GALT and its functions. Non-fermentable fibres such as cellulose
seem to have fewer effects (4). These effects of inulins and
oligofructose/fructooligosacchrides (FOS) and other prebiotics are
described below. These serve as an example showing how the
immune system can be modulated by such dietary components.
INULIN AND PARAMETERS OF THE IMMUNE SYSTEM
Animal model studies
In a series of publications by Bruggencate et al. (5) it was shown that
oligofructose consumption in rats has a negative effect on the barrier
function of the intestine, as measured by the lowered resistance to
Salmonella translocation. With higher fermentation rates the effect
became more pronounced, and the effect could be abolished to a
large extent with dietary calcium.
Another effect on the innate immune system comes from the data by
Roller et al. (2004). They showed that inulin supplementation of rat
feed leads to increased production of interleukin (IL)-10 and
interferon-γfrom PP cells (6).
Model studies with chemically induced colitis in animals generally
show a beneficial effect of inulin consumption. E.g. Videla et al. (7)
found that with 10 percent inulin in the diet the inflammatory response
to dextran sulphate sodium was much less, and similar data were
The immune system is the host's defence both against attacks from
the outside, such as by viruses or bacteria and from the inside (e.g.
malignant cells). It consists of an innate part and the acquired or
adaptive part. The innate immune system is non-specific and
provides the early response to invasion and includes physical barriers
(e.g. mucous membranes), cell-mediated barriers for instance from
phagocytes and natural killer cells, and soluble factors such as
cytokines. The adaptive response of the immune system is specific
and occurs after the response by the innate part and involves the
activity of B- and T-lymphocytes. They modulate the function of other
immune cells or destroy cells infected with pathogens.
The immune activities in the gastrointestinal tract that protect the
intestine are located in a variety of tissues together called the gut-
associated lymphoid tissue (GALT). This system consists of the
following components (see Figure 1 and 2):
1. Peyer's patches (PP) found throughout the mucosa of the small
intestine. They are covered by special cells (M-cells), which can
take up (phagocytosis) soluble antigens and microorganisms and
release them into the PP. There these antigens are presented to T
and B lymphocytes.
2. Isolated lymphoid follicles are the functional equivalent of PP
present throughout the intestine, but especially in the colon and
3. Non-aggregated cells in the lamina propria consisting of T and B
cells, where the majority of the B cells secrete soluble IgA into the
gut lumen. This IgA is an important component of the
4. Intraepithelial lymphocytes are located in the interstitial spaces of
the mucosal epithelium, and they can be found in small and large
5. Mesenteric lymph nodes although not located in the intestine are
considered part of the GALT as they have strong interactions with
other parts of this system. The GALT is also the site where immune
system and components of the diet interact.
Dietary fibres defined shortly as nondigestible dietary carbohydrates
have various physiological effects that include a positive effect on
defecation, on serum lipids, on feelings of satiety (see for instance 3).
Insoluble fibres such as wheat bran are well known for their stool
bulking effect; in contrast, soluble fibres have less stool bulking
properties but exert their physiological effects after being fermented
by the resident colonic microbiota.
More and more evidence shows that fermentable fibres can affect the
vol 19 n 3 May/Jun 2008 Ag roFOOD industry hi-tech
Prebiotic dietary fibres and the
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ABSTRACT: This paper describes the effect of prebiotic fibres, especially of inulin and oligofructose, on the immune system. A brief
introduction of the immune system is followed by an overview of results from experimental animal trials on the relation of inulin
consumption and immune parameters. Then data from human volunteer studies in healthy and diseased people are presented,
followed by an overview of the data for inulin consumption and resistance to gastrointestinal infections. After a discussion about the
potential mechanisms that are based on the effects of inulin in the composition and activity of the colonic microbiota, it is concluded that
prebiotic fibres as inulin can affect the immune system in various ways. The results obtained so far underline the view that inulin may
support the immune system in a positive way which for instance may lead to increased resistance to infections, or less incidence of
atopic dermatitis. In people with colon diseases consumption of inulin (alone or in combination with probiotic bacteria) could lead to less
disease symptoms. It is also clear that more research will be required to fully substantiate these positive findings.
Figure 1. Schematic overview of the lymphoid elements of the gut-
associated lymphatic system. Peyer's patches (PP) and mesenteric
lymph nodes (MLN) are organised intestinal lymphoid follicles. (A-C)
Pathways of intestinal antigen uptake: luminal antigen can be taken up
by (A) intestinal epithelial cells, (B) interdigitating lamina propria
dendritic cells, and by (C) M cells. The lymphatic drainage of PP and
villus lamina propria goes to the MLN (direction of lymph flow indicated
by arrows). (Taken from 1)
Prebiotic consumption can have an effect on atopy and allergy as
shown in animal models. Fujitani et al. (19) suggested on the basis of
their mouse model studies with FOS from sucrose that these fructans
may have antiallergic activity.
