1. The Prevention of Celiac Disease in Predisposed Infants
Ashley Kindervater
Dept. of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg VA
HNFE 4004, Spring, 2016
2. Abstract:
Celiac disease is an autoimmune disease that damages the lining of the small
intestine when gluten is in ingested. People with first-degree relatives who suffer from
celiac disease have a 1 in 22 chance of also developing celiac disease, making
prevention research a high priority (University of Chicago, 2015). Looking at various
prevention methods, I sought to find out if celiac disease can be prevented in
predisposed infants. Research regarding breastfeeding and time of gluten introduction
proved to not be a supported prevention method. By introducing gluten earlier, the
development of the disease was delayed but in the end made no difference. Another
method of prevention was mode of delivery at birth. It was found that vaginal delivery is
much more supported in helping with the gut microbiome of infants which could result in
some type of defense against the immune response of those with CD. Finally, it was
found that supplementation of probiotics does provide as a defense mechanism but
further research must be conducted as to which strains should be supplemented.
Probiotic supplementation does not cure celiac disease but rather helps treat it as long
as supplements are being taken regularly. Overall, probiotic supplementation and
vaginal delivery are the strongest known prevention methods to date and with further
research more may be known on how parents can prevent the inheritance of this
disease to their children.
3. Introduction:
The question I was posing was “Can celiac disease be prevented in predisposed
infants?” About 1 in 133 healthy people suffer from celiac disease in the United States
(University of Chicago, 2005). Celiac disease is an autoimmune disease that affects the
villi of the small intestine when gluten is ingested. In a healthy person the villi of the
small intestine stand up like small fingerlike projections and aid in the absorption of
nutrients. In a person with celiac disease, the villi are flattened and cannot properly
absorb nutrients. As of now there is no cure for this disease besides sticking to a strictly
gluten-free diet for life. If untreated, celiac disease can lead to iron deficiency anemia,
osteoporosis, infertility, lactose intolerance, vitamin and mineral deficiencies, central
and peripheral nervous system disorders, pancreatic insufficiency, intestinal lymphomas
and other gastrointestinal cancers, etc. With all of the risks that celiac disease
predisposes people to, it is very important to research prevention methods for
predisposed infants.
Literature Review:
There are several common practices that attempt to prevent celiac disease in
infants. The three methods for prevention of celiac disease that I looked at were breast
feeding and time of gluten introduction, mode of delivery and supplementation of
probiotics.
4. Breastfeeding is often considered a preventative measure in the development of
CD due to its abundance of passive immunity factors like lysozyme, lactoferrin, and IgA
antibodies. Also, breast feeding has been proven to prevent several GI infections,
decrease gut permeability, and contain small amounts of allergens, like gluten, which
can aid in the development of tolerances (Chmielewska et al., 2015). While all of these
things may be true of breast feeding, I sought to research how effective these things
were in actually preventing celiac disease. In one study, two trials were conducted
where times of gluten introduction during breastfeeding were compared. The presence
of celiac disease at 5 years of age was observed. One trial compared the development
of CD in patients introduced to gluten between 4-6 months of age while being breastfed
versus a control group and another trial compared the presence of CD in children
introduced to gluten at 6 months compared to 12 months. It was found that all subjects
eventually developed celiac disease, but some sooner than others. Results showed that
infants who were introduced to gluten at 6 months of age while being breastfed versus
12 months of age while being breastfed, did not develop celiac disease by the age of 2,
however by 5 years of age, all subjects had the disease (Chmielewska et al., 2015).
These same results were also concluded in a study done by the North American Society
for the Study of Celiac Disease, where they found that breastfeeding did not aid in
prevention of celiac disease (Lebwohl et al., 2015). Another study, by Radlovic et al.
(2010), retrospectively looked at the medical records of 89 infants who were diagnosed
with CD and divided them into two groups: one that consisted of infants who were
exclusively breasted at the time of gluten introduction and another group that had not
been breastfed. It was found that breastfeeding did put off the development of CD a little
5. bit longer than those who had not been breastfed. The severity of the disease was not
affected by either variable. Conversely, a study that was done in Sweden by Shamir et
al. (2014) proved otherwise. In the 1930s there was a Swedish epidemic of symptomatic
celiac disease. This was due to a change in dietary recommendations that said to delay
the introduction of all gluten-containing foods to infants until 6 months of age. Later on
the prevalence of CD was decreased once the recommendation of gluten introduction
was changed to >4 months of age. It was also suggested that the amount of gluten
introduced to children plays a role in the development of CD. Lastly, this study found
that children that were breastfed while being introduced to gluten had a 52% risk
reduction of development of the disease compared to those who were not breastfed.
