.0b013e318164d920.
    1. Stark P.L., Lee A. The bacterial colonization of the large bowel of pre-term low birth weight neonates. J. Hyg. 1982;89:59–67. doi: 10.1017/S0022172400070546.
    1. Moro G., Minoli I., Mosca M., Fanaro S., Jelinek J., Stahl B., Boehm G. Dosage related bifidogenic effects of galacto and fructooligosaccharides in formula-fed term infants. J. Pediatr. Gastroenterol. Nutr. 2002;34:291–295. doi: 10.1097/00005176-200203000-00014.
    1. Niers L.E., Hoekstra M.O., Timmerman H.M., van Uden N.O., de Graaf P.M., Smits H.H., Kimpen J.L., Rijkers G.T. Selection of probiotic bacteria for prevention of allergic diseases: Immunomodulation of neonatal dendritic cells. Clin. Exp. Immunol. 2007;149:344–352. doi: 10.1111/j.1365-2249.2007.03421.x.
    1. Kalliomäki M., Kirjavainen P., Eerola E., Kero P., Salminen S., Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J. Allergy Clin. Immunol. 2001;107:129–134. doi: 10.1067/mai.2001.111237.
    1. Ouwehand A.C., Isolauri E., He F., Hashimoto H., Benno Y., Salminen S. Differences in Bifidobacterium flora composition in allergic and healthy infants. J. Allergy Clin. Immunol. 2001;108:144–145. doi: 10.1067/mai.2001.115754.
    1. Scholtens P.A., Alliet P., Raes M., Alles M.S., Kroes H., Boehm G., Knippels L.M., Knol J., Vandenplas Y. Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. J. Nutr. 2008;138:1141–1147.
    1. Jin H.X., Wang R.S., Chen S.J., Wang A.P., Liu X.Y. Early and late Iron supplementation for low birth weight infants: A meta-analysis. Ital. J. Pediatr. 2015;14:16. doi: 10.1186/s13052-015-0121-y.
    1. Delzenne N.M., Neyrinck A.M., Cani P.D. Gut microbiota and metabolic disorders: How prebiotic can work? Br. J. Nutr. 2013;109:S81–S85. doi: 10.1017/S0007114512004047.
    1. Williams C.M., Jackson K.G. Inulin and oligofructose: Effects on lipid metabolism from human studies. Br. J. Nutr. 2002;87:S261–S264. doi: 10.1079/BJN/2002546.
    1. Rauchenzauner M., Schmid A., Heinz-Erian P., Kapelari K., Falkensammer G., Griesmacher A., Finkenstedt G., Högler W. Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J. Clin. Endocrinol. Metab. 2007;92:443–449. doi: 10.1210/jc.2006-1706.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する