Host-microbial crosstalk relies on "tuft" love.

How commensals influence intestinal immunity is incompletely understood. In this issue of Immunity, Eshleman et al. demonstrate that microbiota-derived butyrate restrains tuft cell development via HDAC3 modulation in intestinal epithelial cells, showing how microbial metabolites impact intestinal type 2 immunity.

Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study.

BACKGROUND AND AIMS: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming. IMPACT: Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.

Deletion of TNF in Winnie-APCMin/+ Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients. To address the axis between TNF and CRC development and progression, we depleted the Tnf from our previously established murine model of colitis-associated cancer (CAC), the Winnie-ApcMin/+ line. We characterized the new Winnie-APCMin/+-TNF-KO line through macroscopical and microscopical analyses. Surprisingly, the latter demonstrated that the deletion of Tnf in Winnie-ApcMin/+ mice resulted in an initial reduction in dysplastic lesion incidence in 5-week-old mice followed by a faster disease progression at 8 weeks. Histological data were confirmed by the molecular profiling obtained from both the real-time PCR analysis of the whole tissue and the RNA sequencing of the macrodissected tumoral lesions from Winnie-APCMin/+-TNF-KO distal colon at 8 weeks. Our results highlight that TNF could exert a dual role in CAC, supporting the promotion of neoplastic lesions onset in the early stage of the disease while inducing their reduction during disease progression.

Determination of Commercial Animal and Vegetable Milks' Lipid Profile and Its Correlation with Cell Viability and Antioxidant Activity on Human Intestinal Caco-2 Cells.

Lipids from milk are important nutritional components, although their health effects, especially for animal milks, are still questioned. Four types of commercial milks, two semi-skimmed animal milks (bovine and goat) and two vegetable ones (soy and rice), along with their total and free lipid fractions recovered by sequential centrifugation or by ethyl acetate extraction, respectively, have been analyzed. A higher antioxidant ability, reported as Trolox equivalent antioxidant capacity, was found for all raw milks compared to that of rice. This trend was confirmed, except for soy milk, as ROS reduction in Caco-2 cells. The free lipid fraction was shown to have the highest antioxidant potential in both chemical and biological tests. Moreover, goat and soy raw milks positively regulated Caco-2 cell viability after an inflammatory stimulus. This effect was lost when their total lipid fraction was tested. Finally, only the free lipid fraction from rice milk preserved the Caco-2 viability after LPS stimulation. Our data demonstrated that the lipid profile of each milk, characterized by GC-MS analysis, could contribute to dictate its biological effects, and, although additional in vitro and in vivo studies are needed, they could support the literature re-evaluating the health effects of animal-based versus plant-based milks in the intestinal cellular model.

Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCIIlowCD11c+CD11b+F4/80+ Cells.

Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1, and decreased IRF8 expression.

Winnie-APCMin/+ Mice: A Spontaneous Model of Colitis-Associated Colorectal Cancer Combining Genetics and Inflammation.

(1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with ApcMin/+ mice. (3) Results: The resulting Winnie-ApcMin/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie-ApcMin/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie-ApcMin/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.

Deletion of Stearoyl-CoA Desaturase-1 From the Intestinal Epithelium Promotes Inflammation and Tumorigenesis, Reversed by Dietary Oleate.

