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Nutritional management of inflammatory bowel disease; an overview of the

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 Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102440

Contents lists available at ScienceDirect

Diabetes & Metabolic Syndrome: Clinical Research & Reviews

journal homepage: www.elsevier.com/locate/dsx

Nutritional management of inflammatory bowel disease; an overview

of the evidences
Nava Morshedzadeh a, Mehran Rahimlou b, Shabnam Shahrokh c, Parvin Mirmiran d, *,
Mohammad Reza Zali c
a
Department of Nutrition, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran
b
Department of Nutrition, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
c
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
d
Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Background and aims: Inflammatory bowel disease (IBD) is a chronic relapsingeremitting systemic
Received 1 September 2021 disease and one of the most common gastrointestinal diseases that affect many people. This review
Received in revised form designed to report the latest findings on the association between some nutrients and IBD.
17 February 2022
Methods: A review was performed to summarize the effect of various aspects of nutrition and diet on
Accepted 21 February 2022
clinical course, the severity of disease, intestinal epithelial inflammation, inflammatory and oxidative
stress markers. Literature searches were conducted in PubMed and Google Scholar up to June 27, 2021.
Keywords:
Results: Various studies have shown that an unhealthy diet and deficiency of some nutrients are involved
Inflammatory bowel disease
Nutrition
in the etiology of IBD. It has also been shown that intestinal dysbiosis can increase the risk of developing
Vitamin D IBD. The results of some studies have shown that supplementation with some nutrients such as omega-3
Probiotic polyunsaturated fatty acids and vitamin D and probiotics may have beneficial results in patients with
Diet IBD. Adherence to some restrictive diets has also been helpful in some studies.
Conclusions: Following proper nutritional approaches can play an essential role in managing IBD
symptoms. Further studies are needed to substantiate some of these findings.
© 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.

1. Introduction
Inflammatory bowel disease (IBD) is an idiopathic disease
caused by a dysregulated immune response to the host intestinal
microflora. Crohn's disease (CD) and ulcerative colitis (UC) are the
principal types of inflammatory bowel disease.
IBD has traditionally been considered adisease of high-income
nations, but the incidence of IBD in newly industrialized coun-
tries in South America, Asia, and Africa has risen over the past
decade to become a global disease [1,2]. The prevalence of IBD for
all age groups were estimated to be 505 per 100,000 and 322 per
100,000 population in Europe and 249 per 100,000 and 319 per
100,000 populations in North America for UC and CD, respec-
tively [3].
* Corresponding author. No.24, Shahid Arabi St.Yemen Blvd, Chamran Exp, Teh-
ran, P.O.Box: 19395-4763, Postal Cod:19857-17413, Iran.
E-mail address: parvin.mirmiran@gmail.com (P. Mirmiran).
Studies have shown that the prevalence of IBD in urban areas of
China is higher than in rural areas, which can be due to factors such
as urbanization, mortality rates, as well as environmental factors,
especially diet [4]. Although, the highest rates of IBD are assumed to
be in developed countries, and the lowest is considered to be in
developing regions, new research on the future epidemiology of IBD
has been shown in North Africa and the Middle East, a 2.3-fold
increment in prevalence is expected from 2020 to 2035. In India,
the prevalence of IBD cases has changed from 212.451 thousand
cases in 2017 to 550 thousand cases in 2020, which will experience a
prevalence of about 2.2 million patients in 2035 [5]. Low-income
countries like Nepal lacks a national IBD patients registry. In addi-
tion, countries with lower-middle-income status conduct limited
population-based studies to assess the prevalence and incidence of
IBD. One study in Nepal reported 23.7 and 1.6 per 1000 colonos-
copies per year for the incidence of UC and CD, respectively [6].
IBD is an idiopathic immune disease of unclear etiology. Com-
plex factors are involved in the pathogenesis of IBD; however it
appears that it may be a combination of diet, environmental factors,

https://doi.org/10.1016/j.dsx.2022.102440
1871-4021/© 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.
N. Morshedzadeh, M. Rahimlou, S. Shahrokh et al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102440

