Oral Supplementation With Selected Lactobacillus Acidophilus Triggers Antimicrobial Response, Activation of Innate Lymphoid Cells Type 3 And Improves Colitis

2021 ◽  
Author(s):  
Jiří Hrdý ◽  
Aurélie Couturier-Maillard ◽  
Denise Boutillier ◽  
Carmen Lapadatescu ◽  
Philippe Blanc ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Lactobacillus Acidophilus ◽  
Target Genes ◽  
Intestinal Inflammation ◽  
Probiotic Strain ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Trinitrobenzene Sulfonic Acid ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that are illustrated by direct and indirect antimicrobial activity against several pathogens and improvement of intestinal inflammation. In this study, we evaluated the anti-inflammatory properties of the L. acidophilus strain BIO5768 and assessed the underlying mechanisms of action. BIO5768 was able to counteract the acute colitis that is induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was also able to alleviate intestinal inflammation induced by Citrobacter rodentium infection. Supplementation of naïve mice with either strain BIO5768 alone or as mixture, increased the gene expression of several target genes involved in immune signaling, including c-type lectin Reg3 gamma. Consistently, the ability of innate lymphoid cells to secrete IL-22 was enhanced in response to BIO5768. Interestingly, the aforementioned responses were shown to be independent of NOD2 and Th17 signaling in mice that were mono-colonized with BIO5768. In conclusion, we identify a new potential probiotic strain with the ability for the management of inflammatory bowel diseases, and provide some insights into its mode of action.

scholarly journals Innate Lymphoid Cells as Regulators of Epithelial Integrity: Therapeutic Implications for Inflammatory Bowel Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Anja Schulz-Kuhnt ◽  
Markus F. Neurath ◽  
Stefan Wirtz ◽  
Imke Atreya
Keyword(s):  
Epithelial Cell ◽  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Innate Lymphoid Cells ◽  
Experimental Models ◽  
Lymphoid Cells ◽  
Intestinal Epithelial ◽  
Epithelial Integrity ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The occurrence of epithelial defects in the gut relevantly contributes to the pathogenesis of inflammatory bowel diseases (IBD), whereby the impairment of intestinal epithelial barrier integrity seems to represent a primary trigger as well as a disease amplifying consequence of the chronic inflammatory process. Besides epithelial cell intrinsic factors, accumulated and overwhelmingly activated immune cells and their secretome have been identified as critical modulators of the pathologically altered intestinal epithelial cell (IEC) function in IBD. In this context, over the last 10 years increasing levels of attention have been paid to the group of innate lymphoid cells (ILCs). This is in particular due to a preferential location of these rather newly described innate immune cells in close proximity to mucosal barriers, their profound capacity to secrete effector cytokines and their numerical and functional alteration under chronic inflammatory conditions. Aiming on a comprehensive and updated summary of our current understanding of the bidirectional mucosal crosstalk between ILCs and IECs, this review article will in particular focus on the potential capacity of gut infiltrating type-1, type-2, and type-3 helper ILCs (ILC1s, ILC2s, and ILC3s, respectively) to impact on the survival, differentiation, and barrier function of IECs. Based on data acquired in IBD patients or in experimental models of colitis, we will discuss whether the different ILC subgroups could serve as potential therapeutic targets for maintenance of epithelial integrity and/or mucosal healing in IBD.

Innate lymphoid cells in inflammatory bowel diseases

2016 ◽  
Vol 172 ◽  
pp. 124-131 ◽  
Author(s):  
C.P. Peters ◽  
J.M. Mjösberg ◽  
J.H. Bernink ◽  
H. Spits
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Genetic and Pharmacological Dissection of the Role of Spleen Tyrosine Kinase (Syk) in Intestinal Inflammation and Immune Dysfunction in Inflammatory Bowel Diseases

