Celiac Disease Influences Breast Milk Composition

  • Celiac disease is an autoimmune condition where the body’s immune system reacts to dietary gluten by damaging the lining of the small intestine.
  • Milk from mothers with celiac disease has lower concentrations of protective immune factors, including secretory IgA and probiotic bacteria, compared with healthy controls.
  • Although breastfeeding may reduce the risk of subsequent celiac disease development, milk from mothers with celiac disease may not provide sufficient quantities of these protective factors.
  • More longitudinal studies are needed to fully understand how variation in breast milk immune components and probiotic concentration influences the development of celiac disease and other autoimmune conditions later in life.

 

Nearly 1% of Americans suffer from the autoimmune disorder called celiac disease. For these people, the digestion of foods containing gluten (a protein found in wheat, barley and rye) causes the immune system to attack the lining of their small intestine, resulting in inflammation that prevents absorption of nutrients. The intestinal damage from celiac disease can lead to anemia, osteoporosis and weight loss. But can it also influence breast milk composition? A new study reports for the first time that mothers with celiac disease produce milk with lower concentrations of protective factors, including antibodies and probiotic bacteria (1).

Guts, Immunity and Milk

If celiac disease affeHappy Mother Breast Feeding Her Baby Infantcts the small intestine, why would it affect breast milk composition? Although milk is produced by the mammary gland, some milk components may have their origins in the maternal gut. In fact, in a lactating female, the mammary gland develops a special relationship with the lymphatic (immune) system in the gut (called GALT, for gut associated lymphoid tissue); take, for example, secretory immunoglobulin A (sIgA), the predominant antibody in human milk. Milk sIgA molecules are derived from maternal IgA antibodies directed against pathogens that the mother encountered in her own digestive tract. Damage to the villi that line the small intestine in mothers with celiac disease could influence maternal IgA production and, subsequently, the sIgA concentration in breast milk.

Another important consideration is the intimate connection between the maternal immune system and milk immune components. Celiac disease, like other autoimmune conditions, is associated with an inflammatory immune response. As a result, the concentration of immune factors associated with inflammation, such as the cell signaling proteins interleukin 12 (IL-12) and transforming growth factor-beta 1 (TGF-ß1), may be altered in maternal serum and in breast milk.

Taking these factors into account, Olivares et al (1) collected breast milk samples from mothers with celiac disease and healthy controls to compare the concentrations of sIgA, cytokines involved with the inflammatory response (including IL-12 and TGF-ß1), as well as DNA from probiotic bacteria.

An important component of the investigators’ study design is their inclusion criteria for the celiac disease group. They only collected milk from celiac disease mothers that had consumed a gluten-free diet for at least two years and had no reported symptoms of the disease at the time of the study. By doing so, they were able to rule out the possible effects of an active inflammatory response in the maternal gut tissue (or even malnourishment) as a cause for the differences they detected in milk composition between the celiac disease and control groups.

Keeping in mind the small sample size (24 mothers total, 12 in each group), Olivares et al (1) made some exciting observations. First, milk from mothers with celiac disease was significantly lower in the concentrations of sIgA, IL-12 and TGF-ß1. Moreover, their milk had less DNA from gut-derived probiotic bacteria, including Bifidobacterium species and Bacteroides fragilis, although these differences were not as pronounced as those for sIgA and cytokines.

Lower levels of Bifidobacterium species in the gut also were reported in milk from mothers with allergies (2), suggesting a relationship between the maternal immune system’s response to “false alarms” and milk probiotic bacteria. On the other hand, higher concentrations of milk sIgA were associated with maternal infection, psychological stress, and heightened microbial exposure (3, 4). Olivares et al’s (1) finding of reduced concentrations of sIgA in celiac mothers suggests that autoimmunity, previous inflammation in the maternal gut, or a combination of both factors may have suppressed maternal IgA (and cytokine) production. This issue could have been more fully addressed had the investigators measured sIgA or cytokine levels in serum from the mothers to compare with levels in their milk. For example, although the mothers with celiac disease reported no active symptoms, they may still have had a pro-inflammatory immune profile compared with the control group.

Breastfeeding and Celiac Disease: It’s Complicated

Olivares et al (1) provide the first evidence that celiac disease influences human milk composition. That alone is a significant contribution to the study of human lactation. But their study may make its largest impact by contributing to the debate over whether or not breastfeeding provides a protective effect against the development of celiac disease. Despite numerous studies identifying a reduced risk of developing celiac disease associated with breastfeeding (5–7), others (8) failed to identify any protective effects.

At the heart of the debate is whether breastfeeding at the time of gluten introduction to the infant’s diet delays the onset of celiac disease, or even prevents the development of the disease in infants with a genetic predisposition. Olivares et al (1) believe that their findings can help provide much needed resolution. Each of the milk factors they found to be significantly lower in celiac disease mothers has been implicated as potential protective components against the development of celiac disease, other autoimmune diseases (e.g. Crohn’s disease) and allergies. TGF-ß1 is believed to help regulate the infant’s immune response to food antigens (9), sIgA is critical in regulating the mucosal immunity in the infant’s gut (10) and imbalances in probiotic bacteria are connected to the development of autoimmune diseases (1, 11). Taken together, these components are intimately involved in the development of the infant’s immune response to environmental antigens such as gluten.