immunologic factors, infectious agents, genetic susceptibility, and
the microbiome [7].
IBD is characterized by chronic or relapsing immune system
activation and inflammation in the gastrointestinal (GI) tract, in
which a marked immune disorder causes epithelial barrier
dysfunction.
Several studies have highlighted the role of the cytokine re-
sponses in the intestinal immune system, with active dendritic cells
(DCs) and macrophages secreting such as tumor necrosis factor-
alpha (TNF-a), interleukin-1b (IL-1b), interleukin-6 (IL-6), which
actively regulate the inflammatory response in IBD. Therefore,
modulation of the immune system is a treatment strategy in this
disease [8].
Evidence suggests that dietary patterns might act as environ-
mental triggers in the development of Crohn's disease and ulcera-
tive colitis, in addition dietary pattern a critical role in the clinical
care of patients with IBD [9].
Several studies have been conducted to evaluate the efficacy of
nutrients in IBD patients. In some of them, there is a link between
anti-inflammatory compounds in the dietary pattern and disease
activity, mortality, disease severity, and risk of recurrence. We
briefly review the potential role of specific dietary compounds as an
anti-inflammatory factor in inflammatory bowel disease. Table 1
shows a summary of this review.
2. Omega-3 polyunsaturated fatty acids
Various epidemiological investigations have reported the
importance of dietary fats, including monounsaturated fatty acids
(MUFA) or polyunsaturated fatty acids (PUFA), in the progression of
UC and CD. High intake of linoleic acid (LA, n-6) is known as a risk
factor in accelerating the progression of both diseases. In contrast,
adequate intake of docosahexaenoic acid (DHA) and eicosa-
pentaenoic acid (EPA) can be a deterrent to the progression of these
diseases [7]. It has been reported that omega-3 fatty acids can affect
the peroxisome proliferator-activated receptor/nuclear factor of
activated T cells (PPAR-g/NFAT) and aids in healing intestinal mu-
cosa [10e13]. Also, results of an animal study revealed that
administration of diets with a higher amount of omega-3 fatty acids
could reduce the expression of COX-2 (cyclooxygenase-2) in the
colon and reduce the IL-6 and TNF-a production [14]. In another
experimental study on rats, Mbodji et al., showed that co-
administration of n-3 polyunsaturated fatty acids (n-3 PUFAs)
with 5-ASA (5-aminosalic acid) therapy was significantly more
effective in suppression of nuclear factor kappa B (NF-kB) activation
than 5-ASA alone. They also found that co-administration of n-3
PUFAs with 5-ASA also reduced this dose [14]. Mozaffari et al. in a
systematic review and meta-analysis of 12 studies with 282610
participants reported that there was an inverse association be-
tween dietary intake of long-chain n-3 PUFAs and the risk of UC.

Table 1
A summary of studies included in the review.

Author and Country Participants Study design Outcome measures Key Results
Year (Ref) and
characteristics

Morshedzadeh Iran 90 patients with Clinical trial Effect of flaxseed supplementation on hs-CRP, Reduction in hs-CRP and Mayo score
N et al., 2021 mild to moderate UC Mayo score, quality of life, IL-10, mRNA - increased in quality of life
[23] expression level of TLR4 - A significant increase in IL-10
- Decrease in Mayo score
- No difference was observed in mRNA expression
level of TLR4
Chicco F et al., Italy 165 IBD patients Randomized Investigating the effect of the Mediterranean Adherence from MED diet led to a significant
2020 [32] control trials diet on CDAI and Mayo score, endoscopy and/or improvement in liver steatosis, BMI, disease
CT- or MRI, weight, BMI, visceral fat, lean body severity and waist circumference
mass
Bjarnason I UK 81 patients with UC Randomized, Evaluation of the effect of probiotic No significant differences were observed in IBD-
et al., 2019 and 62 patients with double-blind, supplementation on Quality of Life, faecal QOL scores and laboratory data between placebo
[43] CD placebo- calprotectin and the probiotic groups.
controlled trial
Morshedzadeh Iran 90 patients with Clinical trial Effect of flaxseed supplementation on serum IL- Reduction in fecal calprotectin, Mayo score, ESR,
N et al., 2019 mild to moderate UC 6, INF-g, TGF-b, ESR INF-g, IL-6, waist circumference
[22] - fecal calprotectin - significant increase in TGF-b and IBDQ-9 score
- IBDQ-9 score
Khalili H et al., Sweden 83147 Adult prospective Incident cases of CD and UC A higher MED score was associated with a lower
2019 [31] participants (age cohort risk of CD (Ptrend ¼ 0.02). No significant
range: 45e79 years), association was observed between MED score and
45906 men risk of UC.
38095 women
Schreiner P Switzerland 1254 IBD patients prospective Comparison of the effectiveness of vegetarian There weren't any significant differences between
et al., 2019 cohort and gluten-free diets on the symptoms of colitis vegetarian and gluten free diets regarding disease
[48] and Crohn's activity, fistula, hospitalization or surgery rates.
Garg M et al., Australia Twenty-five patients Randomized Effect of Vitamin D on Intestinal Inflammation Reduction in faecal calprotectin levels in active UC
2017 [52] with IBD control trials and Faecal Microbiota No significant differences across the groups in
serum CRP
Karimi S et al., Iran 65 UC patients Randomized Effect of Vitamin D on serum levels of TAC, TOS Reduction in TOS level, no significant change in
2019 [53] control trials and 25- hydroxyl vitamin D (25-OHD) serum TAC, significantly increase in IBDQ-9 score
Holt P.R et al., USA Patients with Pilot clinical Effect of curcumin on CDAI, CRP, ESR, liver and - No changes in indexes of liver or renal function
2004 [72] Crohn's disease study renal function - Improved CDAI scores
Hanai H et al., Japan 89 patients with Randomized Effect of 2 g/day on clinical activity index (CAI) Curcumin improved both CAI and EI
2006 [73] remission UC control trials endoscopic index (EI)

