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Cruciferous vegetables: Prototypic anti-inflammatory food components

November 2015
Clinical Phytoscience 1(1)

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There is increasing evidence that food components contribute to the pathogenesis of various disorders such as inflammatory bowel diseases, atherosclerosis, cancer or type 2 diabetes. Dietary factors especially enriched in Western diet cause and promote inflammatory processes throughout the organism involving various pathways but mainly the induction of pro-inflammatory cytokines. In contrast, there is increasing evidence that certain food components such as present in cruciferous vegetables have important anti-inflammatory properties. Cruciferous vegetables contain large amounts of various indole derivatives and are able via these components to activate aryl hydrocarbon receptors (AhR). Activation of these intracellular receptors results in potent intestinal immune modulation including regulation and maintenance of intestinal intraepithelial lymphocytes and innate lymphoid cells, induction of the key barrier cytokine interleukin-22 and manipulation of the intestinal microbiota. Lack of AhR is associated with an impaired barrier function and increased intestinal vulnerability suggesting that the continuous presence of dietary AhR ligands may be of importance throughout life. Sulforaphane, an isothiocyanate compound of cruciferous vegetables, also exerts mainly anti-inflammatory properties on immune processes. Therefore, evidence is accumulating that certain food components are healthy by targeting intestinal immune responses and reshaping the microbiota.

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R E V I E W Open Access

Cruciferous vegetables: prototypic

anti-inflammatory food components

Herbert Tilg

Abstract

There is increasing evidence that food components contribute to the pathogenesis of various disorders such as

inflammatory bowel diseases, atherosclerosis, cancer or type 2 diabetes. Dietary factors especially enriched in

Western diet cause and promote inflammatory processes throughout the organism involving various pathways but

mainly the induction of pro-inflammatory cytokines. In contrast, there is increasing evidence that certain food

components such as present in cruciferous vegetables have important anti-inflammatory properties. Cruciferous

vegetables contain large amounts of various indole derivatives and are able via these components to activate aryl

hydrocarbon receptors (AhR). Activation of these intracellular receptors results in potent intestinal immune

modulation including regulation and maintenance of intestinal intraepithelial lymphocytes and innate lymphoid

cells, induction of the key barrier cytokine interleukin-22 and manipulation of the intestinal microbiota. Lack of AhR

is associated with an impaired barrier function and increased intestinal vulnerability suggesting that the continuous

presence of dietary AhR ligands may be of importance throughout life. Sulforaphane, an isothiocyanate compound

of cruciferous vegetables, also exerts mainly anti-inflammatory properties on immune processes. Therefore,

evidence is accumulating that certain food components are healthy by targeting intestinal immune responses and

reshaping the microbiota.

Keywords: Anti-inflammatory; Carbazoles; Cruciferous plants; Isothiocyanates; Healthy food

Introduction

Diet is a well established risk factor for many disorders

ranging from inflammatory bowel diseases (IBD), type 2

diabetes, atherosclerosis and various cancers [1]. The

marked increase of many of these disorders has been

paralleled in the last decades by changing habits regarding

food consumption and overall industrialization. Epidemio-

logical studies have revealed that many inflammatory con-

ditions are associated with increased consumption of a

Western diet enriched in saturated fatty acids, carbohy-

drates, refined grains, processed red meat and a low con-

tent of vegetables, fruits and fish. This diet is increasingly

consumed worldwide and it is assumed that the spread of

such dietary behaviors has contributed significantly to

changing disease patterns as e.g. observed for IBD. Diets

enriched in vegetables and fruits such as the Mediterra-

nean diet have been proposed to provide health benefits

[2]. Therefore, dietary components overall might have a

major impact on disease pathogenesis and manifestation.

It is increasingly understood that dietary components

interact with the host mainly by affecting and shaping

the intestinal microbiota and immunity [3]. The inter-

action between food components and the gastrointes-

tinal tract involves several components of the immune

system including intestinal intraepithelial lymphocytes,

innate lymphoid cells, immune mediators, epithelial cells

and a heterogeneous group of immune cells including

dendritic cells [1]. Molecular pathways used by both

pathogens and dietary components such as the aryl

hydrocarbon receptor (AhR) could be an example for

understanding how diet affects and drives intestinal im-

munity [4–6]. The microbiota is the key factor determin-

ing development and maintenance of the intestinal and

systemic immune response [7, 8]. The diet controls the

dynamics and composition of the microbiota, and the re-

lationship diet −microbiota −immunity is essential for

human development and health. The contributions of

the intestinal microbiota to development of immunity

Correspondence: herbert.tilg@i-med.ac.at

Department of Internal Medicine I, Endocrinology, Gastroenterology &

Metabolism, Medical University Innsbruck, Innsbruck, Austria

License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any

medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons

license, and indicate if changes were made.

Tilg Clinical Phytoscience (2015) 1:10

DOI 10.1186/s40816-015-0011-2

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

and respective effects of dietary components on its com-

position are complex and beyond the scope of this re-

view. The adage “You are what you eat”is increasingly

supported by scientific evidence. This article will briefly

summarize aspects of pro-and anti-inflammatory food

components focusing on healthy aspects of cruciferous

vegetables.

Review

Inflammatory diets: potential mode of actions

The incidence of many chronic inflammatory disorders

has changed dramatically in the last three to four de-

cades. Many of those disorders such as IBD, rheumatoid

arthritis, metabolic syndrome, and atherosclerosis, are

characterized by continuous low-grade systemic inflam-

mation. In most of those diseases environmental factors

such as diet seem to play a major role as genetic factors

can only explain the minority of cases. Western diets

may promote inflammatory processes through various

mechanisms. Fatty acids support inflammation through

various mechanisms, including direct actions on im-

mune cells, toll-like receptors (TLRs), and cytokine sig-

naling, as well by affecting intestinal permeability [9, 10].

