Effect of Yoghurt on the Cytokine Profile using a Murine Model of Intestinal Inflammation

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are important problems in industrialized countries. The complete aetiology of both diseases is still unknown but likely involves genetic, environmental and immunological factors. The aim of this work is to study the anti-inflammatory mechanisms reported for yoghurt in a colon cancer model in order to evaluate its usefulness in the treatment of intestinal inflammation such as Crohn's disease. A trinitrobenzenesulfonic acid (TNBS)-induced colitis model was used. The influence of yoghurt feeding was studied before and after TNBS inoculation. The effect on the intestinal microbiota and on the host immune response was evaluated. IgA-producing cells and cells positive for specific cytokines (IL-12, IL-17, IFNγ and IL-10) were analyzed. Yoghurt administration diminished the severity of inflammation in the TNBS-inoculated mice. This effect occurred mainly through IL-10, which was increased in the intestinal tissues throughout the study, and by the decrease observed in IL-17 and IL-12 levels. In addition to this immunomodulatory capacity, another mechanism by which yoghurt could exert the anti-inflammatory activity observed in our model would be through beneficial changes in the intestinal microbiota (increases in the bifidobacteria and lactobacilli populations). These changes in the intestinal microbiota could also be considered one of the causes of the intestinal inflammation reduction. These results show that yoghurt administration modulated the immune response, inducing down regulation of the inflammatory cytokines produced by the immune cells involved in the inflammatory process. The protective effect

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Evaluation of changes in intestinal microbiota in Crohn’s disease patients after anti-TNF alpha treatment

Scientific Reports ◽

10.1038/s41598-021-88823-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Laura Sanchis-Artero ◽

Juan Francisco Martínez-Blanch ◽

Sergio Manresa-Vera ◽

Ernesto Cortés-Castell ◽

Marina Valls-Gandia ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota ◽

Area Under The Curve ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Fecal Microbiota ◽

Multicenter Observational Study ◽

Partial Restoration ◽

Before And After

AbstractIntestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

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Enteral nutrition for pediatric Crohn’s disease: significance and basic principles

Voprosy detskoj dietologii ◽

10.20953/1727-5784-2021-3-70-82 ◽

2021 ◽

Vol 19 (3) ◽

pp. 70-82

Author(s):

T.E.Borovik T.E.Borovik ◽

◽

A.S.Potapov A.S.Potapov ◽

E.A.Roslavtseva E.A.Roslavtseva ◽

A.I.Khavkin A.I.Khavkin ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Nutritional Support ◽

Intestinal Inflammation ◽

Bone Mineralization ◽

Standard Diet ◽

Newly Diagnosed ◽

Basic Principles ◽

Inflammatory Bowel

The characteristics of the diet traditionally recommended for Crohn’s disease often reduce patients’ consumption of essential nutrients. Therefore, an important role belongs to nutritional support with specialized formulas, the effectiveness of which has been proven both for inducing remission and optimizing the parameters of physical development and puberty, bone mineralization. Nutritional support should be provided for patients with newly diagnosed Crohn’s disease in the form of full enteral nutrition, and subsequently in remission, exacerbation, in the pre- and postoperative periods as an addition to the standard diet. Of particular interest is the CDED ModuLife program, which is based on a combination of enteral nutrition with specially selected foods aimed at reducing the activity of intestinal inflammation in Crohn’s disease. Key words: inflammatory bowel disease, Crohn’s disease, full enteral nutrition, partial enteral nutrition, enteral nutrition formulas

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Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00423.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. G169-G174 ◽

Cited By ~ 56

Author(s):

Gert Van Assche ◽

Paul Rutgeerts

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adhesion Molecules ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Therapeutic Potential ◽

Physiological Basis ◽

Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

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Fecal microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease Patients with Irritable Bowel Syndrome-Type Symptoms

10.21203/rs.3.rs-152044/v1 ◽

2021 ◽

Author(s):

Xiufang Cui ◽

Haiyang Wang ◽

Ziping Ye ◽

Yi Li ◽

Xinyun Qiu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Irritable Bowel Syndrome ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Sectional Study ◽