Hs-CRP, high-sensitivity C-reactive protein; IL-10, interleukin-10; TLR4, toll-like receptors4; CDAI, crohn's Disease Activity Index; MED, mediterranean diet; QOL, IBD Quality
of Life Questionnaire; ESR, erythrocyte sedimentation rate; IL-6, interleukin-6; INF-g, interferon gamma; TGF-b, transforming growth factor beta; SCCAI, simple Clinical Colitis
Activity Index; TOS, total oxidant status; TAC, total antioxidant capacity; CD, crohn's disease; UC; ulcerative colitis.

2
N. Morshedzadeh, M. Rahimlou, S. Shahrokh et al.
Also, they found an inverse association between fish consumption
and the incidence of CD [15]. However, another review study did
not find sufficient evidence for the effectiveness of omega-3 sup-
plementation in patients with IBD [16].
Previous studies showed that n-3 PUFAs are substrates for some
inflammatory and anti-inflammatory eicosanoid production, such
as prostaglandins and leukotrienes. In fact, n-3 PUFAs, in compet-
itive inhibition, avoid the conversion of arachidonic acid to leuko-
trienes, lipoxins, and prostaglandins. They can also prevent
inflammation by blocking the synthesis of other inflammatory cy-
tokines and T-helper 1 (Th1) lymphocyte reactivity, as well as
leukocyte chemotaxis, adhesion molecule expression, and
leukocyte-endothelial adhesive interactions. Furthermore, it has
been reported that n-3 PUFAs are substrates to the synthesis of
resolvins, maresins, and protectins, indispensable in resolving
inflammation processes [17e19].
IBD patients may be deficient in essential fatty acids, and n-3
PUFAs interventions may help IBD patients by suppressing normal
cytotoxicity (modifying arachidonic acid compounds) and/or
reducing oxidative stress [20].
Despite the content described, due to the inconsistent results,
the European Society for Clinical Nutrition and Metabolism (ESPEN)
guidelines do not recommend the use of n-3 PUFAs supplements
among the patients with IBD [21].
3. Flaxseed as a source of ALA
Flaxseed is one of the richest plant sources of PUFA and active
compounds. Flaxseed contains high alpha-linolenic acid (ALA),
soluble fiber, and phytoestrogens. It has been reported that
inflammation and increased levels of inflammatory factors play an
essential role in the pathogenesis of IBD [22]. The results of some
animal and human studies showed that flaxseed or ALA supple-
mentation significantly reduced the Interferon gamma (IFNg), TNF-
a, IL-6, NF-kB, and intestinal permeability [23,24]. In our previous
study, the results showed that supplementation with grounded
flaxseed and flaxseed oil significantly reduced the level of eryth-
rocyte sedimentation rate (ESR), INF-g, IL-6 and significantly
increased the serum levels of transforming growth factor-beta
(TGF-b) [25]. Also, we found that grounded flaxseed supplemen-
tation caused a significant improvement in the interleukin-10 (IL-
10) gene expression. TGF-b, a protein regulating macrophage
functions and promoting the resolution of the UC, is increased by
flaxseed supplementation [26]. An important part of the beneficial
effects of flaxseed may be its high n-3 PUFAs content, phenolic
compounds, and soluble fiber [27,28].
4. Mediterranean diet
The Mediterranean has traditionally followed a diet rich in plant
foods; high consumption of vegetables, fruits, olive oil, nuts, and
legumes, and a medium intake of fish, dairy products, a low con-
sumption of saturated fat [29].
Nutrients and foods also may interact as a dietary pattern to
influence IBD risk. Diet patterns likely influence IBD through
several interacting mechanisms. These include the effects on im-
mune responsiveness and inflammation, severity, and disease
symptoms [30]. Evidence suggests a role for the Mediterranean diet
in both prevention and treatment of IBD. The effects of several di-
etary patterns such as the Mediterranean diet (MD), saturated fatty
acid (SFA) or MUFA, or n-3 PUFA diets on biomarkers related to
inflammation have been studied. It has been concluded that the MD
can downregulate the expression of leukocyte adhesion molecules
[31], decrease in proinflammatory interleukins (IL-1, IL-6, and
interleukin-18 (IL-18)), TNF-a and its receptors, c-reactive protein
3
Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102440