Another factor that has been studied in the prevention of celiac disease in infants
is the mode of delivery. Because the vagina is known to have an abundant source of
micro flora, there has been a connection found to the gut microbiota of vaginally
delivered versus cesarean delivered infants. The GI tracts of neonates are colonized
immediately after birth from the mother and have a strong correlation to the
development of the infant’s immune system and the development of autoimmune
diseases. A study preformed by Biasucci et al. (2008) measured the microbiota in fecal
samples of infants who were vaginally delivered versus cesarean section delivery. It
was found that there was a substantial absence of Bifidobacteria, which is an inhabitant
of the GI tract. This finding concluded that only vaginal delivery promotes the production
of the cytokines needed for neonatal immunity, thus there is a strong link between
cesarean delivery and disturbed intestinal colonization of bacteria. The gut microbiota in
patients with celiac disease is much less diverse than healthy individuals, making this
6. an important factor when looking at the prevention of the disease. Since 1996, the rate
of cesarean delivery in the United States has increased by 48% and with this increase,
the prevalence of autoimmune diseases like type 1 diabetes, Crohn’s disease and
celiac disease has also risen. No association between Crohn’s disease and cesarean
delivery has been proven, but children born via cesarean delivery are significantly more
likely to suffer from celiac disease and be hospitalized for gastroenteritis (Neu et al.
2011). In a retrospective study preformed by the American Academy of Pediatrics,
1,950 children were observed and information on intestinal disease manifestation, mode
of delivery and gestational age at birth, postnatal complications, and breastfeeding was
collected. It was found that there is a significant correlation between patients who were
delivered via cesarean section and patients who developed celiac disease in
comparison to control subjects (Biasucci et al. 2008). Although it is not always up to the
mother how her baby will be delivered due to various complications, by opting to deliver
vaginally if possible, infants would have a more diverse gut microbiota which can aid in
the prevention of celiac disease.
In relation to mode of delivery, another prevention method of celiac disease that
was studied was the supplementation of probiotics like Bifidobacterium to children who
are predisposed to this disease. Patients with celiac disease have a reduction in
beneficial species of bacteria and an increase in potentially pathogenic species in
comparison to healthy subjects (Marasco et al., 2015). In a study published by the
journal of Digestive Diseases and Sciences, there were 3 groups of children. The first
were children with celiac disease given the B. breve strains for 3 months while on a
gluten free diet, the second group of children with CD were given a placebo while on a
7. gluten free diet, and the third group of healthy children was given no treatment and
served as the control group. It was observed at the end of the three month trial that the
children with CD who were given the probiotic had lower levels of pro-inflamatory
cytokine tumor necrosis factor alpha (TNF-), however after the intervention was over
the levels returned back to normal (Klemenak et al., 2015). Fernando et al. (2014) found
that lactobacilli and bifidobacteria are reduced in the gut of CD patients and that these
bacteria are promising targets for probiotic therapy. There are strains of these bacteria
that can produce enzymes that break down gliadin peptides and induce anti-
inflammatory effects which could potentially treat this disorder (Moraes et al. 2014).
Currently there needs to be more research to determine the role of gut microbiota in the
pathogenesis of celiac disease and the impact of the therapeutic use of probiotics, for
this could be a strong lead into the potential treatment of this disease.
Conclusions:
In light of the question “how can celiac be prevented in predisposed infants,”
some conclusions can be drawn. The popular conclusion from breastfeeding and gluten
introduction research shows that breastfeeding and earlier introduction of gluten is not a
strong prevention method, but can delay the onset for a little while. These studies were
only conducted with predisposed infants, so it is important to note that it may be
beneficial for infants who are not predisposed to the development of CD to be
exclusively breastfed for at least 6 months due to the gliadin that is found in breast milk
which can contribute to several immune factors (Brandtzaeg 2002 and Hanson et al.
2000). It is encouraged that all infants should be exclusively breastfed for at least 6
8. months regardless of various disease predispositions because of the lysozyme,
cytokines, and lactoferrin found in breast milk that are directly correlated with the
effectiveness of the infants’ immune systems.
When it comes to mode of infant delivery, vaginal delivery is by far the most
beneficial in the prevention of CD in predisposed infants. All research concluded that
infants delivered vaginally had a significant increase of gut microbiota and those
delivered cesarean lacked strains of Bifidobacterium which is crucial in the protection of
intestinal damage. Further research should be conducted to find out if the vaginal
microflora of mothers can somehow be given to infants who had to have a cesarean
delivery.
The supplementation of probiotics looks to be the most promising of prevention
methods for celiac disease. Bifidobacteria and Lactobacilli both have strains which
produce enzymes that can break down gliadin. Further research needs to be conducted
on specifically which of these strains and which combination of strains would be the
most beneficial to supplement to patients with CD.
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