scholarly journals Gut microbiota metabolite regulation of host defenses at mucosal surfaces: implication in precision medicine

2019 ◽  
Vol 2 (2) ◽  
pp. 110-119 ◽  
Author(s):  
Anthony J Bilotta ◽  
Yingzi Cong
Keyword(s):  
Gut Microbiota ◽  
Precision Medicine ◽  
Dietary Fiber ◽  
Histone Deacetylase Inhibitors ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Short Chain Fatty Acids ◽  
Cell Functions ◽  
Inflammatory State ◽  
And Function

Abstract The gut microbiota has a well-established role in the regulation of host homeostasis. Multiple factors control the composition and function of the microbiota. The westernization of diet, a shift away from nutrient-dense foods toward diets high in saturated fats, has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease (IBD). Diet is critical in the development and maintenance of a healthy microbiome, where dietary fiber (found in the highest amounts in fruits, vegetables, and legumes) is metabolized by the microbiome. In turn, the bacterial metabolites of dietary fiber, short chain fatty acids (SCFAs), regulate gut homeostasis. SCFAs engage G-protein coupled receptors (GPRs) and act as histone deacetylase inhibitors (HDACi) to module epithelial and immune cell functions in the intestines, where they generally promote an anti-inflammatory state. This review highlights the functions of SCFAs and their roles in the pathogenesis of IBD to provide insights into their potential therapeutic application for the treatment of IBD for the purposes of precision medicine.

scholarly journals Effects of Altered Dietary Fiber on the Gut Microbiota, Short-Chain Fatty Acids and Cecum of Chickens during Different Growth Periods

2020 ◽  
Author(s):  
Baosheng Sun ◽  
Linyue Hou ◽  
Yu Yang
Keyword(s):  
Gut Microbiota ◽  
Dietary Fiber ◽  
Total Content ◽  
Short Chain Fatty Acids ◽  
Gut Health ◽  
High Fiber ◽  
High Feed ◽  
Long Term Observation ◽  
And Function

Increasing numbers of researchers are interested in the importance of dietary fiber for the gut microbiota, microbiotal metabolite SCFA, energy metabolism and gut health of the host. However, studies have demonstrated that long-term and longitudinal observation may be needed to evaluate the effect of dietary fiber better, and few such works have been made in chickens. Therefore, we successively fed low-fiber, high--fiber and low-fiber diets to two breeds of chickens during different growth periods (1—8, 9—20 and 21—50 weeks), aiming to longitudinally observe the long-term effect of altered dietary fiber on the gut microbiota, SCFA and development of cecum of chickens with age. The results showed that the composition and function of the gut microbiota, SCFA and the development of the cecum were different during different periods, which was largly affected by dietary fiber. However, the causes of some effects were different during the different periods. For example, compared with that in low-fiber chickens at 8 weeks, dominant fiber-degradation bacteria such as Bacteroidetes, Alloprevotella and SCFA-producing bacteria such as Faecalibacterium increased due to a high-fiber diet at 20 weeks, while due to a high feed intake in 50 weeks. Moreover, the concentration of SCFA in 20 weeks was significantly higher than in 8 weeks and 50 weeks, but the causes of this difference were also distinct. It was proposed that a long-term observation was needed to evaluate the effect of dietary fiber better on chickens. The metabolite pathways of ATP-binding cassette (ABC) transporters encoded by Firmicutes were enriched in 8 weeks, while a two-component system and β–glucosidase encoded by Bacteroidetes were enriched in 20 and 50 weeks. The trend was the same in two breeds of chickens except for Alloprevotella. In addition, the total content of SCFA in the contents of cecum was also affected by the size of the cecum. Surprisingly, the length of the cecum shortened from 20—50 weeks, maybe due to reduced dietary fiber.

scholarly journals Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens

Gut ◽  
2017 ◽  
Vol 67 (5) ◽  
pp. 847-859 ◽  
Author(s):  
Allison Cabinian ◽  
Daniel Sinsimer ◽  
May Tang ◽  
Youngsoon Jang ◽  
Bongkum Choi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cells ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Premature Death ◽  
Enteric Pathogens ◽  
Immune Protection ◽  
Intestinal Immunity ◽  
Cell Responses ◽  
And Function

BackgroundInteractions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.AimWe have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.MethodsExpression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium.ResultsSLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.ConclusionsSLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

scholarly journals Gut dysbiosis modulates the immune response to factor VIII in murine hemophilia A

2020 ◽  
Vol 4 (12) ◽  
pp. 2644-2655
Author(s):  
Julie Tarrant ◽  
Matthew Cormier ◽  
Kate Nesbitt ◽  
Courtney Dwyer ◽  
Christine Hough ◽  
...  
Keyword(s):  
Immune Response ◽  
Gut Microbiota ◽  
Hemophilia A ◽  
Immune Cell ◽  
Short Chain Fatty Acids ◽  
Microbial Metabolites ◽  
Oral Supplementation ◽  
Immune Mediated ◽  
Related Risk ◽  
Cell Transcriptome