The majority of studies investigating the relationship between breastfeeding and celiac disease are retrospective in design; study participants are asked to recall information about the duration of breastfeeding and age at which gluten was first introduced into the diet. As a result, breast milk composition has never been considered as a possible confounding variable.

At this point, we know too little about the consequences of variation in milk immune components on infant outcomes to say definitively that milk composition could be a confounding variable in the development of celiac disease. For example, although mothers with celiac disease produce lower concentrations of sIgA and TGF-ß1 than mothers without the disease, how do we know whether these levels are insufficient to promote oral tolerance of food antigens?

Despite these gaps in our knowledge, the results of Olivares et al’s (1) study illustrate just how important it is for future studies on the relationship between breastfeeding and celiac disease to incorporate data on breast milk composition. This type of data necessitates a longitudinal rather than retrospective study design, simply because people do not know the composition of the milk they were fed as an infant. The protective components in breast milk not only influence infant immune function at the time they are ingested, they also are integral to the development of the infant’s immune system.

What’s a Mother to Do?

Regardless of whether the lower than normal levels of sIgA and TGF-ß1 in breast milk from mothers with celiac disease are sufficient to promote oral tolerance of gluten, these levels are still higher than those in infant formula. Moreover, the mean concentration of sIgA in milk from mothers with celiac disease, as reported by Olivares et al (1), actually is well within the ranges reported from other populations at the same stage of lactation (4, 12, 13), and mean concentrations of TGF-ß1 are higher than values reported by Tomicić et al (4).  Although their concentrations are lower than those from the healthy controls, milk protective factors from celiac disease mothers may still offer numerous benefits to their offspring. As we wait for more research, mothers with celiac disease should continue to breastfeed their infants, and preferably to continue breastfeeding during the time of gluten introduction to the infant’s diet. Low levels of protective factors are better than none at all.

1. Olivares M, Albrecht S, De Palma G, Ferrer MD, Castillejo G, Schols HA, et al (2014). Human milk composition differs in healthy mothers and mothers with celiac disease. Eur J Nutr [Apr 4 Epub ahead of print] PubMed PMID: 24700375.

2. Grönlund MM, Gueimonde M, Laitinen K, Kociubinski G, Grönroos T, Salminen S, et al (2007). Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease. Clin Exp Allergy 37: 1764-1772.

3. Groer M, Davis M, Steele K (2004). Associations between human milk SIgA and maternal immune, infectious, endocrine, and stress variables. J Hum Lact 20: 153-158; quiz 159-163.

4. Tomicić S, Johansson G, Voor T, Björkstén B, Böttcher MF, Jenmalm MC (2010). Breast milk cytokine and IgA composition differ in Estonian and Swedish mothers-relationship to microbial pressure and infant allergy. Pediatr Res 68: 330-334.

5. Akobeng AK, Ramanan AV, Buchan I, Heller RF (2006). Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child 91: 39-43.

6. Ivarsson A, Hernell O, Stenlund H, Persson LA (2002). Breast-feeding protects against celiac disease. Am J Clin Nutr 75: 914-921.

7. Ivarsson A, Myléus A, Norström F, van der Pals M, Rosén A, Högberg L, et al (2013). Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics 131: e687-e694.

8. Størdal K, White RA, Eggesbø M (2013). Early feeding and risk of celiac disease in a prospective birth cohort. Pediatrics 132: e1202-e1209.

9. Penttila IA (2010). Milk-derived transforming growth factor-beta and the infant immune response. J Pediatr 156(2 Suppl): S21-S25.

10. Rogier EW, Frantz AL, Bruno ME, Wedlund L, Cohen DA, Stromberg AJ, et al (2014). Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc Natl Acad Sci U S A 111: 3074-3079.

11. Rinne M, Kalliomaki M, Arvilommi H, Salminen S, Isolauri E (2005). Effect of probiotics and breastfeeding on the Bifidobacterium and Lactobacillus/Enterococcus microbiota and humoral immune responses. J Pediatr 147: 186-191.

12. Cruz JR, Carlsson B, García B, Gebre-Medhin M, Hofvander Y, Urrutia JJ, et al (1982). Studies on human milk III. Secretory IgA quantity and antibody levels against Escherichia coli in colostrum and milk from underprivileged and privileged mothers. Pediatr Res. 16(4 Pt 1): 272-276.

13. Prentice AM, Spaaij CJ, Goldberg GR, Poppitt SD, van Raaij JM, Totton M, et al (1996). Energy requirements of pregnant and lactating women. Eur J Clin Nutr 50(Suppl 1): S82-S110; discussion S10-S11.

 

Contributed by
Dr. Lauren Milligan Newmark
Research Associate
Smithsonian Institute