BACKGROUND & AIMS: The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces monounsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium, and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice. METHODS: We generated mice with disruption of Scd1 selectively in the intestinal epithelium (iScd1-/- mice) on a C57BL/6 background; iScd1+/+ mice were used as controls. We also generated iScd1-/-ApcMin/+ mice and studied cancer susceptibility. Mice were fed a chow, oleic acid-deficient, or oleic acid-rich diet. Intestinal tissues were collected and analyzed by histology, reverse transcription quantitative polymerase chain reaction, immunohistochemistry, and mass spectrometry, and tumors were quantified and measured. RESULTS: Compared with control mice, the ileal mucosa of iScd1-/- mice had a lower proportion of palmitoleic (C16:1 n-7) and oleic acids (C18:1 n-9), with accumulation of stearic acid (C18:0); this resulted a reduction of the Δ9 desaturation ratio between monounsaturated (C16:1 n-7 and C18:1 n-9) and saturated (C16:0 and C18:0) fatty acids. Ileal tissues from iScd1-/- mice had increased expression of markers of inflammation activation and crypt proliferative genes compared with control mice. The iScd1-/-ApcMin/+ mice developed more and larger tumors than iScd1+/+ApcMin/+ mice. iScd1-/-ApcMin/+ mice fed the oleic acid-rich diet had reduced intestinal inflammation and significantly lower tumor burden compared with mice fed a chow diet. CONCLUSIONS: In studies of mice, we found intestinal SCD1 to be required for synthesis of oleate in the enterocytes and maintenance of fatty acid homeostasis. Dietary supplementation with oleic acid reduces intestinal inflammation and tumor development in mice.

Application of Spray Drying Particle Engineering to a High-Functionality/Low-Solubility Milk Thistle Extract: Powders Production and Characterization.

Many natural compounds having antioxidant and anti-inflammatory activity are a potential target for new therapies against chronic inflammatory syndromes. The oral administration of functional herbal supplements may become a prevention strategy or therapy adjuvant for susceptible patients. A case study is our milk thistle (Silybum marianum) extract rich in silymarin complex. A water-soluble microencapsulated powder system was developed by a spray drying technique to improve the poor silymarin bioactivity after oral administration. Sodium carboxymethylcellulose (NaCMC) was employed as coating/swelling polymer matrix and sodium lauryl sulfate (SLS) as the surfactant (1:1:0.05 w/w/w). A H2O/EtOH/acetone (50/15/35 v/v/v) solvent system was used as liquid feed. The microsystems were capable of improving the in vitro dissolution and permeation rates, suggesting an enhancement of bioactivity after oral administration. The microsystems protect the antioxidant activity of silymarin after harsh storage conditions period and do not affect the anti-inflammatory properties of the raw extract (efficient already at lower concentrations of 0.312 mg/mL) to reduce dendritic cells (DCs) inflammatory cytokine secretion after lipopolysaccharide administration. This approach allows managing particle size, surface properties and release of bioactive agents improving the bioactivity of a herbal supplement and is also possibly applicable to many other similar natural products.

Polyphenol administration impairs T-cell proliferation by imprinting a distinct dendritic cell maturational profile.

Currently little is known as to how nutritionally derived compounds may affect dendritic cell (DC) maturation and potentially prevent inappropriate inflammatory responses that are characteristic of chronic inflammatory syndromes. Previous observations have demonstrated that two polyphenols quercetin and piperine delivered through reconstituted oil bodies (ROBs-QP) can influence DC maturation in response to LPS leading to a modulated inflammatory response. In the present study, we examined the molecular effects of ROBs-QP exposure on DC differentiation in mice and identified a unique molecular signature in response to LPS administration that potentially modulates DC maturation and activity in inflammatory conditions. Following LPS administration, ROBs-QP-exposed DCs expressed an altered molecular profile as compared with control DCs, including cytokine and chemokine production, chemokine receptor repertoire, and antigen presentation ability. In vivo ROBs-QP administration suppresses antigen-specific T-cell division in the draining lymph nodes resulting from a reduced ability to create stable immunological synapse. Our data demonstrate that polyphenols exposure can drive DCs toward a new anti-inflammatory molecular profile capable of dampening the inflammatory response, highlighting their potential as complementary nutritional approaches in the treatment of chronic inflammatory syndromes.

The Chelating Ability of Plant Polyphenols Can Affect Iron Homeostasis and Gut Microbiota.

In the past decades, many studies have widely examined the effects of dietary polyphenols on human health. Polyphenols are well known for their antioxidant properties and for their chelating abilities, by which they can be potentially employed in cases of pathological conditions, such as iron overload. In this review, we have highlighted the chelating abilities of polyphenols, which are due to their structural specific sites, and the differences for each class of polyphenols. We have also explored how the dietary polyphenols and their iron-binding abilities can be important in inflammatory/immunomodulatory responses, with a special focus on the involvement of macrophages and dendritic cells, and how they might contribute to reshape the gut microbiota into a healthy profile. This review also provides evidence that the axes "polyphenol-iron metabolism-inflammatory responses" and "polyphenol-iron availability-gut microbiota" have not been very well explored so far, and the need for further investigation to exploit such a potential to prevent or counteract pathological conditions.