Human studies in healthy volunteers
The effect of oligofructose consumption on barrier function as found
in rats (see above) could not be reproduced in humans even at high
consumption rates. In humans consuming oligofructose at 20 g/d (20)
or more (up to 30 g/d; 21) markers for barrier function were not
affected. These data show (again) the difficulties of translating data
from animal trials to a human situation.
Two studies with elderly people show that inulin consumption affects
their immune system. Guigoz et al. (22) noted that with the
consumption of 8 g/d of FOS from sucrose some inflammatory
response markers decreased. They showed in healthy elderly people
a decreased phagocytic activity of granulocytes and monocytes, as
well as a decreased expression of IL-6 mRNA in peripheral blood
monocytes after 3 weeks of FOS consumption. Bunout et al. (23)
investigated the effect of prebiotics on the response to vaccination in
elderly. A mixture of inulin and oligofructose (6 g/d) did not lead to a
changes immunological response on the volunteers with age > 70 y.
No changes in secretory IgA could be found, neither an effect on the
antibody titre after vaccination with influenza or pneumococcal
In another vaccination study with 8-months old infants that received 1
g of a 30/70 mixture of native inulin and oligofructose in 25 g cereal
for 10 weeks, Haschke et al. (24) showed that after vaccination with
measles vaccine IgG antibody titres were higher in the group
receiving the prebiotic mixture.
Roller et al. (25) investigated the effects of a synbiotic preparation on
the systemic immune system in colon cancer and polypectomised
patients. They concluded that there were only minor immune
reported by others (8) for the response to trintrobenzene sulphonate
in rats. In this latter model system it was shown that FOS
consumption reduced disease scores and lowered several
inflammatory markers and cytokines (9). In another mouse model
similar effects were found with an inulin/FOS mixture as well as an
upregulation of transforming growth factor-β(10). Another stimulatory
effect was reported in rats where FOS enhanced TNF-αand
prostaglandin E2 levels in serum after a lipopolysaccharide challenge
(11). These studies show that inulin/oligofructose can suppress
inflammatory symptoms by mechanisms that are microbiota related.
The work of Pierre and others in Min mice with fructo-
oligosaccharides in their feed shows that the GALT was modulated in
such a way that antitumoral activity was stimulated (12) and they
suggested that this might be due to the activation of an
immunosurveillance mechanism by inulin related to the suppression
of colon tumours (13). Other model studies with chemically induced
colon cancers showed similar data, but it remains to be elucidated
whether such effects are mediated through immune modulation as
suggested by Pierre et al. (12, 13).
γ-Inulin is a dahlia-derived inulin in a crystallised form with a high
molecular weight (14). This special type of inulin activates the
alternative complement pathway (part of the adaptive immune
response) and shows adjuvant activity when injected intraperitoneally
in mice (15). It was shown to enhance the function of murine antigen-
presenting cells and it enhanced production of complement factor C3
by macrophages (16).
Inulins with a different chain length exist which may have different
effects; it is well known that different ratios of fermentation products,
short chain fatty acids (SCFA) and lactate will arise from different
inulins (17). A recent report shows that this may also be the case for
the immune effects as in rats IgA production increases with
fermentation rate in the cecum, i.e. increases with decreasing chain
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Surprisingly, only the group that consumed 3.2 percent FOS in food
showed fewer episodes of diarrhoea; whilst with 4 percent no effect
was found. Looking at diarrhoeal episodes of less than 2 days, both
FOS percentages were effective. The effects became evident after 4
months of consumption. Juffrie et al. (39) used FOS from sucrose to
explore the effect in diarrhoeal diseases in children aged 1-14 years.
They could show that prebiotic consumption (2.5 - 5 g/d) shortened
the duration of diarrhoea, and that stools had a lower pH with FOS
consumption, indicative for increased fermentation and formation of
SCFA. Agustina et al. (40) reported comparable data for a synbiotic
preparation consisting of inulin, soy polysaccharides and L.
rhamnosus. Duration of diarrhoea was shortened in children suffering
from acute diarrhoea, but it remains difficult to decide whether this
was caused by the prebiotic, probiotic or both.
The extra consumption of iron and zinc also complicates drawing
unequivocal conclusions. Other investigators showed that
oligofructose consumption at 2 g/d led to less episodes with diarrhoea
or fever in children aged 7 - 19 months (41) with a concomitant trend
for an increased content of faecal bifidobacteria and a significant
decrease in potential pathogens, such as clostridia.
Arslanoglu et al. (42) showed similar data with a 9/1 GOS/FOS
mixture in children during the first 6 months of life. The prebiotic
mixture reduced the number of infectious periods and especially the
incidence of respiratory infections.