Abstract The development of neutralizing FVIII antibodies is the most serious complication of hemophilia A treatment. The currently known patient- and treatment-related risk factors for inhibitor development do not accurately predict this adverse event in all patients. The composition of the gut microbiota has been shown to influence immune-mediated diseases at distant anatomical sites (eg, lungs, brain, and joints). We demonstrate that a disrupted gut microbiota can be created in a mouse model of hemophilia A using a broad-spectrum antibiotic. Under controlled conditions, this sustained dysbiosis was associated with an increase in splenic B cells and the development of higher titer, FVIII-specific immunoglobulin G antibodies after FVIII challenge. Splenic and mesenteric lymph node cytokines, T cells, and dendritic cells were unaffected before administration of FVIII. However, the immune transcriptome of both aforementioned secondary lymphoid organs was significantly modified. Short-chain fatty acids (SCFAs), which are immunomodulatory microbial metabolites, were depleted in cecal contents of the dysbiotic mice. Furthermore, supplementation of the drinking water with butyrate, the most immunologically active SCFA, successfully achieved attenuation of the FVIII immune response. Collectively, data from this exploratory study suggest that the composition of the gut microbiota alters the FVIII immune response via the action of specific microbial metabolites on the immune cell transcriptome and that oral supplementation with butyrate effectively reduces the FVIII immune response.

scholarly journals Adiponectin Role in Neurodegenerative Diseases: Focus on Nutrition Review

2020 ◽  
Vol 21 (23) ◽  
pp. 9255
Author(s):  
Rita Polito ◽  
Irene Di Meo ◽  
Michelangela Barbieri ◽  
Aurora Daniele ◽  
Giuseppe Paolisso ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
The Central Nervous System ◽  
Regulatory Effects ◽  
Nutrition Review ◽  
Selective Process

Adiponectin is an adipokine produced by adipose tissue. It has numerous beneficial effects. In particular, it improves metabolic effects and glucose homeostasis, lipid profile, and is involved in the regulation of cytokine profile and immune cell production, having anti-inflammatory and immune-regulatory effects. Adiponectin’s role is already known in immune diseases and also in neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are a set of diseases of the central nervous system, characterized by a chronic and selective process of neuron cell death, which occurs mainly in relation to oxidative stress and neuroinflammation. Lifestyle is able to influence the development of these diseases. In particular, unhealthy nutrition on gut microbiota, influences its composition and predisposition to develop many diseases such as neurodegenerative diseases, given the importance of the “gut-brain” axis. There is a strong interplay between Adiponectin, gut microbiota, and brain-gut axis. For these reasons, a healthy diet composed of healthy nutrients such as probiotics, prebiotics, polyphenols, can prevent many metabolic and inflammatory diseases such as neurodegenerative diseases and obesity. The special Adiponectin role should be taken into account also, in order to be able to use this component as a therapeutic molecule.

scholarly journals Dietary lipids, gut microbiota and lipid metabolism

2019 ◽  
Vol 20 (4) ◽  
pp. 461-472 ◽  
Author(s):  
Marc Schoeler ◽  
Robert Caesar
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Dietary Lipids ◽  
Lipid Levels ◽  
And Function ◽  
Host Metabolism ◽  
Secondary Bile Acids

Abstract The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet properties such as the amount and composition of lipids. Hence, dietary lipids may influence host physiology through interaction with the gut microbiota. Lipids affect the gut microbiota both as substrates for bacterial metabolic processes, and by inhibiting bacterial growth by toxic influence. The gut microbiota has been shown to affect lipid metabolism and lipid levels in blood and tissues, both in mice and humans. Furthermore, diseases linked to dyslipidemia, such as non-alcoholic liver disease and atherosclerosis, are associated with changes in gut microbiota profile. The influence of the gut microbiota on host lipid metabolism may be mediated through metabolites produced by the gut microbiota such as short-chain fatty acids, secondary bile acids and trimethylamine and by pro-inflammatory bacterially derived factors such as lipopolysaccharide. Here we will review the association between gut microbiota, dietary lipids and lipid metabolism

scholarly journals The gut microbiota influences skeletal muscle mass and function in mice

2019 ◽  
Vol 11 (502) ◽  
pp. eaan5662 ◽  
Author(s):  
Shawon Lahiri ◽  
Hyejin Kim ◽  
Isabel Garcia-Perez ◽  
Musarrat Maisha Reza ◽  
Katherine A. Martin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Gut Microbiota ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Neuromuscular Junctions ◽  
Short Chain Fatty Acids ◽  
Germ Free ◽  
Mouse Skeletal Muscle ◽  
And Function

