The effects of the different bread types of fully known composition on gastrointestinal symptoms in individuals with non-coeliac wheat sensitivity.

Although wheat and gluten containing food products are generally considered to
be healthy, a large number of individuals in the general population reduce or
limit their intake because of possible symptoms and/or replace wheat by other
grain, such as spelt. This non-coeliac gluten or wheat sensitivity (NCGS/NCWS)
which is accompanied by a range of (extra-)intestinal complaints soon after
consuming wheat or gluten, which improve after gluten/wheat withdrawal.
Evidence for a biological rationale is however limited, nor for the exact
contributing compound. The term NCGS implies that gluten is the trigger for the
reported symptoms. However, besides gluten, wheat, spelt, barley, rye and their
derivatives contain other components which may contribute to symptoms,
including fermentable carbohydrates and amylase trypsin inhibitors (ATIs).
Therefore, the term NCWS is preferred. The biochemical composition differs
between grains and specific processing methods in bread, and may impact
gastrointestinal tolerability in NCWS.

In this respect, it is unclear what the impact of grain type, bread processing
and the resulting compositional changes in the bread to be consumed is. Thus
far studies did neither directly compare the effects of different wheat types,
nor the effects of their specific processing in bread making on GI symptoms in
individuals with NCWS. Ancient wheat species (e.g. Emmer) have been suggested
to have health benefits when compared with modern cultivars of bread (e.g.
bread wheat and spelt). Moreover, it appears that processing methods in bread
making can also influence the biochemical composition of bread, resulting in
decreased amounts of (bioactive) proteins and amounts of FODMAPs in bread
(28-31) which could theoretically result in improved gastrointestinal (GI)
tolerability of wheat products in NCWS. Previous studies suggest the intestinal
microbiota may be a relevant factor in symptom generation.

We feel that studies addressing the effects of wheat-based foods, *as consumed
part of a typical daily human diet*, are needed to obtain reliable data that
are useful for optimizing appropriate food processing and product development
as well as for dietary recommendations to consumers. Therefore, we aim to
perform a three-arm randomized (cross-over) study to assess the effects of
consuming bread made from hexaploid Bread Wheat and Spelt wheat, and/or
tetraploid Emmer wheat each prepared as yeast-fermented and sourdough fermented
on symptoms in individuals with NCWS. Additionally, we aim to explore the
potential role of the microbiome in symptom generation in an in vitro
fermentation study.

The primary objective of this study is to investigate the effects of breads
made from well-characterised Bread wheat, Emmer wheat, or Spelt wheat of fully
known composition each yeast (study A) or sourdough (study B) fermented on
intestinal symptoms in individuals with NCWS. Further, this study has secondary
objectives: first to investigate te effects of the different breads on
individual GI and extra-intestinal symptoms in individuals with NCWS. Further
to compare the effects yeast or sourdough-fermented within each type of bread
(Bread wheat, Spelt wheat, Emmer wheat) on (extra)intestinal symptoms in
individuals with NCWS. Additionally, we want to investigate the effects of
these breads on the composition and activity of the gut microbiota in vitro.

The two studies comprise a randomized (cross-over) design.

Participants will be recruited into one of two studies. As part of each study,
participants will undergo three intervention days (separated by a wash-out
period) in a cross-over design, according to the randomisation scheme:
* Study A: randomised order of yeast-fermented bread made of Bread Wheat, Emmer
or Spelt.
* Study B: randomised order of sourdough fermented bread made of Bread Wheat,
Emmer or Spelt.
Study A will be completed first, thereafter Study B will be completed.

Participants may experience some small burden during this study. After the
initial screening visit, required to determine eligibility of participants to
the study, participants will have to visit the Maastricht University Medical
Center + (MUMC+)/Wageningen University (WUR) two times. In total, a participant
will to spend approximately 1,5 hours at MUMC+/WUR facility. They will have to
consume in total 5 slices of study bread for breakfast and lunch during three
separate test days. The study breads are considered to be a harmless food
product, consumed on a daily basis by the general population worldwide. The
participants may or may not experience (mild) gastrointestinal symptoms after
the consumption of the study bread, since the included participants suffer from
self-reported wheat sensitivity. Such symptoms typically improve or disappear
shortly (mostly within hours) after gluten is withdrawn from the diet. In a
subgroup of participants (i.e. those who have not previously been tested for
coeliac disease, and who still consume a low level of gluten in their diet) a
blood sample will be taken (by venepuncture) during an additional visit of +/-
20 min prior to the screening visit to exclude coeliac disease by means of
serological tests on anti-tTG IgA. Faecal sample collection is without any
risks. Moreover, questionnaires will have to be filled out at several occasions
during this study.

The study results will bring insights about the effects of the different types
of bread (grain type and processing type yeast fermented vs. sourdough
fermented). This information may help the participants to make well-informed
bread choices, with the goals to help minimise consumption related discomfort.