The immune alterations as described above can be brought about by
various mechanisms, as schematically shown in Figure 2.
The increase in bifidobacteria and lactobacilli due to prebiotic
consumption means that there is a change in the pattern of immune
effecting molecules from the lumen. More bifidobacterial cell wall
components, such as peptidoglycan or lipoteichoc acids, can have an
effect on the mucosal immune system (43). It has also been reported
that consumption of probiotic bifidobacteria leads to increased IgA
levels in small intestine and faeces (44) again indicating the effect of
these bacteria on the immune system. As pointed out before inulin
consumption leads to increased production of SCFA which may lead
to physiological effects of the mucosa, as it has been reported that
butyrate suppresses lymphocyte proliferation, reduces cytokine
expression and enhances IL-10 production in rats. Furthermore, as
modulating effects of the synbiotic that consisted of 10 g/d of
FOS/inulin and Bifidobacterium lactis and Lactobacillus rhamnosus in
the two patient groups. Other data for healthy humans are based on
the application of a 9:1 GOS/FOS mixture in infant foods. Moro et al.
(26) reported that the same mixture reduces the incidence of atopic
dermatitis during the first 6 months of their life. These investigators
also showed that the number of bifidobacteria in the GOS/FOS group
increased significantly suggesting that the change in faecal flora has
a positive role in the development of the immune system.
Human studies in patients
Whereas it is difficult if not impossible to show improved immune
functions in healthy people, studies with patients with colonic
disorders offer an attractive way of investigating the effects of
prebiotics on the immune status.
Studies in patients with inflammatory bowel disease (Crohn's disease,
CD or ulcerative colitis, UC) show encouraging, but not totally
unequivocal results. Casella et al. (27) found a significant reduction of
faecal calprotectin (a marker for mucosal inflammation) in UC patients
consuming 12 g/d of an inulin/oligofructose mixture, but no difference
in disease activity versus placebo. With CD patients it was shown that
15 g/d of FOS decreased disease scores together with an increase of
faecal bifidobacteria (28).
It may be that synbiotic treatment (using the combination of a
prebiotic with a probiotic bacterium) is also effective. E.g. in a case
study with inulin (15 g/d) in combination with B. longum a paediatric
UC patient remained in remission and could stop medical treatment at
least for a year (29, see also 30).
A possible complication of a colectomy is an inflammation of the ileal
reservoir (pouchitis). A study by Welters et al. (31) indicates that inulin
may be beneficial under these conditions. These investigators gave
24 g/d of inulin to potential pouchitis patients. This treatment not only
decreased histological inflammation scores but it also increased
butyrate concentrations and induced a lowering of the pH, as well as
less secondary bile acids and a lower number of Bacteroides fragilis.
No effect on the level of bifidobacteria and lactobacilli was found.
INULIN AND RESISTANCE TO GASTROINTESTINAL
The data described above show effects of inulin on various
parameters of the immune system. This part describes the effects of
inulin as measured by resistance against infections, i.e. whether the
immunemodulation depicted above actually leads to an improved
performance of the immune system. Animal trials showed that with 10
percent inulin and oligofructose in the feed the effects of systemic
infections with Listeria monocytogenes, Salmonella typhimurium and
Candida albicans in rats survival increased (32). Long chain inulin
seemed more effective than oligofructose in these trials, especially
with the Listeria infections. Interestingly also in weanling puppies
inulin supplementation reduced the effects of a Salmonella challenge:
with inulin, body weight changes and body temperature increases
after infection were less (33). And in poultry it was found that inulin
consumption may lower infections with Salmonella (34).
Data for humans are scarce, but Cummings et al. (35) showed that
travellers to high-risk countries had a trend for lowered occurrence of
diarrhoea with oligofructose consumption of 10 g/d. Later analysis of
the data showed that the severity of diarrhoea was significantly lower
with oligofructose consumption. Lewis et al. (36) looked whether
oligofructose (12 g/d) could prevent antibiotic-associated diarrhoea.
Although they found an increase in bifidobacteria in the faeces of the
patients, they did not find any protective effect of oligofructose
consumption in these elderly people. There are some data from
studies in children that also show encouraging results. Whereas
Duggan et al. (37) could not find an effect on diarrhoea prevalence
from oligofructose consumption in Peruvian infants, others (38)
showed that FOS consumption lowered the risk for diarrhoeal
infections in children of about 6 months in Indonesia.
vol 19 n 3 May/Jun 2008 Ag roFOOD industry hi-tech
Figure 2. Microbiota-dependent mechanisms of inulin induced immune
modulation (adapted from 50)
fermentable fibres, such as pectins or β-glucans. The review by Vos
et al. (50) provides an excellent overview of the immune modulating
effects of other nondigestible carbohydrates.
