scholarly journals Intestinal Microbial Metabolites in Ankylosing Spondylitis

2021 ◽  
Vol 10 (15) ◽  
pp. 3354
Author(s):  
Giuseppe Scalise ◽  
Antonio Ciancio ◽  
Daniele Mauro ◽  
Francesco Ciccia
Keyword(s):  
Immune System ◽  
Ankylosing Spondylitis ◽  
Short Chain Fatty Acids ◽  
Chronic Inflammatory Disease ◽  
Host Cells ◽  
Intestinal Lumen ◽  
Dietary Interventions ◽  
Pharmacological Targets ◽  
Triggering Factor ◽  
Type 3

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammation of axial joints and the pelvis. It is known that intestinal dysbiosis may exert direct pathogenic effects on gut homeostasis and may act as a triggering factor for the host innate immune system to activate and cause inflammation in extraintestinal sites in the so-called “gut-joint axis”, contributing to AS pathogenesis. However, although the intestinal microbiota’s influence on the clinical manifestation of AS is widely accepted, the mechanisms mediating the cross-talk between the intestinal lumen and the immune system are still not completely defined. Recent evidence suggests that the metabolism of microbial species may be a source of metabolites and small molecules participating in the complex network existing between bacteria and host cells. These findings may give inputs for further research of novel pharmacological targets and pave the way to applying dietary interventions to prevent the onset and ameliorate the clinical presentation of the disease. In this review, we discuss the role of some of the biological mediators of microbial origin, with a particular focus on short-chain fatty acids, tryptophan and vitamin B derivatives, and their role in barrier integrity and type 3 immunity in the context of AS.

The effect of diet on hypertensive pathology: is there a link via gut microbiota-driven immunometabolism?

2019 ◽  
Vol 115 (9) ◽  
pp. 1435-1447 ◽  
Author(s):  
Hamdi A Jama ◽  
Anna Beale ◽  
Waled A Shihata ◽  
Francine Z Marques
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Experimental Hypertension ◽  
Dietary Interventions ◽  
The Past ◽  
Sequence Of Events ◽  
Clinical Hypertension ◽  
Protein Receptors ◽  
Small And Large Intestine

Abstract Over the past decade, the immune system has emerged as an important component in the aetiology of hypertension. There has been a blooming interest in the contribution of the gut microbiota, the microbes that inhabit our small and large intestine, to blood pressure (BP) regulation. The gastrointestinal tract houses the largest number of immune cells in our body, thus, it is no surprise that its microbiota plays an important functional role in the appropriate development of the immune system through a co-ordinated sequence of events leading to immune tolerance of commensal bacteria. Importantly, recent evidence supports that the gut microbiota can protect or promote the development of experimental hypertension and is likely to have a role in human hypertension. One of the major modulators of the gut microbiota is diet: diets that emphasize high intake of fermentable fibre, such as the Mediterranean diet and the Dietary Approaches to Stop Hypertension, promote expansion of protective microbes that release gut metabolites such as short-chain fatty acids, which are immune-, BP-, and cardio-protective, likely acting through G-coupled protein receptors. In contrast, diets lacking fibre or high in salt and fat, such as the Western diet, reduce prevalence of commensal microbial species and support a pathogenic and pro-inflammatory environment, including the release of the pro-atherosclerotic trimethylamine N-oxide. Here, we review the current understanding of the gut microbiota-driven immune dysfunction in both experimental and clinical hypertension, and how these changes may be addressed through dietary interventions.

scholarly journals Microbiota-derived metabolites, short chain-fatty acids, induce epigenetic modifications in CD4+ T cells in mice

2019 ◽  
Author(s):  
Raissa Carolina Alves da Silva ◽  
Marco Aurelio Ramirez Vinolo ◽  
Laís Passarielo Pral ◽  
José Luis Fachi
Keyword(s):  
Fatty Acids ◽  
T Cells ◽  
Regulatory T Cells ◽  
Short Chain Fatty Acids ◽  
Host Cells ◽  
Short Chain ◽  
Intestinal Lumen ◽  
Host Interaction ◽  
Key Aspects ◽  
Chain Fatty Acids