In healthy subjects, a high-fat Western diet results in

endotoxemia and may thereby lead to low-grade sys-

temic inflammation [11, 12]. A high fat diet (HFD) in-

duces intestinal inflammation and the expression of

tumor necrosis factor-alpha (TNF-α) in the ileum in

obesity, and this effect is only observed in conventionally

raised specific-pathogen free mice, but not in germ-free

mice [13]. As a Western diet is enriched in polyunsatur-

ated fatty acids (PUFA), this mechanism has also been

shown to contribute to intestinal inflammation especially

in older mice, as demonstrated by increased influx of

neutrophils and macrophages [14]. Importantly, Western

diet is especially enriched in n-6 PUFA and deficient in

n-3 PUFA and it is assumed that the ratio of n-6 to n-3

PUFA in Western diet is an issue but not PUFA in gen-

eral. Overall it can be concluded that Western diets

affect immunity, promote inflammation, and these effects

importantly also include major effects on the microbiota

and metabolome via many pathways. All these effects may

negatively influence human health and contribute to the

disease burden which is caused by consumption of an im-

balanced and rather “pro-inflammatory”Western diet. A

more extensive discussion of these “pro-inflammatory”as-

pects of diet is beyond the focus of this article.

Anti-inflammatory diets: Cruciferous vegetables

as prototypic proponents

Diet-derived indole derivatives as major activators of aryl

hydrocarbon receptors (AhR)

A main question remains what happens in humans when

they consume higher amounts of cruciferous vegetables.

Jiang and colleagues [15] have studied the effects of

vegetable intake in 1005 middle-aged Chinese women.

Indeed, an increased intake of cruciferous vegetables was

associated with decreased serum levels of the pro-

inflammatory cytokines IL-1β, TNFαand IL-6 support-

ing the concept of many in vitro studies that this type of

diet may have anti-inflammatory properties. As nutrition

contributes substantially to disease development, it re-

mains crucial and mandatory to better understand how

diets enriched in vegetables and fruits might constitute

anti-inflammatory effects. Aryl hydrocarbon receptor, a

transcription factor expressed by immune cells, epithelial

cells, and some tumor cells, has been identified as fun-

damental receptor for certain dietary components. In-

deed, in the last years many exogenous and endogenous

AhR ligands have been characterized—some derived

from foods such as broccoli, other include phytochemi-

cals, natural chemicals, and bacterial metabolites. Ligand

binding activates the AhR, resulting in its translocation

into the nucleus, where it dimerizes with the AhR nu-

clear translocator. This heterodimer regulates many

genes that control immunity and inflammation, such as

the important barrier cytokine IL-22, which has many

beneficial metabolic functions [16].

Several studies published in the last few years have

highlighted how dietary-derived AhR ligands affect local/

systemic immunity. Specific components of certain vege-

tables of the family Brassicaceae (for example, broccoli,

Brussel’s sprouts or cabbage) are physiologic ligands of

the AhR. Li et al. [5] observed that AhR signaling main-

tains numbers and functions of intraepithelial lympho-

cytes and innate lymphoid cells, and that AhR-deficiency

increased epithelial vulnerability and immune activation

in mice. AhR-deficiency furthermore affected the micro-

biota, and decreased intestinal production of granzymes

A and B, C-type lectins, and matrix metalloproteinase-7,

accompanied by a 4-fold increase in the proportion of

Bacteroidetes. Interestingly, absence of AhR ligands in-

creased severity of colitis in mice; when animals were

fed with diet enriched in AhR ligands, observed alter-

ations were reversed. Kiss et al. [6] showed that activa-

tion of AhR by dietary ligands is essential for post-natal

expansion of certain innate lymphoid cells and the de-

velopment of intestinal lymphoid follicles. Mice deficient

in AhR exhibited an impaired intestinal immunity and

were highly susceptible to infection with Citrobacter

rodentium. AhR ligands increased numbers of IL-22-

producing RORγt

intestinal lymphoid cells. These cells

contribute in a major fashion to gastrointestinal innate

immune functions such as the production of antimicro-

bial peptides and mucus and maintenance of epithelial

integrity. Also other studies have shown that AhR is re-

quired for the production of IL-22, supporting the im-

portance of this relationship [17]. The studies of Li et al.

Tilg Clinical Phytoscience (2015) 1:10 Page 2 of 6

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

[5] and Kiss [6] et al. provide evidence that some sort of

“dietary pattern recognition receptors”might exist that

link diet with intestinal immunity and the microbiota

(Table 1).

The pathway between AhR ligands and IL-22 is highly

relevant in the area of intestinal immunity and metabol-

ism. Administration of IL-22 diminished metabolic de-

fects and restored mucosal immunity to mice on HFDs,

as well as in leptin receptor-deficient (db/db) mice [16].

Overall, dietary factors that activate the AhR have the

capacity to affect expression of cytokines (particularly

IL-22), synthesis of certain mucins, production of anti-

microbial peptides, and consequently shape the intes-

tinal barrier and furthermore the composition of the

intestinal microbial community. Although findings of

these two major studies are solely based on preclinical

experimental data, they could have major clinical impli-

cations as (i) a continuous presence of beneficial dietary

antigens might be needed in the intestinal tract to main-

tain functionality of the immune system including toler-

ance throughout life and (ii) if oral supplementation of

such beneficial food components is interrupted such as

observed in intensive care patients undergoing long-

term parenteral nutrition this could severely impair local

immunity, barrier function and at the end contribute to

disease burden as observed in such patients.