REFERENCES AND NOTES
1. B. Watzl et al., Br. J. Nutr., 93(Suppl. 1), pp. S49-S55 (2005).
2. P.D. Schley, C.J. Field, Br. J. Nutr., 87 (Suppl. 2), pp. S221-S230
3. B.C. Tungland, D. Meyer, Compr. Rev. Food Sci. Food Safety, 3, pp.
4. K. Yamada et al., Biosci. Biotechnol. Biochem., 67, pp. 429-433
5. S.J. ten Bruggencate et al., Gut, 53, pp. 530-535 (2004).
6. M. Roller et al., J. Nutr., 134, pp. 153-156.
7. S. Videla et al., Am. J. Gastroenterol., 96, pp. 1486-1493 (2001).
8. C. Cherbut et al., J. Nutr., 133, pp. 21-27 (2003).
9. F. Lara-Villoslada et al., Eur. J. Nutr., 45, pp. 418-425 (2006).
10. F. Hoentjen et al., Inflamm. Bowel Dis., 11, pp. 977-985 (2005).
11. A.M. Neyrink et al., J. Nutr., 134, pp. 1124-1129 (2004).
12. F. Pierre et al., Cancer Res., 57, pp. 225-228 (1997).
13. F. Pierre et al., Carcinogenesis, 20, pp. 1953-1956 (1999).
14. P.D. Cooper, M. Carter, Molec. Immunol., 23, pp. 896-901 (1986).
15. P.D. Cooper, E.J. Steele, Immunol. Cell Biol., 66, pp. 345-352 (1988).
16. K. Kerekes et al., J. Leukocyte Biol., 69, pp. 69-74 (2001).
17. M.H.M.C. van Nuenen et al., Microb. Ecol. Health Dis., 15, pp. 137-
18. H. Ito et al., J. Food Sci., 73, pp. H36-H41 (2008).
19. S. Fujitani et al., Allergol. Int., 56, pp. 131-138 (2007).
20. S.J.M. ten Bruggencate et al., J. Nutr., 136, pp. 70-74 (2006).
21. P.A. Scholtens et al., Br. J. Nutr., 95, pp. 1143-1149 (2006).
22. Y. Guigoz et al., Nutr. Res., 22, pp.13-25 (2002).
23. D. Bunout et al., J. Parenter. Enter. Nutr., 26, pp. 372-376 (2002).
24. F. Haschke et al., Monatsschr. Kinderheilk, 148, pp. S66-70 (2001).
25. M. Roller et al., Br. J. Nutr., 97, pp. 676-84 (2007).
26. G. Moro et al., Arch. Dis. Childh., 91, pp. 814-819 (2006).
27. F. Casellas et al., Aliment. Pharmacol. Ther., 25 pp. 1061-1067 (2007).
28. S. Lewis et al., Aliment. Pharmacol. Ther., 21, pp. 469-477 (2005).
29. N. Haskey, W. Dale, Nutr. Rev., 64, pp. 132-138 (2006).
30. E. Furrie et al., Gut, 54, pp. 242-249 (2005).
Readers interested in a complete list of references are kindly invited to write to the author
these fermentation products will be absorbed in the bloodstream they
will reach and affect other parts of the immune system as well.
Especially butyrate may be important as it affects chromatin structure
through inhibition of histone deacetylation (45), which in turn may
effect gene expression. Activation of immune cells of the GALT could
be mediated through activation of the recently described G-protein-
coupled SCFA receptors (e.g. 46).
Another point of interaction is possibly between prebiotics and
carbohydrate receptors on immune cells. It is known for instance that
soluble β-glucans from yeast cell walls can interact with receptors on
natural killer cells (47) and that certain receptors on neutrophils and
monocytes recognize a variety of β-glucans from fungi and plants
(48). Fructans receptors on immune cells have not yet been
described, but in vitro it has been shown that inulin can affect the
activity and proliferation of macrophages (49).
From the data presented above we can conclude that prebiotic fibres
such as inulin affect the immune system in various ways. It is also
clear however that more work will be required to fully assess the role
of inulin on immune activity. Systematic studies to determine the
effect of inulin on lymphocyte activity or other tests of immune
function are needed. To that end, relevant biomarkers have to be
found and their relationship with the immune status has to be
established. Results from such studies will certainly help to exploit the
potential for the application of inulin in functional foods in general, and
more specifically in functional foods to support the immune system or
to enhance immune function. This may be particularly relevant for
foods for the elderly with their lowered immune activity and for infant
foods in which immune development is of paramount importance.
Although the data presented above were confined to inulin and similar
prebiotics the mechanisms may be equally relevant for other
Agr oFOOD industry hi-tech May/Jun 2008 vol 19 n 3