Genus Level ◽

Inflammatory Bowel ◽

Irritable Bowel

Abstract BACKGROUND: The intestinal microbiota is thought to be involved in the occurrence of Inflammatory Bowel Disease in remission (IBDR) with Irritable Bowel Syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. Therefore, the purpose of this research is to investigate this issue by conducting a cross-sectional study.METHODS: IBS patients were diagnosed according to Rome Ⅳ criteria, IBD diagnosed according to the criteria of European Crohn & Colitis Organization (ECCO), IBDR patients with IBS-type symptoms were defined according to related IBS-type symptoms meeting the Rome IV criteria in IBDR patients, and were included Crohn’s disease in remission (CDR) and ulcerative colitis in remission (UCR) based on Crohn’s Disease Activity Index (DAI) and Mayo Scoring System respectively. Healthy controls come from the physical examination center and exclude people with underlying diseases. All enrolled subjects were divided into six groups, as followed: Health Control, IBS, CDR with IBS-type symptoms (CDR-IBS+), CDR without IBS-type symptoms (CDR-IBS-), UCR-IBS+ and UCR-IBS-. We collected fresh fecal samples from all subjects and applied 16S rRNA sequencing analysis to detect the structure and diversity of the microbiota among different groups. RESULTS: A total of 97 subjects were included in this study, of which 18 were health controls, 34 IBS patients, 25 CDR and 20 UCR. The richness of intestinal microbiota in CDR-IBS-was significantly lower than that in the control and IBS groups based on the analysis of observed species and Chao index (P<0.05). The observed species index in CDR-IBS+ was significantly higher than CDR-IBS- group (median index: 254.8 vs 203, P=0.036). No difference was found in Alpha diversity between UCR-IBS+ and UCR-IBS-. At phylum level, there was no significant difference between UC or CD with IBS-type symptoms and those without related symptoms. At genus level, the number of Faecalibacterium in CDR-IBS+ increased significantly while Fusobacterium decreased compared with CDR-IBS-(mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P<0.05; Fusobacterium: 1.51% vs 5.2%, P<0.05). However, compared with UCR-IBS - group, the number of Faecalibacterium in UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no statistical difference in the genus structure. Regardless of the phylum or genus level, the abundance and composition of the microbiota of IBS patients were not distinct from those of healthy people.CONCLUSIONS: CD patients in remission with IBS-type symptoms may be related to the increase of Faecalibacterium and decrease of Fusobacterium. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.

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Immune system alterations in patients with inflammatory bowel disease during remission

Medicina ◽

10.3390/medicina44010005 ◽

2008 ◽

Vol 44 (1) ◽

pp. 27 ◽

Cited By ~ 14

Author(s):

Jurgita Šventoraitytė ◽

Aida Žvirblienė ◽

Gediminas Kiudelis ◽

Rimantas Žalinkevičius ◽

Aurelija Žvirblienė ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Immune Homeostasis ◽

Th2 Cytokines ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

And Control

Objective. Perturbed immune homeostasis elicited by misbalanced production of proinflammatory and anti-inflammatory cytokines is characteristic of inflammatory bowel disease. The aim of this study was to evaluate cytokine profile in patients with different forms of inflammatory bowel disease – ulcerative colitis and Crohn’s disease – during clinical remission phase. Material and methods. Production of proinflammatory Th1 cytokines (tumor necrosis factoralpha (TNF-a), interferon-gamma (IFN-g)) and anti-inflammatory Th2 cytokines (interleukin- 10 (IL-10) and interleukin-13 (IL-13)) was analyzed in peripheral blood mononuclear cells of patients with inflammatory bowel disease (9 with ulcerative colitis and 9 with Crohn’s disease) and control subjects (n=11) by enzyme-linked immunosorbent assay (two-site ELISA). Results. The results of the study revealed that the level of TNF-a after stimulation with phytohemagglutinin in patients with Crohn’s disease was significantly higher in comparison to both patients with ulcerative colitis and controls (P<0.001 and P<0.01, respectively). The secretion of IFN-g both in patients with Crohn’s disease and ulcerative colitis was lower than that in controls (P=0.05 and P<0.01, respectively), but it normalized after stimulation with phytohemagglutinin. The levels of IL-10 and IL-13 were significantly (P<0.01) higher in patients with Crohn’s disease than in patients with ulcerative colitis and control group before and after stimulation with phytohemagglutinin. Conclusions. The results of our study provide evidence that in patients with inflammatory bowel disease, the imbalance between production of proinflammatory Th1 and anti-inflammatory Th2 cytokines persists even during remission of the disease, and disturbances of immune homeostasis are significantly more expressed in patients with Crohn’s disease than in patients with ulcerative colitis.