Further beneficial examples for indole derivatives

Concentrations of carbazoles may be increased by other

dietary compounds such as quercetin, resveratrol, and cur-

cumin as demonstrated recently [18]. These compounds

induce cytochrome P4501A1 in an indirect manner by

inhibiting the metabolism of indole derivatives. Indole-3

carbinole (I3C) and its derivatives may also have benefi-

cial effects on bone metabolism. An acid-condensation

product of I3C, 3,3′-diindolymethane (DIM), prevents

ovariectomized-induced bone loss by suppressing osteo-

clastic bone resorption [19]. Although not studied, it can

be speculated that interference with the pro-inflammatory

cytokine milieu in the bone as observed in osteoporosis

might be one of those protective mechanisms. Adminis-

tration of DIM also suppressed the nuclear factor kappaB

(NF-κB) signaling pathway in microglia and protected cor-

tical neurons from inflammatory toxicity [20]. When

tested in mice, DIM attenuated LPS-induced brain inflam-

mation in mouse hippocampus. Interestingly, in this

model I3C did not show protective effects. When male

C57BL/6 mice received a HFD and were treated intraperi-

toneally with I3C for 12 weeks, this resulted in a profound

improvement of metabolic inflammation in adipose tissue

by the substantial decrease of macrophage infiltration and

their cytokine production [21].

Tryptophan: a dietary anti-inflammatory amino acid

The essential amino acid tryptophan is another nutrient

also found in cruciferous vegetables which shows anti-

inflammatory activities. Tryptophan is metabolized by

the microbiota, e.g. Lactobacilli, to indole-3-aldehyde,

another AhR agonist. This interaction is accompanied by

induction of IL-22, which affected the microbiota, pro-

viding resistance to colonization by Candida albicans

and protecting the mucosa against inflammation. This

study therefore nicely highlights how another beneficial

nutrient might results in gastrointestinal health again in-

volving the microbiota and various immune pathways

[22]. Tryptophan might exert anti-inflammatory effects

via additional pathways such, as after conversion to

kynurenine by indoleamine 2,3-dioxygenase (IDO). Both

kynurenine and IDO have immunomodulatory functions

that include promotion of regulatory T cells and

Table 1 Effects of anti-inflammatory diets on immunity

Anti-inflammatory Foods Microbiota-

dependent

Potential pathways Effects on Immunity References

cruciferous vegetables

(carbazoles)

AhR ligands

Suppression of NFκB

IL-22 ↑, maintenance of intraepithelial

lymphocytes and innate lymphoid cells,

suppression of inflammation

[5,6]

Cruciferous vegetables

and fish (tryptophan)

AhR ligands GPCRs IL-22 ↑, mucosal protection from

inflammation

[5,6,17]

cruciferous vegetables

(sulfarophane)

?Suppression of NFκB Suppression of inflammation, induction

of apoptosis, activation of phagocytosis

[23,24]

mediterrenian diet

(enriched in ω-3 fatty acids)

?Gpr120 pro-inflammatory cytokines ↓[43]

Abbrevations

AhR aryl hydrocarbon receptor

GPCRs G-protein coupled receptors

NFκBNuclear factor kappaB

Gpr G-protein receptor

SCFA short chain fatty acids

TH t helper cell

Diet results in an altered microbiota

Tryptophan metabolized by microbiota (e.g. lactobacilli) to indole-3 aldehyde and kynurenine (both AhR ligands)

Tilg Clinical Phytoscience (2015) 1:10 Page 3 of 6

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

regulation of immune tolerance. The tryptophan metab-

olite kynurenine is an additional tryptophan-derived lig-

and of the AhR. Beside indole derivates, several other

plant products, such as flavonoids and polyphenols, also

bind to the AhR —however with lower affinity. The

AhR therefore can be viewed as a major anti-

inflammatory factor that integrates dietary (“dietary pat-

tern recognition receptors”), microbial, metabolic, and

endogenous signals to alter the composition of the

microbiota and elicit protective immune reactions

(Table 1).

Other anti-inflammatory components of cruciferous

vegetables

Sulforaphane (SFN), an isothiocyanate compound of

cruciferous vegetables, protects from oxidative stress, in-

flammation and radiation injury. It inhibits LPS-induced

monocyte adhesion via suppression of intercellular adhe-

sion molecule-1 (ICAM-1) [23]. Furthermore, SCN also

suppresses NF-κB activity in LPS-stimulated endothelial

cells and these anti-inflammatory activities were dependent

on intracellular glutathione levels. Such an inhibitory ef-

fect could also be observed in mouse peritoneal macro-

phages [24]. Interestingly, this anti-inflammatory effect

was dependent on nuclear factor erythroid-2-related fac-

tor 2 (Nrf2) as it was not observed in Nrf2 (−/−) primary

peritoneal macrophages. Nrf2 activates the transcription

of more than 500 genes, most of which are protective and

anti-inflammatory. Therefore, regulation of Nrf2 by iso-

thiocyanates can be considered as an important aspect of

its anti-inflammatory capacities. Nrf2 has been discussed

to extend both healthspan and lifespan. Cruciferous vege-

tables can therefore be considered a diet with Nrf2-raising

and therefore highly beneficial properties.