(CRP) and chemoattractant molecules (MCP-1) [32].
Since IBD is characterized by chronic inflammation of the
gastrointestinal tract and elevated pro inflammatory mediators,
adherence to a MD is associated with improved disease severity
[33].
Two large prospective cohort studies have shown that greater
adherence to a Mediterranean diet is inversely associated with risk
of later-onset CD but not UC in middle-aged men and women in
Sweden. These studies indicated that the higher MD score
compared to the lowest category of MD score was associated with a
lower risk of CD [34].
Among the parameters of the MD, fruit and vegetable, fer-
mented dairy, non-refined grains, and use of olive oil seem to have
the greatest effect in decreased risk of CD [34].
A long-term MD characterized by content high in a vegetable,
fruits, bread and cereals, olive oil and fish/seafood was associated
with reduction in inflammatory biomarkers and active disease;
moreover, any grade of liver steatosis was associated with adher-
ence to a MD in both UC and CD [35].
So, adherence to a MD is associated with reducing systemic
inflammatory burden acting simultaneously on different targets in
chronic diseases. On the other hand, the MD compared to the
western diet significantly reduces intestinal permeability and the
excessive influx of bacteria [35,36].
5. Gut microbiota and probiotic
It is believed that the human gut microbiota contains 500e1000
distinct bacterial strains and fungi and viruses [37]. In recent years,
much attention has been paid to evaluate the role of the intestinal
microbiome in the pathogenesis of various diseases. The gut
microbiome plays multiple roles in the body, such as participating
in the synthesis of specific vitamins, helping to regulate the im-
mune system, inhibiting the growth of pathogens, facilitating
digestion of dietary substrates, and regulating certain inflammatory
pathways [38]. The gut microbiota successfully protects the host
from bacterial infections by fighting with pathogens for resources
and creating bacteriocin, short-chain fatty acids (SCFA), particularly
butyrate, acetate, propionate, and hydrogen peroxide [39,40].
Various studies have shown that in patients with IBD, the
composition and frequency of bacteria in the gastrointestinal tract
change; in other words, dysbiosis is observed in these patients [41].
Also, a wide spectrum of microbial change was found, including a
decrease in variety, lower abundances of bacterial taxa within the
Phyla Firmicutes and Bacteroides, and rises in Gammaproteobac-
teria [42,43]. It has also been shown that in patients with IBD,
biodiversity and some bacterial strains, specially Firmicutes, Bac-
teroidetes, Lactobacillus, and Eubacterium, are reduced [42e44].
Due to the dysbiosis observed in patients with IBD, researchers
have focused on evaluating the role of probiotics in these patients
in recent years.
Derwae et al., in a meta-analysis study reported that there was
no benefit of probiotics over placebo in inducing remission in active
UC and CD. However, significant positive results were observed in
studies that used VSL#3 strains [45]. Bjarnason et al., in a ran-
domized controlled trial (RCT) study showed that multi-strain
probiotic supplementation for 4 weeks did not significantly
change the quality of life and laboratory data of patients with IBD.
However, the probiotic group showed a significant decrease in fecal
calprotectin (FCAL) in UC patients [46]. In another meta-analysis
study, it has been reported that probiotic supplementation had
no significant effects on children with CD. However, they found a
significant effect among patients with UC, especially after supple-
mentation with VSL#3 probiotics [47].
Studies related to the effectiveness of probiotics in patients with
N. Morshedzadeh, M. Rahimlou, S. Shahrokh et al.
IBD seem to be controversial, and further studies are needed.
However, supplementation with VSL#3 probiotics may have more
beneficial effects.
6. Gluten-free diet
The gluten-free diet is popular for managing the symptoms of
celiac disease. However, in recent years, the effects of this diet in
the management of some other diseases have also been evaluated.
