Administration of a Multi-Strain Probiotic Product to Women in the Perinatal Period Differentially Affects the Breast Milk Cytokine Profile and May Have Beneficial Effects on Neonatal Gastrointestinal Functional Symptoms. A Randomized Clinical Trial

Maria Elisabetta Baldassarre, Antonio Di Mauro, Paola Mastromarino, Margherita Fanelli, Domenico Martinelli, Flavia Urbano, Daniela Capobianco, Nicola Laforgia, Maria Elisabetta Baldassarre, Antonio Di Mauro, Paola Mastromarino, Margherita Fanelli, Domenico Martinelli, Flavia Urbano, Daniela Capobianco, Nicola Laforgia

Abstract

Background: Probiotic supplementation to women during pregnancy and lactation can modulate breast milk composition, with immune benefits being transferred to their infants.

Aim: The aim of the study was to evaluate the effect of high-dose probiotic supplementation to women during late pregnancy and lactation on cytokine profile and secretory IgA (sIgA) in breast milk and thus to study if differences in breast milk composition can affect lactoferrin and sIgA levels in stool samples of newborns. The safety of maternal probiotic administration on neonatal growth pattern and gastrointestinal symptoms were also evaluated.

Methods: In a double-blind, placebo-controlled, randomized trial, 66 women took either the probiotic (n = 33) or a placebo (n = 33) daily. Levels of interleukins (IL-6, IL-10 and IL-1β), transforming growth factor-β1 (TGF-β1), and sIgA in breast milk; and the level of sIgA and lactoferrin in newborn stool samples were analyzed at birth and then again at one month of life. Antropometrical evaluation and analysis of gastrointestinal events in newborns was also performed.

Results: Probiotic maternal consumption had a significant impact on IL6 mean values in colostrum and on IL10 and TGF-β1 mean values in mature breast milk. Fecal sIgA mean values were higher in newborns whose mothers took the probiotic product than in the control group. Probiotic maternal supplementation seems to decrease incidence of infantile colic and regurgitation in infants.

Conclusion: High-dose multi-strain probiotic administration to women during pregnancy influences breast milk cytokines pattern and sIgA production in newborns, and seems to improve gastrointestinal functional symptoms in infants.

Keywords: functional GI diseases; immunology; pediatric gastroenterology; probiotics/prebiotics.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Breast milk cytokine patterns in treatment (T) and control (C) newborns at observational times T0 and T30. (A) (Interleukin-1β mean values); (B) (Inteleukin-10 mean values); (C) (Interleukin-6 mean values); (D) (Transforming Growth Factor mean values).
Figure 3
Figure 3
Secretory IgA (sIgA) in breast milk and stools, in treatment (T) and control (C) groups at observational times T0 and T30. (A) (Secretory IgA (sIgA) mean values in breast milk); (B) (Secretory IgA (sIgA) mean values in stools).
Figure 4
Figure 4
Fecal lactoferrin in treatment (T) and control (C) groups at observational times T0 and T30.
Figure 5
Figure 5
Growth pattern in treatment (T) and control (C) groups.
Figure 6
Figure 6
Functional gastrointestinal disorders (FGIDs) in treatment (T) and control (C) groups.