The gut microbiota is indispensable for the host, considering its role in regulating key aspects of host homeostasis, such as development, function and induction of T cells. One of the possibilities for microbiota-host interaction is through short-chain fatty acids (SCFAs). compounds produced by fermentation of dietary fiber of intestinal lumen bacteria. These compounds can regulate gene expression, by promoting inhibition of histone deacetylase enzimes (HDACs) and activation of histone acetyltransferases enzimes (HATs), thus increasing post-translational modifications such as acetylation and crotonylation. However, details of how these two types of modifications act on host cells, especially regulatory T cells, remains to be seen. Therefore, our aim was to evaluate the SCFA mediated role of microbiota on acetylation and crotonylation of regulatory T cells, as to verify how these two modifications can interact in the histone modification scenario. In conclusion, acetylation and crotonylation, linked to microbiota, have the potential to form an importante part in regulation of T CD4+ cells and can interact and modify directly the action of HDAC enzimes, which is notably relevant to microbiota-host interface.

scholarly journals Transmission Electron Microscopic Demonstration of Phagocytosis and Intracellular Processing of Segmented Filamentous Bacteria by Intestinal Epithelial Cells of the Chick Ileum

2000 ◽  
Vol 68 (11) ◽  
pp. 6496-6504 ◽  
Author(s):  
Koh-En Yamauchi ◽  
Johannes Snel
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Mucosal Immune System ◽  
Host Cells ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Filamentous Bacteria ◽  
Segmented Filamentous Bacteria ◽  
Transmission Electron

ABSTRACT Segmented filamentous bacteria (SFB) are autochthonous bacteria colonizing the ileum of many young animals by attaching to intestinal epithelial cells. These nonpathogenic bacteria strongly stimulate the mucosal immune system and induce intestinal epithelial cells to express major histocompatibility complex class II molecules. We tried to discover whether SFB are phagocytized and intracellularly processed by the host cells, which is indicative of antigen processing. The middle part of the ileum was extracted from 10- and 20-day-old broiler chicks (Gallus gallus domesticus). Samples were processed and examined by scanning and transmission electron microscopy (SEM and TEM, respectively). In SEM, no, few, medium, and dense SFB colonization levels were classified. In TEM of cells from animals with medium or dense SFB colonization levels, we could observe extracellular particles ranging from those only indenting the cell membrane to particles found in the cytoplasmatic area beyond the terminal web. These particles had a structural similarity with SFB that were floating freely in the intestinal lumen. Furthermore, we observed unlacing of the membrane and septum surrounding the extracellular particles and their incorporation into host cytoplasmatic components, which strongly suggests that these particles are phagocytized and intracellularly processed SFB. This conclusion is supported by TEM analysis of samples with no or few SFB, in which we failed to find these characteristic morphologies. The phagocytosis process described here could be an important trigger for the stimulating effect of SFB on the mucosal immune system.

scholarly journals Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?

2021 ◽  
Vol 11 ◽  
Author(s):  
Katja Schlatterer ◽  
Andreas Peschel ◽  
Dorothee Kretschmer
Keyword(s):  
Immune System ◽  
Influenza Viruses ◽  
Host Cells ◽  
Short Chain ◽  
Intestinal Microbiome ◽  
Intestinal Lumen ◽  
Klebsiella Pneumonia ◽  
Skin Microbiome ◽  
Acetate Production ◽  
Food Ingredients