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4. Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

scholarly journals Dendritic Cells and CCR7 Expression; an Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8340
Author(s):  
Emma Probst Brandum ◽  
Astrid Sissel Jørgensen ◽  
Mette Marie Rosenkilde ◽  
Gertrud Malene Hjortø
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Antagonistic Effect ◽  
Lymphoid Tissues ◽  
Chronic Inflammatory Diseases ◽  
Inflammatory Conditions ◽  
Inflammatory State ◽  
And Control

Chemotactic cytokines—chemokines—control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body’s defense system. Many chemokines also participate in pathological processes leading up to and exacerbating the inflammatory state characterizing chronic inflammatory diseases. In this review, we discuss the role of dendritic cells (DCs) and the central chemokine receptor CCR7 in the initiation and sustainment of selected chronic inflammatory diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. We revisit the binary role that CCR7 plays in combatting and progressing cancer, and we discuss how CCR7 and DCs can be harnessed for the treatment of cancer. To provide the necessary background, we review the differential roles of the natural ligands of CCR7, CCL19, and CCL21 and how they direct the mobilization of activated DCs to lymphoid organs and control the formation of associated lymphoid tissues (ALTs). We provide an overview of DC subsets and, briefly, elaborate on the different T-cell effector types generated upon DC–T cell priming. In the conclusion, we promote CCR7 as a possible target of future drugs with an antagonistic effect to reduce inflammation in chronic inflammatory diseases and an agonistic effect for boosting the reactivation of the immune system against cancer in cell-based and/or immune checkpoint inhibitor (ICI)-based anti-cancer therapy.

scholarly journals Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

2021 ◽  
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa Maruthar ◽  
Stephen P Juraschek ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gut Microbiota ◽  
Randomized Trial ◽  
Short Chain Fatty Acids ◽  
Metagenomic Sequencing ◽  
Microbiota Composition ◽  
Behavioral Weight Loss ◽  
Microbiome Composition ◽  
Weight Loss Group ◽  
And Function

<b>Objective:</b> To determine the longer-term effects of metformin and behavioral weight loss on gut microbiota and SCFAs. <p><b>Methods: </b>We conducted a parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n=121) to: 1) metformin (up to 2000mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n=114), 6 months (n=109) and 12 months (n=105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. </p> <p><b>Results: </b>Of the 121 participants, 79% were female, 46% were black, and the mean age was 60y. Only metformin intervention significantly altered microbiota composition. Compared to control, metformin increased <i>E. Coli</i> and <i>Ruminococcus torques</i> and decreased <i>Intestinibacter Bartletti</i> at both 6 and 12 months, and decreased the genus <i>Roseburia (genus)</i>, including <i>R. faecis</i> and <i>R. intestinalis,</i> at 12 months. Effects were similar when comparing metformin to the behavioral weight loss group. Metformin also altered 62 metagenomic functional pathways and increased butyrate, acetate, and valerate at 6 months. Behavioral weight loss vs. control did not significantly alter microbiota composition, but did increase acetate at 6 months. Increases in acetate were associated with decreases in fasting insulin.</p> <p><b>Conclusions:</b> Metformin, but not behavioral weight loss, impacted gut microbiota composition and function at 6 months and 12 months. Both metformin and behavioral weight loss altered 6-month SCFAs, including increasing acetate which correlated with improved insulin sensitivity.</p>

scholarly journals Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation

2020 ◽  
Vol 14 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Aida Iljazovic ◽  
Urmi Roy ◽  
Eric J. C. Gálvez ◽  
Till R. Lesker ◽  
Bei Zhao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Steady State ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Short Chain Fatty Acids ◽  
Host Susceptibility ◽  
Mucosal Inflammation ◽  
Microbial Ecosystem ◽  
Systemic Autoimmunity ◽  
And Function

AbstractDiverse microbial signatures within the intestinal microbiota have been associated with intestinal and systemic inflammatory diseases, but whether these candidate microbes actively modulate host phenotypes or passively expand within the altered microbial ecosystem is frequently not known. Here we demonstrate that colonization of mice with a member of the genus Prevotella, which has been previously associated to colitis in mice, exacerbates intestinal inflammation. Our analysis revealed that Prevotella intestinalis alters composition and function of the ecosystem resulting in a reduction of short-chain fatty acids, specifically acetate, and consequently a decrease in intestinal IL-18 levels during steady state. Supplementation of IL-18 to Prevotella-colonized mice was sufficient to reduce intestinal inflammation. Hence, we conclude that intestinal Prevotella colonization results in metabolic changes in the microbiota, which reduce IL-18 production and consequently exacerbate intestinal inflammation, and potential systemic autoimmunity.

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