References

    1. Rautava S., Luoto R., Salminen S., Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat. Rev. Gastroenterol. Hepatol. 2012;9:565–576. doi: 10.1038/nrgastro.2012.144.
    1. Crosby M.S., Blattner C.M., Goedken M., Murase J.E. Update: Do probiotics prevent or treat pediatric atopic dermatitis? Pediatr. Allergy Immunol. 2016;27:425–428.
    1. Vitali B., Cruciani F., Baldassarre M.E., Capursi T., Spisni E., Valerii M.C., Candela M., Turroni S., Brigidi P. Dietary supplementation with probiotics during late pregnancy: Outcome on vaginal microbiota and cytokine secretion. BMC Microbiol. 2012;12:236. doi: 10.1186/1471-2180-12-236.
    1. Di Mauro A., Neu J., Riezzo G., Raimondi F., Martinelli D., Francavilla R., Indrio F. Gastrointestinal function development and microbiota. Ital. J. Pediatr. 2013;39:15. doi: 10.1186/1824-7288-39-15.
    1. Mastromarino P., Capobianco D., Miccheli A., Praticò G., Campagna G., Laforgia N., Capursi T., Baldassarre M.E. Administration of a multistrain probiotic product (VSL#3) to women in the perinatal period differentially affects breast milk beneficial microbiota in relation to mode of delivery. Pharmacol. Res. 2015;95–96:63–70.
    1. Schreck Bird A., Gregory P.J., Jalloh M.A., Risoldi Cochrane Z., Hein D.J. Probiotics for the Treatment of Infantile Colic: A Systematic Review. J. Pharm. Pract. 2016 doi: 10.1177/0897190016634516.
    1. Indrio F., Di Mauro A., Riezzo G., Civardi E., Intini C., Corvaglia L., Ballardini E., Bisceglia M., Cinquetti M., Brazzoduro E., et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: A randomized clinical trial. JAMA Pediatr. 2014;168:228–233. doi: 10.1001/jamapediatrics.2013.4367.
    1. Guandalini S., Magazzù G., Chiaro A., La Balestra V., Di Nardo G., Gopalan S., Sibal A., Romano C., Canani R.B., Lionetti P., et al. VSL#3 improves symptoms in children with irritable bowel syndrome: A multicenter, randomized, placebo-controlled, double-blind, crossover study. J. Pediatr. Gastroenterol. Nutr. 2010;51:24–30.
    1. Distrutti E., Cipriani S., Mencarelli A., Renga B., Fiorucci S. Probiotics VSL#3 protect against development of visceral pain in murine model of irritable bowel syndrome. PLoS ONE. 2013;8:e63893.
    1. Jaffe A.C. Failure to thrive: Current clinical concepts. Pediatr. Rev. 2011;32:100–107. doi: 10.1542/pir.32-3-100.
    1. Savino F., Pelle E., Palumeri E., Oggero R., Miniero R. Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: A prospective randomized study. Pediatrics. 2007;119:e124–e130. doi: 10.1542/peds.2006-1222.
    1. Lane M.M., Czyzewski D.I., Chumpitazi B.P., Shulman R.J. Reliability and validity of a modified Bristol Stool Form Scale for children. J. Pediatr. 2011;159:437–441.e1. doi: 10.1016/j.jpeds.2011.03.002.
    1. Hyman P.E., Milla P.J., Benninga M.A., Davidson G.P., Fleisher D.F., Taminiau J. Childhood functional gastrointestinal disorders: Neonate/toddler. Gastroenterology. 2006;130:1519–1526. doi: 10.1053/j.gastro.2005.11.065.
    1. Rautava S., Kalliomäki M., Isolauri E. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. J. Allergy Clin. Immunol. 2002;109:119–121. doi: 10.1067/mai.2002.120273.
    1. Kalliomaki M., Ouwehand A., Arvilommi H., Kero P., Isolauri E. Transforming growth factor-beta in breast milk: A potential regulator of atopic disease at an early age. J. Allergy Clin. Immunol. 1999;104:1251–1257. doi: 10.1016/S0091-6749(99)70021-7.
    1. Ogawa J., Sasahara A., Yoshida T., Sira M.M., Futatani T., Kanegane H., Miyawaki T. Role of transforming growth factor-β in breast milk for initiation of IgA production in newborn infants. Early Hum. Dev. 2004;77:67–75. doi: 10.1016/j.earlhumdev.2004.01.005.
    1. Corthésy B. Role of secretory IgA in infection and maintenance of homeostasis. Autoimmun. Rev. 2013;12:661–665. doi: 10.1016/j.autrev.2012.10.012.
    1. Cleveland M.G., Bakos M.A., Pyron D.L., Rajaraman S., Goldblum R.M. Characterization of secretory component in amniotic fluid. Identification of new forms of secretory IgA. J. Immunol. 1991;147:181–188.
    1. Akiho H., Khan W.I., Al-Kaabi A., Blennerhassett P., Deng Y., Collins S.M. Cytokine modulation of muscarinic receptors in the murine intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 2007;293:G250–G255. doi: 10.1152/ajpgi.00545.2006.
    1. Kole A., Maloy K.J. Control of intestinal inflammation by interleukin-10. Curr. Top. Microbiol. Immunol. 2014;380:19–38.
    1. Fields D.A., Demerath E.W. Relationship of insulin, glucose, leptin, IL-6 and TNF-α in human breast milk with infant growth and body composition. Pediatr. Obes. 2012;7:304–312. doi: 10.1111/j.2047-6310.2012.00059.x.
    1. Mastromarino P., Capobianco D., Campagna G., Laforgia N., Drimaco P., Dileone A., Baldassarre M.E. Correlation between lactoferrin and beneficial microbiota in breast milk and infant’s feces. Biometals. 2014;27:1077–1086. doi: 10.1007/s10534-014-9762-3.
    1. Buonavolontà R., Coccorullo P., Turco R., Boccia G., Greco L., Staiano A. Familial aggregation in children affected by functional gastrointestinal disorders. J. Pediatr. Gastroenterol. Nutr. 2010;50:500–505. doi: 10.1097/MPG.0b013e3181b182ef.

Source: PubMed

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