Correlation between Chemical Characterization and Biological Activity: An Urgent Need for Human Studies Using Extra Virgin Olive Oil.

Extra virgin olive oil (EVOO) is one of the most important functional foods from the Mediterranean Diet due to its beneficial effect on human health in terms of prevention and/or adjuvant treatment of different pathological conditions. The positive effects linked to EVOO consumption are not only due to its major (monounsaturated fatty acids), but also to its minor components (phenolics), whose roles were greatly re-evaluated in the last years. Notwithstanding the huge number of studies demonstrating the antioxidant, anti-inflammatory and anti-cancer properties of EVOO's phenolic compounds, only their antioxidant ability was supported by a Health Claim. However, to bear the claim, a specific phenolic composition is needed, thus reinforcing the need to correlate the characterization of the phenolic compounds to their biological activity. In fact, although the chemical characterization of VOO's phenolic compounds was extensively studied, its correlation with biological effects is only partially investigated; this is especially true for human studies. This review aims to study the correlation between the chemical characterization of EVOO's phenolics and the biological effects in terms of antioxidant/anti-inflammatory potentials, with a focus on the human studies and the relative concern on getting a specific Health Claim.

Genetic, epigenetic and enviromental influencing factors on the regulation of precocious and delayed puberty.

The pubertal development onset is controlled by a network of genes that regulate the gonadotropin releasing hormone (GnRH) pulsatile release and the subsequent increase of the circulating levels of pituitary gonadotropins that activate the gonadal function. Although the transition from pre-pubertal condition to puberty occurs physiologically in a delimited age-range, the inception of pubertal development can be anticipated or delayed due to genetic and epigenetic changes or environmental conditions. Most of the genetic and epigenetic alterations concern genes which encode for kisspeptin, GnRH, LH, FSH and their receptor, which represent crucial factors of the hypothalamic-pituitary-gonadal (HPG) axis. Recent data indicate a central role of the epigenome in the regulation of genes in the hypothalamus and pituitary that could mediate the flexibility of pubertal timing. Identification of epigenetically regulated genes, such as Makorin ring finger 3 (MKRN3) and Delta-like 1 homologue (DLK1), respectively responsible for the repression and the activation of pubertal development, provides additional evidence of how epigenetic variations affect pubertal timing. This review aims to investigate genetic, epigenetic, and environmental factors responsible for the regulation of precocious and delayed puberty.

The Tower of Babel of Pharma-Food Study on Extra Virgin Olive Oil Polyphenols.

Much research has been conducted to reveal the functional properties of extra virgin olive oil polyphenols on human health once EVOO is consumed regularly as part of a balanced diet, as in the Mediterranean lifestyle. Despite the huge variety of research conducted, only one effect of EVOO polyphenols has been formally approved by EFSA as a health claim. This is probably because EFSA's scientific opinion is entrusted to scientific expertise about food and medical sciences, which adopt very different investigative methods and experimental languages, generating a gap in the scientific communication that is essential for the enhancement of the potentially useful effects of EVOO polyphenols on health. Through the model of the Tower of Babel, we propose a challenge for science communication, capable of disrupting the barriers between different scientific areas and building bridges through transparent data analysis from the different investigative methodologies at each stage of health benefits assessment. The goal of this work is the strategic, distinctive, and cost-effective integration of interdisciplinary experiences and technologies into a highly harmonious workflow, organized to build a factual understanding that translates, because of trade, into health benefits for buyers, promoting EVOOs as having certified health benefits, not just as condiments.

Interleukin 1ß Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor-Independent Ulcerative Colitis.