Given that some patients with celiac disease show IBD-like symp-
toms and that a gluten-free diet is somewhat effective in managing
these symptoms, researchers are prompted to evaluate the effect on
IBD patients [48,49]. Comprehensive and cross-sectional studies
have been conducted on the prevalence of celiac disease, non-celiac
gluten sensitivity and gluten-free diet among patients with IBD.
The study discovered 0.6% of the diagnosis of celiac disease in the
group and also showed 4.9% of non-celiac gluten sensitivity. 19.1%
of those surveyed had previously tried a gluten-free diet and 8.2%
were currently on a diet. About two-thirds of individuals who
attempted a gluten-free diet indicated a reduction in gastrointes-
tinal symptoms, and 38.3% experienced fewer or less serious IBD
flares [50]. In another cohort study, the diets of more than 1,300
patients with IBD were evaluated. This study revealed that 4.7% of
those surveyed said they followed a gluten-free diet. Comparing
the clinical symptoms of this group with those who did not follow a
gluten-free diet, there was no significant difference in clinical
symptoms, length of hospital stay and disease severity between the
two groups. Surprisingly, IBD patients consuming a gluten-free diet
experienced poor overall psychological well-being [51].
It is clear that it is too early to judge the effectiveness of a gluten-
free diet in IBD patients, and further studies, especially interven-
tional studies, are needed to evaluate the effectiveness and possible
side effects of this diet.
7. Vitamin D
The prevalence of vitamin D deficiency in IBD is 30e40%.
Vitamin D insufficiency may increase the risk of inflammation,
clinical relapse, or flare-ups in patients [52].
The mechanistic basis link between IBD and vitamin D may be
partly explained by the role of vitamin D antibacterial response,
antigen presentation, and regulation of adaptive and innate im-
munity. Vitamin D can influence the gastrointestinal barrier func-
tion and regulate proteins associated with epithelial cell gap
junctions through its anti-inflammatory activity [53].
Actually, vitamin D has the potential role in the prevention and
treatment of IBD via effects on barrier function and normal
commensal bacteria homeostasis and modulation of proin-
flammatory cascades [54].
Studies have shown that vitamin D can affect the inflammatory
profile and severity of the disease in UC. Garg M et al. showed that
the Supplementation of 40,000IU of cholecalciferol weekly signif-
icantly reduced CRP and fecal calprotectin [55]. Another study
showed that in UC, serum Total Oxidant Status concentration
significantly decreased in 2000 IU/day dose of vitamin D. However,
total antioxidant capacity levels did not change significantly.
Moreover, this study indicated that the 2000 IU daily dose of
vitamin D can increase serum 25-hydroxyvitamin D (25-OHD)
concentration, reducing disease activity in UC patients with
vitamin D deficiency. Their results showed that oral doses of 2000
IU vitamin D3 daily were superior to the daily dose of 1000 IU
vitamin D3 and increased better serum 25-OHD concentration in
patients with UC [56].
Vitamin D receptor (VDR) polymorphism may contribute to
autoimmune disorders such as arthritis, multiple sclerosis, type 1
4
Diabetes & Metabolic Syndrome: Clinical Research & Reviews 16 (2022) 102440
diabetes, cancer [57]. It has been shown that variants of VDR can be
involved in susceptibility to IBD development, and there was a
strong association between VDR gene polymorphism (BsmI
(rs1544410), FokI (rs2228570), TaqI (rs731236), and ApaI
(rs7975232)) and the onset and relapse of IBD. However, the results
of studies in IBD patients are contradictory [58,59].
A case-control study conducted among Caucasian European
patients reported a significantly higher frequency of the TaqI
polymorphism (genotype “tt”) in CD patients compared with UC
[60]. On the contrary, another studies from multiple geographical
regions and countries reported a significant difference between the
Bb genotype of the BsmI variant and UC [61] and no association was
found for ApaI and BsmI gene polymorphism with CD [62].
VDR gene, as a pleiotropic gene, is associated with regulation of