2017 ◽  
Vol 24 (1) ◽  
pp. 123-135 ◽  
Author(s):  
Michele Biagioli ◽  
Andrea Mencarelli ◽  
Adriana Carino ◽  
Sabrina Cipriani ◽  
Silvia Marchianò ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Adaptor Protein ◽  
Immune Dysfunction ◽  
Trinitrobenzene Sulfonic Acid ◽  
Spleen Tyrosine Kinase ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background The DNAX adaptor protein 12 (DAP12) is a transmembrane adaptor molecule that signals through the activation of Syk (Spleen Tyrosine Kinase) in myeloid cells. The purpose of this study is to investigate the role of DAP12 and Syk pathways in inflammatory bowel diseases (IBDs). Methods DAP12 deficient and DAP12 transgenic, overexpressing an increased amount of DAP12, mice and Syk deficient mice in the C57/BL6 background were used for these studies. Colitis was induced by administering mice with dextran sulfate sodium (DSS), in drinking water, or 2,4,6-trinitrobenzene sulfonic acid (TNBS), by intrarectal enema. Results Abundant expression of DAP12 and Syk was detected in colon samples obtained from Crohn’s disease patients with expression restricted to immune cells infiltrating the colonic wall. In rodents development of DSS colitis as measured by assessing severity of wasting diseases, global colitis score,and macroscopic and histology scores was robustly attenuated in DAP12-/- and Syk-/- mice. In contrast, DAP12 overexpression resulted in a striking exacerbation of colon damage caused by DSS. Induction of colon expression of proinflammatory cytokines and chemokines in response to DSS administration was attenuated in DAP12-/- and Syk-/- mice, whereas opposite results were observed in DAP12 transgenic mice. Treating wild-type mice with a DAP-12 inhibitor or a Syk inhibitor caused a robust attenuation of colitis induced by DSS and TNBS. Conclusions DAP12 and Syk are essential mediators in inflammation-driven immune dysfunction in murine colitides. Because DAP12 and Syk expression is upregulated in patients with active disease, present findings suggest a beneficial role for DAP12 and Syk inhibitors in IBD.

scholarly journals Imaging in Inflammatory Bowel Diseases - Magnetic Resonance Imaging

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 26-31
Author(s):  
Hans Herfarth ◽  
Andreas G. Schreyer
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Magnetization Transfer ◽  
Diagnostic Value ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Line Imaging ◽  
Sensitivity Specificity

Diagnostic imaging techniques play an important role in the diagnosis and management of patients with inflammatory bowel diseases (IBDs). The approach should be guided by considerations of diagnostic accuracy, concerns about patient exposure to ionizing radiation, local expertise and tolerance of the endoscopic and/or imaging technique. In regard to the clinical diagnostic value (sensitivity, specificity and accuracy), no significant differences exist between CT and MRI for the evaluation of the extent of inflammation, stricturing, penetrating disease or extraluminal complications such as abscesses. Due to the absence of radiation exposure, MRI of the intestine is recommended as the first-line imaging modality in patients with suspected or established IBD. The focus of this review is the latest developments in MRI techniques to detect IBDs. Specifically, the use of new indices for the grading of inflammation or assessing bowel damage as well as innovative experimental approaches such as diffusion-weighted imaging or magnetization-transfer MRI to evaluate and quantify the degree of intestinal inflammation and fibrosis in stricturing Crohn's disease are discussed.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

scholarly journals A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut

2019 ◽  
Vol 4 (40) ◽  
pp. eaax1215 ◽  
Author(s):  
Fei Teng ◽  
Jeremy Goc ◽  
Lei Zhou ◽  
Coco Chu ◽  
Manish A. Shah ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Target Genes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Expression Of Genes ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Group 3 ◽  
Host Microbe Interactions ◽  
Specific Deletion

Group 3 innate lymphoid cells (ILC3s) critically orchestrate host-microbe interactions in the healthy mammalian intestine and become substantially impaired in the context of inflammatory bowel disease (IBD). However, the molecular pathways controlling the homeostasis of ILC3s remain incompletely defined. Here, we identify that intestinal ILC3s are highly enriched in expression of genes involved in the circadian clock and exhibit diurnal oscillations of these pathways in response to light cues. Classical ILC3 effector functions also exhibited diurnal oscillations, and lineage-specific deletion of BMAL1, a master regulator of the circadian clock, resulted in markedly reduced ILC3s selectively in the intestine. BMAL1-deficient ILC3s exhibit impaired expression of Nr1d1 and Per3, hyperactivation of RORγt-dependent target genes, and elevated proapoptotic pathways. Depletion of the microbiota with antibiotics partially reduced the hyperactivation of BMAL1-deficient ILC3s and restored cellular homeostasis in the intestine. Last, ILC3s isolated from the inflamed intestine of patients with IBD exhibit substantial alterations in expression of several circadian-related genes. Our results collectively define that circadian regulation is essential for the homeostasis of ILC3s in the presence of a complex intestinal microbiota and that this pathway is disrupted in the context of IBD.

Protective effects of a novel probiotic strain, Lactococcus lactis ML2018, in colitis: in vivo and in vitro evidence

2019 ◽  
Vol 10 (2) ◽  
pp. 1132-1145 ◽  
Author(s):  
Meiling Liu ◽  
Xiuxia Zhang ◽  
Yunpeng Hao ◽  
Jinhua Ding ◽  
Jing Shen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lactococcus Lactis ◽  
Intestinal Microbiota ◽  
Inflammatory Bowel Diseases ◽  
Probiotic Strain ◽  
Protective Effects ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Multiple articles have confirmed that an imbalance of the intestinal microbiota is closely related to aberrant immune responses of the intestines and to the pathogenesis of inflammatory bowel diseases (IBDs).

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