BACKGROUND & AIMS: Inflammatory bowel diseases are multifactorial diseases commonly treated with either immunomodulatory drugs or anti-tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed no earlier than 8-12 weeks after starting treatment) occurs in 20%-40% of patients enrolled in clinical trials and in 10%-20% in clinical practice. Murine models of inflammatory bowel disease provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie-TNF-knockout (KO) mice recently were reported to show characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased interleukin (IL)1ß production. METHODS: Herein, the efficacy of recombinant IL1-receptor antagonist (anakinra) administration was evaluated in Winnie-TNF-KO mice, used as a UC model of primary anti-TNF nonresponders. RESULTS: We analyzed gut mucosal biopsy specimens and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary nonresponders were characterized by abundant IL1ß in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of anakinra efficiently reduced the histologic score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node-derived T cells, interferon γ-expressing CD8+ T cells were reduced significantly after anakinra administration. CONCLUSIONS: Our study provides new insight and alternative approaches to treat UC patients, and points to anti-IL1 strategies (ie, anakinra) that may be a more effective therapeutic option for primary nonresponders to anti-TNF therapy.

Extra virgin olive oil extract rich in secoiridoids induces an anti-inflammatory profile in peripheral blood mononuclear cells from obese children.

Obesity represents an important public health challenge of the twenty first century reaching epidemic proportions worldwide; this is especially true for the pediatric population. In this context, bioactive compounds from foods are crucial to counteract chronic inflammation as a typical feature of obesity. In particular, extra virgin olive oil (EVOO) is one of the most important functional foods exerting, among others, an anti-inflammatory activity not only due to its major (monounsaturated fatty acids) but also to its minor (phenolics) components, as reported in the last years. However, only a limited number of studies were performed on pediatric population, and even fewer are those focusing on EVOO phenolics that investigate the correlation of the chemical characterization with the biological function. Thus, starting from our in vitro data identifying an EVOO chemical profile characterized by a high content of secoiridoids correlating with an anti-inflammatory effect, we studied the ability of an EVOO extract with the same chemical profile to retain this function ex vivo. Specifically, peripheral blood mononuclear cells (PBMCs) collected from obese children were treated with EVOO and olive oil extracts, characterized by a low polyphenol content, to study the ability of secoiridoids to dampen the inflammatory response. A reduction of pro-inflammatory CD14+CD16+ monocytes was detected by cytofluorimetric analysis when PBMCs were treated with EVOO as compared to olive oil extracts. According to this, a down modulation of CCL2 and CCL4 chemokines involved in the recruitment of inflammatory cells, was reported in the supernatants of EVOO relative to olive oil extracts treated PBMCs. Moreover, a high-throughput gene expression analysis revealed that PBMCs molecular profile from obese children is greatly modulated after the treatment with EVOO extract in terms of metabolic and inflammatory pathways. Importantly, some of the significantly modulated genes were involved in the pathways promoting the development of severe obesity. Overall, our ex vivo data demonstrated the ability of EVOO to reduce the inflammatory milieu of PBMCs from obese children both at protein and molecular levels. Of note, a good correlation between the EVOO chemical profile and the biological modulations in terms of anti-inflammatory activity was reported.

Mechanisms of altered bone remodeling in children with type 1 diabetes.

Bone loss associated with type 1 diabetes mellitus (T1DM) begins at the onset of the disease, already in childhood, determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life. The mechanisms underlying diabetic bone fragility are not yet completely understood. Hyperglycemia and insulin deficiency can affect the bone cells functions, as well as the bone marrow fat, thus impairing the bone strength, geometry, and microarchitecture. Several factors, like insulin and growth hormone/insulin-like growth factor 1, can control bone marrow mesenchymal stem cell commitment, and the receptor activator of nuclear factor-κB ligand/osteoprotegerin and Wnt-b catenin pathways can impair bone turnover. Some myokines may have a key role in regulating metabolic control and improving bone mass in T1DM subjects. The aim of this review is to provide an overview of the current knowledge of the mechanisms underlying altered bone remodeling in children affected by T1DM.

