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sequently produced could stimulate intestinal peristalsis and increase fecal moisture
with osmotic pressure. 71
4.5.3 Immune Modulation
The intestinal epithelial cells, as part of the gut-associated lymphoid tissue
(GALT), play a crucial role in signaling and mediating innate immune responses.
Epithelial cells also produce essential signals for the induction of memory pathways
of the adaptive immune system. The adaptive immune system exists of B cells, pro-
ducing antibodies against proteins (humoral immunity) and T cells removing anti-
gens and viral infected cells (cellular immunity). These immune responses develop
in specialized lymphoid structures, predominantly found in the ileum of the small
intestine, the Peyer's patches (PP).
The GALT receives signals from the microbiota or food antigens and induces a
state of nonresponsiveness, so-called mucosal tolerance. 72 When pathogenic bacteria
invade the intestinal mucosa, however, it should elicit strong humoral and cellular
immune responses. The composition and/or the activity of the microbiota influence
the maturation and modulation of the immune system activity. 73 This is clearly illus-
trated in germ-free animals that are shown to have an immature and poorly devel-
oped immune system. 74 The absence of a normal microbiota can also result in an
increased antigen transport across the gut mucosa. 75 The communication between
GALT and the microbiota is based on rapid recognition of specific bacterial products
through pattern recognition receptors (PRR) like the membrane-associated TLRs.
These receptors are essential for discriminating potential pathogens from the ben-
eficial members of the gut microbiota and, thus, for immune homeostasis both in the
gut and systemically. 72
4.5.3.1 Immune Activity
HMOs have been shown to influence the immune system not only through the
intestinal flora, but also by direct interaction with immune cells. 76 With its effect on
the microbiota, GOS indirectly influence mucosal and systemic immune activity. 77
In addition, the increased production of SCFAs by GOS fermentation contributes
to the maintenance of a noninflammatory environment in the intestine as several of
these SCFAs have been shown to modulate immune responses. 78-81 Butyrate has also
been shown to inhibit NF-κβ activation in intestinal epithelial cells under proinflam-
matory conditions 78,79 and has also been shown to inhibit T-cell activation. 80 Similar
findings have also been reported for acetate and propionate. 81
The GOS/lcFOS mixture also has a (partially) microbiota-independent effect
on the immune response. 82 It increased the proportion of fecal bifidobacteria and
lactobacilli and enhanced, vaccine-specific, delayed-type hypersensitivity (DTH)
responses dose dependently. FOS/inulin induced similar effects on the gut microbi-
ota. However, FOS/inulin scFOS/1cFOS did not enhance DTH responses, indicating
that an increase in the proportions of bifidobacteria and lactobacilli is not sufficient
for the observed immunomodulatory effect.
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