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Human milk composition differs in healthy mothers and mothers with celiac disease

Abstract

Purpose

To investigate whether breast-milk composition and microbiota differ in healthy mothers and mothers with celiac disease (CD) to ultimately contribute to identify additional factors determining CD risk.

Methods

Breast-milk samples from healthy mothers (n = 12) and mothers with CD (n = 12) were collected. Cytokines and secretory immunoglobulin A (sIgA) were analyzed by bead-arrays and flow cytometry and human milk oligosaccharides (HMOs) were assessed by capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection. Breast-milk microbiota composition was analyzed by conventional and quantitative real-time PCR.

Result

Breast milk from CD mothers showed significantly lower levels of interleukin (IL) 12p70 (P < 0.042), transforming growth factor (TGF)-β1 (P < 0.018) and sIgA (P < 0.003) and almost significantly lower levels of interferon (IFN)-γ (P < 0.058). Six mothers in each group belonged to the secretor Le(a−b+) type, one to the secretor Le(a−b−) type and five to the non-secretor Le(a+b−) type. CD mothers of non-secretor Le(a+b−) type showed increased Lacto-N-tetraose content (P < 0.042) compared with healthy mothers. CD mothers’ milk showed reduced gene copy numbers of Bifidobacterium spp. (P < 0.026) and B. fragilis group (P < 0.044).

Conclusion

CD mothers’ breast milk is characterized by a reduced abundance of immunoprotective compounds (TGF-β1 and sIgA) and bifidobacteria. The reduction in these components could theoretically diminish the protective effects of breast-feeding on the child’s future risk of developing CD.

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Fig. 1

Abbreviations

ACN:

Acetonitrile

APTS:

9-Aminopyrene-1,4,6-trisulfonate

CD:

Celiac disease

Ct:

Cycle threshold

DGGE:

Denaturing gradient gel electrophoresis

DFL:

Difucosyllactose

DF LNH:

Difucosyllacto-N-hexaose

CE-LIF:

Electrophoresis-laser-induced fluorescence

ESPGHAN:

European Society of Pedriatric Gastroenterology Hepatology and Nutrition

Fuc:

Fucose

F LNH:

Fucosyllacto-N-hexaose

FL:

Fucosyllactose

FUT:

Fucosyltransferase

Gal:

Galactose

Glu:

Glucose

GFD:

Gluten free diet

TGF:

Transforming growth factor

HLA:

Human leukocyte antigen

HMO:

Human milk oligosaccharide

IFN:

Interferon

IL:

Interleukin

N-Acetyl:

N-Acetylglucosamine

LNT:

Lacto-N-tetraose

LIF:

Laser-induced fluorescence

LNFP:

Lacto-N-fucopentose

LNDFH:

Lacto-N-difucosylhexaose

Le:

Lewis

Se:

Secretor

sIgA:

Secretory immunoglobulin A

Neu5Ac:

Sialic acid

SL:

Sialyllactose

TNF:

Tumor necrosis factor

TFA:

Trifluoroacetic acid

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Acknowledgments

This work was supported by Grants AGL2011-25169 and Consolider Fun-C-Food CSD2007-00063 from the Spanish Ministry of Economy and Competitiveness (MINECO). The scholarship to M. Olivares from Consejo Superior de Investigaciones Científicas (CSIC) is fully acknowledged.

Conflict of interest

The authors declare that they do not have conflict of interest.

Ethical standards

This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the Committee on Ethical Practice at the Hospital Universitari Sant Joan (Tarragona, Spain). All the mothers participating in the study gave written informed consent.

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Correspondence to Yolanda Sanz.

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Olivares, M., Albrecht, S., De Palma, G. et al. Human milk composition differs in healthy mothers and mothers with celiac disease. Eur J Nutr 54, 119–128 (2015). https://doi.org/10.1007/s00394-014-0692-1

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Keywords

  • Celiac disease
  • Human milk
  • Immunity
  • Microbiota