The human innate immune system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. The metabolite short-chain fatty acids (SCFAs) acetate, propionate and butyrate are released by multiple bacteria or are food ingredients. SCFA production, especially acetate production, is usually essential for bacteria, and knockout of pathways involved in acetate production strongly impairs bacterial fitness. Because host organisms use SCFAs as MAMPs and alter immune reactions in response to SCFAs, interventions that modulate SCFA levels can be a new strategy for infection control. The interaction between SCFAs and host cells has been primarily investigated in the intestinal lumen because of the high local levels of SCFAs released by bacterial microbiome members. However, members of not only the intestinal microbiome but also the skin microbiome produce SCFAs, which are known ligands of the seven-transmembrane G-protein-coupled receptor FFAR2. In addition to enterocytes, FFAR2 is expressed on other human cell types, including leukocytes, especially neutrophils. This finding is in line with other research that determined that targeted activation of FFAR2 diminishes susceptibility toward various types of infection by bacteria such as Klebsiella pneumonia, Citrobacter rodentium, and Staphylococcus aureus but also by viruses such as respiratory syncytial and influenza viruses. Thus, our immune system appears to be able to use FFAR2-dependent detection of SCFAs for perceiving and even averting severe infections. We summarize recent advances in understanding the role of SCFAs and FFAR2 in various infection types and propose the manipulation of this receptor as an additional therapeutic strategy to fight infections.

Gastrointestinal Interaction between Dietary Amino Acids and Gut Microbiota: With Special Emphasis on Host Nutrition

2020 ◽  
Vol 21 (8) ◽  
pp. 785-798 ◽  
Author(s):  
Abedin Abdallah ◽  
Evera Elemba ◽  
Qingzhen Zhong ◽  
Zewei Sun
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Immune System ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Nutrition And Health ◽  
Nitrogenous Compounds ◽  
Dietary Amino Acids ◽  
Host Nutrition ◽  
Chain Fatty Acids

The gastrointestinal tract (GIT) of humans and animals is host to a complex community of different microorganisms whose activities significantly influence host nutrition and health through enhanced metabolic capabilities, protection against pathogens, and regulation of the gastrointestinal development and immune system. New molecular technologies and concepts have revealed distinct interactions between the gut microbiota and dietary amino acids (AAs) especially in relation to AA metabolism and utilization in resident bacteria in the digestive tract, and these interactions may play significant roles in host nutrition and health as well as the efficiency of dietary AA supplementation. After the protein is digested and AAs and peptides are absorbed in the small intestine, significant levels of endogenous and exogenous nitrogenous compounds enter the large intestine through the ileocaecal junction. Once they move in the colonic lumen, these compounds are not markedly absorbed by the large intestinal mucosa, but undergo intense proteolysis by colonic microbiota leading to the release of peptides and AAs and result in the production of numerous bacterial metabolites such as ammonia, amines, short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), hydrogen sulfide, organic acids, and phenols. These metabolites influence various signaling pathways in epithelial cells, regulate the mucosal immune system in the host, and modulate gene expression of bacteria which results in the synthesis of enzymes associated with AA metabolism. This review aims to summarize the current literature relating to how the interactions between dietary amino acids and gut microbiota may promote host nutrition and health.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals TYPE III CAWLEY ANDERSSON LESION IN A CASE OF ANKYLOSING SPONDYLITIS

2014 ◽  
Vol 04 (02) ◽  
pp. 136-139
Author(s):  
Deepak Hegde ◽  
Ballal Arjun ◽  
Vinay Kumar C. ◽  
H. Ravindranath Rai
Keyword(s):  
Back Pain ◽  
Ankylosing Spondylitis ◽  
Morning Stiffness ◽  
Posterior Spinal Fusion ◽  
Chronic Inflammatory Disease ◽  
Inflammatory Back Pain ◽  
Type Iii ◽  
Lesion Type ◽  
Andersson Lesion ◽  
Spinal Ligament

Abstract:Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects especially males in the second and third decades of life.1 The main clinical symptom is inflammatory back pain typically occurring at night and morning stiffness improving after exercise.1 Apart from syndesmophytes and ankylosis of the spine resulting in rigidity, in longstanding ankylosing spondylitis, also focal destructive 1 discovertebral lesions (Andersson lesions) can occur.1 The case we present here is of a 35 year old male patient who presented to us with the symptoms of pain of upper back and both shoulders for 6 years. Pain was followed with stiffness of the neck and shoulder. Radiography of the dorsolumbar spine revealed squaring of the vertebra, syndesmophytes, calcification of the anterior spinal ligament, end plate irregularity at D10-D11 level, ill defined sclerosis with fracture of the ankylosed spine, features consistent with Andersson lesion type III. He underwent posterior spinal fusion with good functional outcome.