SFN is able to inhibit TNF-α-induced NF-κB activation

through the inhibition of IκBαphosphorylation, IkBαdeg-

radation and p65 nuclear translocation [25]. This effect

was paralleled by induction of apoptosis through ac-

tivation of reactive oxygen species (ROS)-dependent

caspase-3. Importantly, and this supports a relevant anti-

inflammatory role for SFN, it also suppresses vascular cell

adhesion molecule (VCAM)-1 in LPS-stimulated endothe-

lial cells [26]. In these experiments, SFN decreased the

phosphorylation of extra-cellular signal-regulated kinase

(ERK), JUN N-terminal kinase (JNK) and p38 mitogen-

activated protein kinase (MAPK), all important inflamma-

tory signaling cascades. In addition, SFN also affected

TLR4 expression and suppressed MyD88, a key member

of the signaling machinery of TLRs and the IL-1 pathway.

Isothiocyanate suppresses LPS-induced synthesis of

interferon-inducible protein-10 (IP-10) and phosphoryl-

ation of interferon regulatory factor 3 (IRF3) in RAW 264.7

cells [27]. Therefore, beneficial and anti-inflammatory

effects of SFN might be mediated by various pathways

including modulation of Toll-interleukin-1 receptor

domain-containing adapter inducing interferon-beta

(TRIF) signaling pathway of TLRs. SFN also shows anti-

atherosclerotic activities as it inhibits endothelial lipase

(EL) activity in endothelial cells [28]. Endothelial lipase

is a member of the triacylglycerol lipase family released

during inflammation and has the capacity to decrease

high-density lipoprotein levels. Therefore, suppression

of EL by SCF could contribute to an important systemic

anti-inflammatory profile exerted by cruciferous vegeta-

bles (Table 1).

Overall, these data suggest that SFN and above described

mechanisms might contribute to anti-inflammatory proper-

ties of cruciferous vegetables. SFN also affects phagocyt-

osis capacity of macrophages as it raises the phagocytic

activity of RAW 264.7 murine macrophages [29]. Activa-

tion of phagocytosis remains an important mechanism to

reduce and clear inflammatory insults. Recently it has also

been shown that SFN inactivates macrophage migration

inhibitory factor (MIF), an important inflammatory cyto-

kine [30]. SFN is also protective in animal models of in-

flammation as it increases the survival of rats with hepatic

failure as achieved after administration of D-galactosa-

mine and LPS [31]. These effects were potentially achieved

by its potent capability to suppress synthesis of pro-

inflammatory cytokines such as TNF-αand Fas and ROS.

SFN has also chemopreventive properties. An excessive

expression of cyclooxygenase-2 (COX-2) links inflamma-

tion and cancer and SFN indeed suppresses COX-2 in

human mammary epithelial cells after stimulation with

12-O-tetradecanoylphorbol-13-acetate (TPA) [32]. These

effects were again mainly NF-κB- and ERK-mediated as

demonstrated in earlier studies.

Berteroin (5-methylthiopentyl isothiocyanate) is another

compound of cruciferous vegetables which is mainly

present in cabbage, rucola salad leaves and mustard oil.

Berteroin also decreases LPS-induced pro-inflammatory

cytokines in RAW 264.7 macrophages. In the mouse ear,

berteroin suppressed TPA-induced edema formation by

down-regulating COX-2, NF-κB and ERK [33]. These au-

thors suggested that this compound could be developed as

local anti-inflammatory agent.

Potential toxicological aspects of cruciferous

vegetables

Some earlier experimental studies have suggested that

indole derivatives might exert detrimental effects in-

cluding promotion of tumour development. High doses

of I3C, probably never achieved after consumption in

humans, exhibit a dose-dependent toxicity including a

decrease in hepatic reduced glutathione and severe neuro-

logical toxicity in mice [34]. In another study, I3C after ad-

ministration over 52 weeks showed a tendency for an

increase of liver adenomas in rats after challenge with

Tilg Clinical Phytoscience (2015) 1:10 Page 4 of 6

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

diethylnitrosamine and thyroid gland tumour incidence was

increased significantly [35]. Indole derivatives promoted at

high dietary levels aflatoxin B1—initiated hepatocarcino-

genesis in rainbow trouts, an effect which was explained by

the authors by the observed increase in estrogenic activities

and induction of P450 isoenzymes [36]. Another study

showed that I3C-treated rats developed fewer mammary

adenocarcinomas but with a greater average weight per

tumour per rat suggesting again that I3C might negatively

affect tumour growth [37]. I3C has also been shown to up-

regulate genes associated with signaling pathways for cell

growth and proliferation suggesting that at least in this

model I3C might result in a toxigenomic profile [38].

Human clinical data are not supportive of above ex-

perimental findings, although clinical trials focusing on

the intake on cruciferous vegetables are rare. A recent

meta-analysis suggested that consumption of cruciferous

vegetables may reduce the risk of ovarian cancer [39]. In

a large European cohort study, consumption of vegeta-

bles but not fruit was associated with a lower incidence

of hepatocellular carcinoma [40]. A pooled analysis of

three Italian case–control studies has demonstrated that

a mediterranian diet reduces endometrial cancer risk

[41]. A very large study from UK demonstrated that a

diet enriched in vegetables and fresh fruits reduced both

incidence of cardiovascular disease and cancer [42]. All

these studies are in support of beneficial effects of vege-

table consumption on human health, although more

studies specifically addressing the effects of indole deriv-

atives are needed.

Conclusions

There exists a crucial and exciting relationship between

food, immunity, and the microbiota. Many dietary com-

ponents affect these interactions. Dietary components

exert either dominantly pro-or anti-inflammatory effects

on the host. A healthy diet might contain a balanced

mixture of pro- and anti-inflammatory dietary compo-

nents. Knowledge in this field has increased dramatically

in the last years. Key dietary players and their potential

mechanisms have been characterized and how they

might act harmful or beneficial on the host. Interven-

tional studies have also demonstrated that dietary factors

have strong effects on the microbiota and thereby might

exert many immunomodulatory effects. However, it will

be important to perform respective clinical studies in the

next years to gain deeper mechanistic insights. Such stud-

ies could lead to development of functional foods, with

beneficial and even therapeutic effects on the immune sys-

tem. Therefore, food could in the future be used in clinical

medicine to prevent and treat various diseases.