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The association between inflammatory potential of diet and disease activity: results from a cross-sectional study in patients with inflammatory bowel disease

BMC Gastroenterology ◽

10.1186/s12876-020-01435-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Carlijn R. Lamers ◽

Nicole M. de Roos ◽

Ben J. M. Witteman

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Statistical Significance ◽

Inflammatory Bowel ◽

Anti Inflammatory

Abstract Background Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn’s disease and ulcerative colitis. Methods Participants completed a disease activity questionnaire (short Crohn’s Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals’ diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. Results The analysis included 329 participants; 168 with Crohn’s disease (median sCDAI score 93 [IQR 47–156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1–3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn’s disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. Conclusions Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn’s disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.

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Comorbid Inflammatory Diseases of Digestive System and Eye

Ophthalmology in Russia ◽

10.18008/1816-5095-2021-1-20-29 ◽

2021 ◽

Vol 18 (1) ◽

pp. 20-29

Author(s):

S. A. Bulgakov ◽

G. M. Chernakova ◽

E. A. Kleshcheva ◽

S. V. Simonova

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Ophthalmological Examination ◽

Extraintestinal Manifestations ◽

Bowel Diseases ◽

Inflammatory Bowel

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases, which are often accompanied by inflammation of other organs. This article presents modern data on etiology, pathogenesis and clinical course of inflammatory bowel diseases, as well as information on extraintestinal eye manifestations of nonspecific ulcerative colitis and Crohn’s disease. The role of microbiota, genetic factors, immune system defects in pathogenesis of intestinal inflammation and extraintestinal eye manifestations is considered. The possibility the development of ophthalmopathology not only against the background of intestinal inflammation, but also as a consequence of therapeutic and surgical methods of treatment of ulcerative colitis and Crohn’s disease is noted. The peculiarities of the course of episcleritis/scleritis, keratitis, uveitis, chorioretinitis, optical neuritis for patients with inflammatory bowel diseases are considered. The presence of these complications may reflect the activity of the underlying disease, which in some cases requires correction of therapy. Anterior uveitis and episcleritis/scleritis are the most common extraintestinal manifestations of inflammatory bowel disease. Inflammation of tissues of the posterior segment of the eye and optic nerve against the background of ulcerative colitis and Crohn’s disease are less common, but are of clinical importance, as they can catastrophically damage the structures of the eye and, as a consequence, lead to complete blindness. Considering the possibility of mild clinical symptoms and asymptomatic course of inflammation in the eye envelopes, the importance of ophthalmological examination of all patients with ulcerative colitis and Crohn’s disease is emphasized. Aspects of modern therapy of ophthalmopathology and background intestinal inflammation are highlighted. Biological preparations — antagonists of pro-inflammatory cytokines — have been identified as the most promising in the treatment of inflammatory intestinal diseases and extraintestinal manifestations. The important role of proper nutrition and biologically active supplements containing omega-3 fatty acids, vitamin D, microelements, was noted as auxiliary therapy of both intestinal and extraintestinal inflammation.

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Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights

Cells ◽

10.3390/cells8060577 ◽

2019 ◽

Vol 8 (6) ◽

pp. 577 ◽

Cited By ~ 2

Author(s):

Benoît Foligné ◽

Coline Plé ◽

Marie Titécat ◽

Arnaud Dendooven ◽

Aurélien Pagny ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Trinitrobenzene Sulfonic Acid ◽

T Helper ◽

Anti Inflammatory ◽

Transplantation Experiments

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn’s disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn’s disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.

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Mo1782 Presence of Genotypes of Bacteroidetes Associated With Intestinal Microbiota in Patients With Crohn's Disease and Evaluation of Its Role in the Induction of Intestinal Inflammation in Mice

Gastroenterology ◽

10.1016/s0016-5085(15)32412-4 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-710

Author(s):

Manuel Barreiro-de Acosta ◽

Rosana Sueiro ◽

Ana Paula De Felipe ◽

Laura Uribarri-González ◽

Rocio Ferreiro ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota ◽

Intestinal Inflammation

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Probiotics and bowel inflammation

Arbor Clinical Nutrition Updates ◽

10.1017/s1446545000000610 ◽

2006 ◽

Vol 247 ◽

pp. 1-4

Keyword(s):

Ulcerative Colitis ◽

Immune Response ◽

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Inflammatory Bowel Diseases ◽

Safety Issues ◽

Bowel Diseases ◽

Inflammatory Bowel

In a nutshellInflammatory bowel diseases can involve problems in the development of the gut's immune response. A healthy bowel flora plays an important role in this development, for example through effects on cytokines.Clinical trials of probiotics for IBD have been predominantly positive for ulcerative colitis and pouchitis, less so for Crohn's disease. So far probiotics appear to be a notably safe therapy, although some theoretical safety issues need to be borne in mind.

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