scholarly journals Dietary supplementation with Bifidobacterium lactis NCC2818 from weaning reduces local immunoglobulin production in lymphoid-associated tissues but increases systemic antibodies in healthy neonates

2013 ◽  
Vol 110 (7) ◽  
pp. 1243-1252 ◽  
Author(s):  
Marie C. Lewis ◽  
Dilip V. Patel ◽  
Jenni Fowler ◽  
Swantje Duncker ◽  
Adrian W. Zuercher ◽  
...  
Keyword(s):  
Immune System ◽  
Health Benefit ◽  
Dietary Supplementation ◽  
Nutritional Intervention ◽  
Dietary Interventions ◽  
Probiotic Supplementation ◽  
Human Infants ◽  
Bifidobacterium Lactis ◽  
Beneficial Effects ◽  
Mucosal Tissues

Weaning is associated with a major shift in the microbial community of the intestine, and this instability may make it more acquiescent than the adult microbiota to long-term changes. Modulation achieved through dietary interventions may have potentially beneficial effects on the developing immune system, which is driven primarily by the microbiota. The specific aim of the present study was to determine whether immune development could be modified by dietary supplementation with the human probiotic Bifidobacterium lactis NCC2818 in a tractable model of weaning in infants. Piglets were reared by their mothers before being weaned onto a solid diet supplemented with B. lactis NCC2818, while sibling controls did not receive supplementation. Probiotic supplementation resulted in a reduction in IgA (P< 0·0005) and IgM (P< 0·009) production by mucosal tissues but had no effect on IgG production (P>0·05). Probiotic-supplemented pigs had more mast cells than unsupplemented littermates (P< 0·0001), although numbers in both groups were low. In addition, the supplemented piglets made stronger serum IgG responses to fed and injected antigens (P< 0·05). The present findings are consistent with B. lactis NCC2818 reducing intestinal permeability induced by weaning, and suggest that the piglet is a valuable intermediate between rodent models and human infants. The results also strongly suggest that measures of the effect of probiotic supplementation on the immune system need to be interpreted carefully as proxy measures of health benefit. However, they are useful in developing an understanding of the mechanism of action of probiotic strains, an important factor in predicting favourable health outcomes of nutritional intervention.

scholarly journals Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000597 ◽  
Author(s):  
Alberto Cauli ◽  
Grazia Dessole ◽  
Matteo Piga ◽  
Maria Maddalena Angioni ◽  
Silvia Pinna ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Nk Cells ◽  
Natural Killer ◽  
Surface Density ◽  
Surface Expression ◽  
Chronic Inflammatory Disease ◽  
Hla B27 ◽  
Peripheral Blood Mononuclear ◽  
Histocompatibility Complex ◽  
Natural Killer Receptors

BackgroundAnkylosing spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of human leucocyte antigen (HLA)-B27 alleles. HLA-E molecules are non-classical major histocompatibility complex (MHC) class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis.‘’ObjectiveTo analyse the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27-positive patients with AS and healthy controls (HC) bearing the AS-associated B*2705 and the non-AS-associated B*2709 alleles.MethodsThe level of surface expression of HLA-E molecules on CD14+ peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27-negative HC using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3−CD56+ NK cells.ResultsHLA-E expression in CD14+ cells was significantly higher in patients with AS (587.0, IQR 424–830) compared with B*2705 HC (389, IQR 251.3–440.5; p=0.0007), B*2709 HC (294.5, IQR 209.5–422; p=0.0004) and HLA-B27-negative HC (380, IQR 197.3–515.0; p=0.01). A higher number of NK cells expressing NKG2A compared with NKG2C were found in all cohorts analysed, as well as a higher cell surface density.ConclusionThe higher surface level of HLA-E molecules in patients with AS compared with HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis, accounting for the previously reported association between HLA-E and AS.

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