Competing interests

The author declares that he has no competing interests.

Acknowledgement

We gratefully acknowledge secretarial help by Mrs. Stephanie

Federspiel-Kleinhans.

Financial support

Herbert Tilg is supported by the excellence initiative (Competence Centers

for Excellent Technologies - COMET) of the Austrian Research Promotion

Agency FFG: Research Center of Excellence in Vascular Ageing Tyrol,

VASCage (K-Project Nr. 843536) funded by the BMVIT, BMWFW, the

Wirtschaftsagentur Wien and the Standortagentur Tirol.

Received: 19 May 2015 Accepted: 20 July 2015

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Broccoli Sprouts and Their Influence on Thyroid Function in Different In Vitro and In Vivo Models

Article

Full-text available

Oct 2022

Broccoli sprouts are a super vegetable; however, they have possible negative effects on thyroid function, which is especially important for patients with hypothyroidism. As the data on this issue are scarce, this study aimed to determine the safety and possible beneficial effect of broccoli sprouts both in vitro and in vivo. The in vitro model comprised the evaluation of the impact of broccoli sprouts on normal and neoplastic thyroid cells and the determination of their anti-inflammatory and antioxidant (IL-6, TNF-alpha, NO, and SOD) potential in macrophages. The in vivo model concerned the histopathological analysis of thyroid glands in healthy rats and rats with hypothyroidism (induced by iodine deficiency or sulfadimethoxine ingestion) fed with broccoli sprouts. The results of our study indicated that broccoli sprouts decreased the viability of thyroid cancer cells and prevented inflammation. The results also confirmed the satisfactory safety profile of the sprouts, both in vitro and in vivo; however, a further in-depth evaluation of this problem is still needed. Information on the influence of brassica vegetables on thyroid function is of great importance in terms of public health, particularly when taking into account that the risk of iodine deficiency, hypothyroidism, and thyroid cancer in the global population is still increasing.

Kale supplementation during high fat feeding improves metabolic health in a mouse model of obesity and insulin resistance

Article

Full-text available

Aug 2021
PLOS ONE

Cruciferous vegetables have been widely studied for cancer prevention and cardiovascular health. Broccoli is the cruciferous vegetable whose phytochemistry and physiological effects have been most extensively studied. Kale (Brassica oleracea var. acephala) appears on lists of ‘healthiest, nutrient dense foods’ but, there is paucity of data on kale as a functional food. In a 12-week study, we tested the effect of curly green kale on high fat diet (HFD) induced obesity and insulin resistance, lipid metabolism, endotoxemia and inflammation in C57BL/6J mice fed isocaloric diets. Kale supplementation did not attenuate HFD diet induced fat accumulation and insulin resistance (P = ns; n = 9) but, it lowered serum triglycerides, low density lipoprotein (LPL) cholesterol and prevented HFD induced increases in systemic endotoxemia and inflammation (serum LPS and Ccl2) (P<0.01; n = 9). In adipose tissue, kale enhanced the expression of genes involved in adipogenesis (P<0.01; n = 9), reduced the appearance of histologic markers of inflammation, downregulated both the gene expression and protein expression of the adipose tissue specific inflammation markers CD11c and F4/80 (P<0.001; n = 9) and reduced the gene expression of a battery of chemokine C-C motif ligands (Ccl2, Ccl6, Ccl7, Ccl8, Ccl9) and chemokine C-C motif receptors (Ccr2, Ccr3, Ccr5). We conclude that kale vegetable protects against HFD diet induced dysfunction through mechanisms involving lipid metabolism, endotoxemia and inflammation.

The Effect of Cabbage (Brassica oleracea var. capitata L.) Extract on Macrophage and Blood Vessel Counts in Clean Wound Tissue of Male Rats (Rattus norvegicus)

Article

Full-text available

Jun 2023

Highlights : Cabbage extract application accelerates wound healing and has anti-inflammatory effect. Cabbage extract serves as an affordable source material for wound healing and anti-inflammation. Abstract Cabbage is a widely consumed vegetable known for its health benefits due to its rich nutrients and phytochemicals, especially phenolic compounds, which are known to have potent anti-inflammatory and antioxidant effects. This study aimed to investigate the effects of cabbage extract on wound healing by observing inflammatory responses in wound tissue. A total of 24 male rats were divided into four groups, with six rats in each group. The experiment was conducted for five days by administering cabbage extract to the treatment group and distilled water to the control group. Skin wound tissues were collected from all rats for histological observation by counting the number of macrophages and blood vessels. The results of the observation were analyzed statistically using an independent sample t-test with p<0.05. The results showed that the number of macrophages and blood vessels in the treatment group was significantly higher than the control group on the third day and significantly lower on the fifth day. In conclusion, the administration of cabbage extract can accelerate the inflammatory and proliferative phases of wound healing by promoting the migration of cells, including macrophages, resulting in accelerated angiogenesis. In addition, the decreased number of macrophages and blood vessels during the proliferative phase showed that the healing phase had reached a more advanced stage.