Dysbiosis Triggers ACF Development in Genetically Predisposed Subjects.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APCMin/+) combining inflammation and genetics. METHODS: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/+ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother's genetics in ACF development, the large intestines of APCMin/+ mice born from wild type mice were investigated by histological analysis at 8 weeks. RESULTS: ACF development in 8-week-old Winnie-APCMin/+ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/+ hosts leads to an increased rate of ACF development. CONCLUSIONS: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring.

Polyphenol Enriched Diet Administration During Pregnancy and Lactation Prevents Dysbiosis in Ulcerative Colitis Predisposed Littermates.

Neonatal colonization of the gastrointestinal tract depends on mother microbiome, thus mother microbiota dysbiosis is transmitted to the offspring during the delivery and shaped by breastmilk characteristics. Here we used a murine model of UC predisposition (Winnie-/-) to evaluate the effects of maternal diet during pregnancy and lactation. Using heterozygous breeders, we obtained both Winnie-/- and C57BL/6 littermates from the same mother and compared their microbiota at weaning and adult age, using a diet enriched with 1% tomato fruit of a line - named Bronze - highly enriched in bioactive polyphenols, or Control tomato. Females received enriched diets two weeks before the beginning of the breeding and never stopped for the following six months. No significant effect was observed in regard to the percentage of Winnie-/- offspring, as with both diets the percentage was about 25% as expected. Winnie littermates from breeders fed with the Bronze-enriched diet showed reduced dysbiosis at 4 weeks of age if compared with Winnie under the Control tomato diet. This effect was then reduced when mice reached adult age. Conversely, the microbiota of C57BL/6 does not change significantly, indicating that fortified mothers-diet significantly contribute to preventing dysbiosis in genetically predisposed offspring, but has mild effects on healthy littermates and adult mice. An overall tendency towards reduced inflammation was underlined by the colon weight and the percentage of Foxp3+ cells reduction in Winnie mice fed with Bronze diet. Control diet did not show similar tendency.

Uridine and pyruvate protect T cells' proliferative capacity from mitochondrial toxic antibiotics: a clinical pilot study.

Antibiotics that inhibit bacterial protein or nucleic acid synthesis and function can exert an off-target action on mitochondria (mitotoxic antibiotics), making actively dividing mammalian cells dependent on uridine and pyruvate supplementation. Based on this rationale, we carried out, for the first time, a randomized pilot study in 55 patients with asymptomatic bacteriuria or positive sperm culture, each treated with a single mitotoxic antibiotic with or without oral supplementation of uridine + pyruvate (Uripyr, Mitobiotix, Italy). The in vivo and ex vivo data show a a 3.4-fold higher value in the differential (before and after the antibiotic treatment) lymphocytes count and a 3.7-fold increase in the percentage of dividing T cells, respectively, in the Uripyr vs the control group. Our findings lay the groundwork to enhance the synergy between antibiotics and the immune system in order to optimize the administration protocols and widen the application potentials of antibiotic therapies as well as to re-evaluate old "forgotten" molecules to fight bacterial infections in the antibiotics resistance era.

Extra Virgin Olive Oil Extracts Modulate the Inflammatory Ability of Murine Dendritic Cells Based on Their Polyphenols Pattern: Correlation between Chemical Composition and Biological Function.

Extra virgin olive oil (EVOO) represents one of the most important health-promoting foods whose antioxidant and anti-inflammatory activities are mainly associated to its polyphenols content. To date, studies exploring the effect of EVOO polyphenols on dendritic cells (DCs), acting as a crosstalk between the innate and the adaptive immune response, are scanty. Therefore, we studied the ability of three EVOO extracts (cv. Coratina, Cima di Mola/Coratina, and Casaliva), characterized by different polyphenols amount, to regulate DCs maturation in resting conditions or after an inflammatory stimulus. Cima di Mola/Coratina and Casaliva extracts were demonstrated to be the most effective in modulating DCs toward an anti-inflammatory profile by reduction of TNF and IL-6 secretion and CD86 expression, along with a down-modulation of Il-1ß and iNOS expression. From factorial analysis results, 9 polyphenols were tentatively established to play a synergistic role in modulating DCs inflammatory ability, thus reducing the risk of chronic inflammation.