T-lymphocytes dampening Th-1 cell function and cytokine path-
ways (IL-2 and IFN-g pathway); moreover, vitamin D down-
regulates the production of pro-inflammatory cytokines and the
induction of regulatory T cells (Treg) [63,64].
8. Polyphenols
Polyphenols are plant-derived dietary compounds that can
protect against oxidative stress by beneficial anti-inflammatory and
anti-oxidative effects in various cells. Dietary polyphenols such as
curcumin, resveratrol, phloretin, and luteolin modulate the im-
mune signaling reactions by pattern-recognition receptors (PRRs).
The major classes of PRRs are the membrane-bound Toll-like re-
ceptors (TLRs) and the nucleotide-binding oligomerization domain
(NOD)-like receptors (NLRs) induct signaling pathways of cytokines
and chemokines that initiate inflammatory reactions in IBD [62].
Quercetin, a natural polyphenol from apple, grapes, black tea,
green tea, red wine, etc., can reduce intestinal inflammation
severity in IBD by inhibiting TNF-induced NF-kB transcription fac-
tor activation and inhibition of TLR-4-mediated inflammatory re-
sponses [65,66].
Resveratrol is a stilbenoid polyphenol found in high concen-
trations in peanuts, grapes, blueberries that acts like an antioxidant
[67]. Studies suggested that resveratrol significantly suppressed
NF-kB activation in a dose-dependent manner and inhibited TLR4/
NF-kB and p65/mitogen-activated protein kinase (MAPKs)
signaling cascade, thereby inhibiting I-kappa-B (IKB) kinase-
mediated NF-kB activation [68,69].
Resveratrol downregulated the gene expression of proin-
flammatory cytokines IL-1, IL-6, and TNF-a and reduced the
expression of profibrotic factors such as IGF-1, TGF-1, and pro-
collagen types I and III [70]. Resveratrol modulates the TLR-
pathway through Toll/IL-1 receptor domain-containing adaptor
inducing IFN-b (TRIF) -dependent signaling by targeting TANK
binding kinase 1 (TBK1) and receptor-interacting protein 1 (RIP1) in
TRIF complex [68]. In addition, resveratrol acts as an antioxidant
and induces various antioxidant enzymes.
Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-
heptadiene-3,5-dione), is the main natural polyphenol found in
turmeric. Curcumin can attenuate the course of IBD primarily
owing to its effect on disruption of NF-kB activation [71].
A potent antioxidant, curcumin can scavenge reactive oxygen
species (ROS) in the intestine; it maintains the balance of oxidants
and antioxidants via inhibiting oxidative stress and reduces
mucosal neutrophil infiltration. Several studies have reported that
Curcumin administration protects intestinal health and colonic
morphology [72]. Curcumin downregulated TLR-4-MyD88
signaling by interfering with cysteine residue-mediated receptor
dimerization [73]. A recent report showed that curcumin amelio-
rated inflammation by inhibiting pro-inflammatory cytokine
release, COX-1, and inducible nitric oxide synthase (iNOS) activity
N. Morshedzadeh, M. Rahimlou, S. Shahrokh et al.
and activation of NF-kB [74]. In two other studies, it has been shown
that supplementation with curcumin in IBD patients has been
associated with the clinical activity index and severity of the dis-
ease as well as the endoscopic parameters, which could indicate the
importance of the role of this polyphenol in the improvement of
these patients [75,76].
9. Summary
Multiple factors play a role in the pathogenesis of IBD. These
may include diet, environmental factors, immunologic factors, in-
fectious agents, genetic susceptibility, and the microbiome. The
emergence of rapid increases in IBD incidence over the past several
decades in low-incidence parts of the world, such as China, South
Korea, and Puerto Rico, clearly points to the vital role that the
environment plays in disease development. Specifically, the intro-
duction of the Western diet (which is high in fat and protein and
low in fruits and vegetables) has been proposed to explain the in-
crease in IBD incidence.
Compliance with ethical standards
There is no conflict of interest to report for the present study.
Acknowledgements
This study was supported by the Research Institute of Endocrine
Sciences, Shahid Beheshti University of Medical Sciences, Tehran,
Iran.
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