Fermenting kale (Brassica oleracea L.) enhances its functional food properties by increasing accessibility of key phytochemicals and reducing antinutritional factors

Article

Full-text available

May 2024

The properties of kale as a functional food are well established. We sought to determine how fermentation further enhances these properties. We tested different fermentation conditions: (i) spontaneous fermentation with naturally occurring bacteria, (ii) spontaneous fermentation with 2% salt, (iii) Lactococcus lactis, (iv) Lactobacillus acidophilus, (v) mixture of L. lactis and L. acidophilus, (vi) mixture of L. lactis, L. acidophilus, and Clostridium butyricum. We quantified selected bioactive components using high‐performance liquid chromatography (HPLC) and antinutritional factors using a gravimetric method and spectrophotometry. We then determined (i) the antioxidant capacity of the vegetable, (ii) anti‐inflammation capacity, and (iii) the surface microbiota composition by 16S sequencing. All fermentation methods imparted some benefits. However, fermentation with mixed culture of L. lactis and L. acidophilus was most effective in increasing polyphenols and sulforaphane accessibility, increasing antioxidant activity, and reducing antinutritional factors. Specifically, fermentation with L. lactis and L. acidophilus increased total polyphenols from 8.5 to 10.7 mgGAE/g (milligrams of gallium acid equivalent per gram) and sulforaphane from 960.8 to 1777 μg/g (microgram per gram) but decreased the antinutritional factors oxalate and tannin. Total oxalate was reduced by 49%, while tannin was reduced by 55%–65%. The antioxidant capacity was enhanced but not the anti‐inflammation potential. Both unfermented and fermented kale protected equally against lipopolysaccharide (LPS)‐induced inflammation in RAW 264.7 macrophages and prevented increases in inducible nitric oxide synthase (iNOS), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1 beta (IL‐1β), and interleukin‐6 messenger RNA (IL‐6 mRNA) expression by 84.3%, 62%, 68%, and 85.5%, respectively. Unfermented and naturally fermented kale had high proportions of sulfur reducing Desulfubrio and Proteobacteria usually associated with inflammation. Fermenting with L. lactis and/or L. acidophilus changed the bacterial proportions, reducing the Proteobacteria while increasing the genera Lactobacilli and Lactococcus. In summary, fermentation enhances the well‐known beneficial impacts of kale. Fermentation with mixed cultures of L. lactis and L. acidophilus imparts higher benefits compared to the single cultures or fermentation with native bacteria present in the vegetable.

Dietary patterns, lung function and asthma in childhood: a longitudinal study

Article

Full-text available

Mar 2023
RESP RES

Background Longitudinal epidemiological data are scarce examining the relationship between dietary patterns and respiratory outcomes in childhood. We investigated whether three distinct dietary patterns in mid-childhood were associated with lung function and incident asthma in adolescence. Methods In the Avon Longitudinal Study of Parents and Children, ‘processed’, ‘traditional’, and ‘health-conscious’ dietary patterns were identified using principal components analysis from food frequency questionnaires at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25–75% of FVC (FEF25–75) were measured at 15.5 years and were transformed to z-scores based on the Global Lung Function Initiative curves. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years. Results In multivariable-adjusted models, the ‘health-conscious’ pattern was positively associated with FEV1 (regression coefficient comparing top versus bottom quartile of pattern score 0.16, 95% CI 0.01 to 0.31, P for trend 0.04) and FVC (0.18, 95% CI 0.04 to 0.33, P for trend 0.02), while the ‘processed’ pattern was negatively associated with FVC (− 0.17, 95% CI − 0.33 to − 0.01, P for trend 0.03). Associations between the ‘health-conscious’ and ‘processed’ patterns and lung function were modified by SCGB1A1 and GPX4 gene polymorphisms. We found no evidence of an association between the ‘traditional’ pattern and lung function, nor between any pattern and FEF25–75 or incident asthma. Conclusions A ‘health-conscious’ diet in mid-childhood was associated with higher subsequent lung function, while a diet high in processed food was associated with lower lung function.

Radish (Raphanus Sativus): Potential antioxidant role of bioactive compounds extracted from radish leaves - A review

Article

Full-text available

Sep 2022

Radish (Raphanus Sativus) used against many toxicants as a natural drug, is a worldwide grown cruciferous root crop with root part the main edible organ and leave part, which in dried form are effective as functional foods. Radish (Raphanus Sativus) that exhibits variety of colors has rich content of vitamins, phenolic compounds, dietary fiber and Phyto-anthocyanin. Based on physico-chemical, nutritional, antioxidant and microbiological properties radish leaves are more nutritionally rich than roots. Leaves are premier source of phenol, flavonoid and have free radical hunting ability. The antioxidant biomarker compound Rutin has been identified only in radish leaves. Therefore the inclusion of Radish leaves in the human diet could have higher bioactive compounds especially flavonoid availability than roots. Conclusion: Consumption of radish leaves mostly discarded may present nutritional and medicinal value to human health especially due to their Antioxidant Activity. Moreover to develop novel functional products more exploration is required to approximate other bioactive compounds from the radish leaves. Keywords: Radish (Raphanus Sativus), bioactive compounds Antioxidants and Skin

Brassica Vegetables and Hypothyroidism

Chapter

Oct 2024

Ivan A. Ross

Consuming vegetables from the Brassica genus is not just a dietary choice but a health-conscious decision. The vegetables, rich in over 100 diverse β-thioglucoside-N-hydroxysulfates, known as glucosinolates, have been linked to myriad health benefits. When the glucosinolates interact with the enzyme myrosinase, typically after chewing, they form isothiocyanates, some immediately broken down to release a permanently charged thiocyanate ion. Glucosinolates’ enzymatic and non-enzymatic breakdown produces major isothiocyanates, thiocyanates, nitriles, indole-3-carbinol, and diindolylmethane dimers.

Food and Vegetables as Source of Phytoactives for Immunomodulation

Chapter

Aug 2022

Immunomodulation deals with the alteration in immune responses under certain circumstances, and this is led by key molecules known as immunomodulators. Immunomodulators may be immunostimulators (involved in increase in response of immune system) or immunosuppressive (decreases the response of the immune system). It is of utmost importance that the function of the immune system is regulated to protect the human body against diverse ailments such as viral, cardiovascular, cancer and chronic inflammatory diseases. Recent studies reveal that certain foods have immunomodulatory properties that aid in the prevention of infection, and therefore, addition of diverse food in regular diet provides a wide spectrum of immunity. The most active constituents of food are vitamins, minerals, carotenes, flavonoids, etc. which provide health-promoting effects. Several vegetables such as spinach, celery, carrots, broccoli, etc. have been studied intensively for their immunomodulatory activity. Similarly, parsley, thyme, oregano and coriander, which are used as garnishing and as flavouring enhancer, are reported to control cytokine and chemokine responses. Recently, prebiotics, probiotics and various oligosaccharides and some essential oils have also been reported to have incredible immunomodulatory activities associated with their phenolic components. Proteins and protein hydrolysate derived from different foods (soybean, milk, fish, egg, rice, pea, spirulina, etc.) are also being investigated by researchers for their immunomodulatory effects. Here, in this chapter, we provide a detailed analysis of the immunomodulatory effects of different nutritional components of food and vegetables, with the probable mechanism of action.KeywordsCytokineImmunityImmunomodulationFoodsVegetables

Microorganisms in the Pathogenesis and Management of Ankylosing Spondylitis

Chapter

Jan 2022

Ankylosing spondylitis (AS) is a chronic systemic auto-inflammatory disease that mainly affects sacroiliac joints and the axial skeleton. AS shows the highest genetic association to human leukocyte antigen B27 (HLA-B*27) among the SpA family of diseases. While this link has been discovered many decades ago, the etiopathology of AS and the pathogenic role of HLA-B*27 in disease development remain to be fully elucidated. Increasing evidence supports the hypothesis that HLA-B*27-dependent diseases, such as, have an underlying microbial pathogenesis. This chapter discusses the causal mechanisms underlying disease pathogenesis in animal models and patient studies including the role of pathobionts in contributing toward HLA-B*27-associated AS. The chapter further discusses the current therapeutic approaches and the various emerging approaches of therapeutic modalities including prebiotics/probiotics, diet, targeted antibiotics, and microbial metabolites. As our understanding of the complex host-microbe interactions in AS improves, this may spur the development of new therapeutic avenues for AS and other HLA-B*27-associated diseases using approaches that target gut microbiota composition and function.KeywordsAnkylosing spondylitisSpondyloarthropathyHLA-B27MicrobiomeDysbiosisProbioticERAP1ERAP2Interleukin-23

Screening of the AhR- and Nrf2-linked transcriptional activities of some cruciferous vegetables and nuts in human intestinal epithelial cells as foods containing endogenous AhR ligand precursors

Article

Apr 2022

Gamze Toydemir

Cruciferous vegetables and nuts are rich in indole-3-carbinol (I3C) and L-tryptophan (L-Trp), respectively, which can be converted upon ingestion into AhR ligands. Activation of AhR by dietary ligands contributes to unlocking its therapeutic potential in gastrointestinal homeostasis. In this study, some cruciferous vegetables (cabbage (red and white), cauliflower) and nuts (sunflower seed kernel, pistachio, cashew, walnut) were investigated for their effects on AhR- and Nrf2-mediated gene expression by using an in vitro digestion/Caco-2 cell culture model. Nuts induced AhR-pathway in a directly proportional manner with their L-Trp contents (sunflower induced the highest (5.3-fold) CYP1A1 expression). Nuts also showed Nrf2-dependent activities, although L-Trp standard did not. Vegetables activated only AhR-pathway, same with I3C standard, and red cabbage induced the highest CYP1A1 expression (9.6-fold). Results suggested the contribution of L-Trp and I3C in AhR-dependent activities of nuts and vegetables, respectively, although there appeared other bioactives to be identified in overall health aspects of these foods.

Mediterranean diet and risk of endometrial cancer: A pooled analysis of three Italian case-control studies

Article

Full-text available

May 2015
BRIT J CANCER

Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study

Article

Full-text available

Mar 2015

Background: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice

Article

Full-text available

Jan 2015
J PHARMACOL SCI

3,3'-Diindolylmethane (DIM), a major acid-condensation product or metabolite of indole-3-carbinol which is found in cruciferous vegetables, has been shown to have anticancer, anti-inflammatory, and multiple immune stimulating effects. However, its function in bone metabolism is poorly understood. This study evaluated the effect of DIM on bone mass in mice under physiological and pathological conditions. Eight-week-old female mice received injections of a vehicle or 0.1mg/g of DIM, twice a week for four weeks. We found that DIM treatment significantly increased bone mass as assessed by dual-energy X-ray absorptiometry (DEXA) and micro-computed tomography (μCT). Further, Bone histomorphometric analyses showed that this treatment significantly reduced bone resorption parameters, but did not increase bone formation parameters. Furthermore, we use ovariectomized (OVX)-induced osteoporotic mouse model, and explore function of DIM in skeletal pathological processes. Bone phenotype analyses revealed that the administration of DIM in this study effectively prevented OVX-induced bone loss resulting from increased bone resorption. Our results demonstrated that DIM increased bone mass by suppressing osteoclastic bone resorption in bone metabolism under both physiological and pathological conditions. Accordingly, DIM may be of value in the treatment and the possible prevention of bone diseases characterized by bone loss, such as postmenopausal osteoporosis. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Berteroin Present in Cruciferous Vegetables Exerts Potent Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin

Article

Full-text available

Nov 2014

Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.

The Aryl Hydrocarbon Receptor Meets Immunology: Friend or Foe? A Little of Both

Article

Full-text available

Oct 2014

The aryl hydrocarbon receptor (AHR) has long been studied by toxicologists as a ligand-activated transcription factor that is activated by dioxin and other environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs). The hallmark of AHR activation is the upregulation of the cytochrome P450 enzymes that metabolize many of these toxic compounds. However, recent findings demonstrate that both exogenous and endogenous AHR ligands can alter innate and adaptive immune responses including effects on T-cell differentiation. Kynurenine, a tryptophan breakdown product, is one such endogenous ligand of the AHR. Expression of indoleamine 2,3-dioxygenase by dendritic cells causes accumulation of kynurenine and results in subsequent tolerogenic effects including increased regulatory T-cell activity. At the same time, PAHs found in pollution enhance Th17 differentiation in the lungs of exposed mice via the AHR. In this perspective, we will discuss the importance of the AHR in the immune system and the role this might play in normal physiology and response to disease.

Sulforaphane increases the survival rate in rats with fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide

Article

Full-text available

Nov 2014
NUTR RES

Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome, with liver transplantation being the only effective therapy. Sulforaphane (SFN) is a natural compound that is extracted from cruciferous vegetables and possesses potent anti-inflammatory, antioxidant, and anti-cancer activities. This study was designed to test the hypothesis that SFN (3 mg/kg) may protect against FHF induced in rats by administering a combination of D-galactosamine (GalN; 300 mg/kg) and lipopolysaccharide (LPS; 30 μg/kg). The rats were given a single intraperitoneal injection of SFN, one h before the FHF induction. SFN reduced the mortality and alleviated the pathological liver injury. In addition, SFN significantly reduced the increase in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in the GalN/LPS group, and this decrease was attenuated by SFN. Increases in serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10, which were observed in GalN/LPS-treated rats, were significantly reduced after using SFN. The GalN/LPS treatment increased the expression of superoxide dismutase-1, glutathione peroxidase 2, catalase, and heme oxygenase-1 genes. SFN inhibited the induction of reactive oxygen species scavenging proteins. Moreover, SFN inhibited GalN/LPS-induced caspase-3 activation and suppressed FAS and FASL expression. These findings suggest that SFN alleviates GalN/LPS-induced liver injury, possibly by exerting antioxidant, anti-inflammatory, and anti-apoptotic effects and modulating certain antioxidant defense enzymes.

Dietary influences on intestinal immunity

Article

Sep 2012
NAT REV IMMUNOL

The function of the gastrointestinal tract relies on a monolayer of epithelial cells, which are essential for the uptake of nutrients. The fragile lining requires protection against insults by a diverse array of antigens. This is accomplished by the mucosa-associated lymphoid tissues of the gastrointestinal tract, which constitute a highly organized immune organ. In this Review, we discuss several recent findings that provide a compelling link between dietary compounds and the organization and maintenance of immune tissues and lymphocytes in the intestine. We highlight some of the molecular players involved, in particular ligand-activated nuclear receptors in lymphoid cells.

Intake of cruciferous vegetables is associated with reduced risk of ovarian cancer: A meta-analysis

Article

Mar 2015
ASIA PAC J CLIN NUTR

Epidemiological studies on the association between cruciferous vegetable (CV) consumption and the risk of ovarian cancer have demonstrated inconsistent results. We conducted a meta-analysis on CV consumption and ovarian cancer risk. The relevant studies were identified by searching the Medline (Pubmed), Embase and Web of Science databases. The references of related articles and reviews up to October 2013 were also screened. The pooled relative risks (RRs) with 95% confidence intervals (CIs) for the highest versus the lowest CV consumption levels were calculated using a random-effects model. The heterogeneity and publication bias were also evaluated. Eight studies (4 case-control studies and 4 cohort studies) were identified and included in this meta-analysis. When all studies were pooled together, there was a significantly inverse association between CV consumption and the risk of ovarian cancer (RR: 0.89; 95% CI: 0.81-0.99). No significant heterogeneity or publication bias was found. The findings from this study suggest that the consumption of CVs may reduce the risk of ovarian cancer. Further investigations are needed to confirm the clinical effect of CVs on ovarian cancer.

Food, Immunity, and the Microbiome

Article

Jan 2015

There is increasing evidence that ingested diet-borne components areinvolved in the pathogenesis of disorders such as inflammatory bowel diseases, atherosclerosis, and type-2-diabetes. Nutrients can have short- and long-term effects in shapingthecompositionof the microbiota. Western diets (enriched in fat, phosphatidylcholine, and L-carnitine)promote inflammation and atherosclerosis through specific fatty acids and degradation products such astrimethylamineN-oxide. Other dietary factors such as carbazoles or tryptophan-enriched proteinshave anti-inflammatory properties-partly via activation of aryl hydrocarbon receptors. The microbiota and its metabolic machinery produce a myriad of metabolites that serveas important messengers between the diet, microbiota, and host. Short-chain fatty acids affect immune responses and epithelial integrity via G-protein coupled receptors and epigenetic mechanisms. By increasing our understanding of interactions between diet, immunity, and the microbiota, we might develop food-based approaches to prevent or treat many diseases. There is now scientific evidence to support theadage "we are what we eat", and this process begins in early life. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes

Article

Aug 2014

The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established. Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine. Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases.