scholarly journals Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Amber G. Bozward ◽  
Vincenzo Ronca ◽  
Daniel Osei-Bordom ◽  
Ye Htun Oo
Keyword(s):  
Immune Cells ◽  
Gut Microbiome ◽  
Central Element ◽  
Integrated System ◽  
Immune Homeostasis ◽  
Continuous Exposure ◽  
Reciprocal Regulation ◽  
Future Direction ◽  
Tolerance Breakdown ◽  
Tight Correlation

The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.

scholarly journals Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

2019 ◽  
Vol 7 (10) ◽  
pp. 456 ◽  
Author(s):  
Kaliyan Barathikannan ◽  
Ramachandran Chelliah ◽  
Momna Rubab ◽  
Eric Banan-Mwine Daliri ◽  
Fazle Elahi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
Genetic Profile ◽  
Fecal Transplantation ◽  
Intestinal Microbes ◽  
Prevalence Of Obesity ◽  
Future Direction ◽  
The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

scholarly journals Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Ding-Lei Su ◽  
Zhi-Min Lu ◽  
Min-Ning Shen ◽  
Xia Li ◽  
Ling-Yun Sun
Keyword(s):  
Complex Network ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Immune Homeostasis ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Autoimmune Inflammatory Disease ◽  
Anti Inflammatory

SLE is an autoimmune inflammatory disease in which various pro- and anti-inflammatory cytokines, including TGF-β, IL-10, BAFF, IL-6, IFN-α, IFN-γ, IL-17, and IL-23, play crucial pathogenic roles. Virtually, all these cytokines can be generated by both innate and adaptive immune cells and exert different effects depending on specific local microenvironment. They can also interact with each other, forming a complex network to maintain delicate immune homeostasis. In this paper, we elaborate on the abnormal secretion and functions of these cytokines in SLE, analyze their potential pathogenic roles, and probe into the possibility of them being utilized as targets for therapy.

scholarly journals Targeting Negative and Positive Immune Checkpoints with Monoclonal Antibodies in Therapy of Cancer

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1756 ◽  
Author(s):  
Katsiaryna Marhelava ◽  
Zofia Pilch ◽  
Malgorzata Bajor ◽  
Agnieszka Graczyk-Jarzynka ◽  
Radoslaw Zagozdzon
Keyword(s):  
Monoclonal Antibodies ◽  
Immune Cells ◽  
Combined Treatment ◽  
Adaptive Immune Response ◽  
Bispecific Antibodies ◽  
Immune Checkpoints ◽  
Immune Homeostasis ◽  
Physiological Conditions ◽  
Adaptive Immune ◽  
Current State

The immune checkpoints are regulatory molecules that maintain immune homeostasis in physiological conditions. By sending T cells a series of co-stimulatory or co-inhibitory signals via receptors, immune checkpoints can both protect healthy tissues from adaptive immune response and activate lymphocytes to remove pathogens effectively. However, due to their mode of action, suppressive immune checkpoints may serve as unwanted protection for cancer cells. To restore the functioning of the immune system and make the patient’s immune cells able to recognize and destroy tumors, monoclonal antibodies are broadly used in cancer immunotherapy to block the suppressive or to stimulate the positive immune checkpoints. In this review, we aim to present the current state of application of monoclonal antibodies in clinics, used either as single agents or in a combined treatment. We discuss the limitations of these therapies and possible problem-solving with combined treatment approaches involving both non-biological and biological agents. We also highlight the most promising strategies based on the use of monoclonal or bispecific antibodies targeted on immune checkpoints other than currently implemented in clinics.

scholarly journals Gut reactions: How the blood–brain barrier connects the microbiome and the brain

2017 ◽  
Vol 243 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Aric F Logsdon ◽  
Michelle A Erickson ◽  
Elizabeth M Rhea ◽  
Therese S Salameh ◽  
William A Banks
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Cns Disease ◽  
Blood Brain

A growing body of evidence indicates that the microbiome interacts with the central nervous system (CNS) and can regulate many of its functions. One mechanism for this interaction is at the level of the blood–brain barriers (BBBs). In this minireview, we examine the several ways the microbiome is known to interact with the CNS barriers. Bacteria can directly release factors into the systemic circulation or can translocate into blood. Once in the blood, the microbiome and its factors can alter peripheral immune cells to promote interactions with the BBB and ultimately with other elements of the neurovascular unit. Bacteria and their factors or cytokines and other immune-active substances released from peripheral sites under the influence of the microbiome can cross the BBB, alter BBB integrity, change BBB transport rates, or induce release of neuroimmune substances from the barrier cells. Metabolic products produced by the microbiome, such as short-chain fatty acids, can cross the BBB to affect brain function. Through these and other mechanisms, microbiome–BBB interactions can influence the course of diseases as illustrated by multiple sclerosis. Impact statement The connection between the gut microbiome and central nervous system (CNS) disease is not fully understood. Host immune systems are influenced by changes to the microbiota and offers new treatment strategies for CNS disease. Preclinical studies provide evidence of changes to the blood–brain barrier when animals are subject to experimental gut infection or when the animals lack a normal gut microbiome. The intestine also contains a barrier, and bacterial factors can translocate to the blood and interact with host immune cells. These metastatic bacterial factors can signal T-cells to become more CNS penetrant, thus providing a novel intervention for treating CNS disease. Studies in humans show the therapeutic effects of T-cell engineering for the treatment of leukemia, so perhaps a similar approach for CNS disease could prove effective. Future research should begin to define the bacterial species that can cause immune cells to differentiate and how these interactions vary amongst CNS disease models.

scholarly journals The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangjun Liu ◽  
Ye Cheng ◽  
Dan Zang ◽  
Min Zhang ◽  
Xiuhua Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Fecal Microbiota ◽  
Immune Homeostasis ◽  
Gut Dysbiosis ◽  
Underlying Mechanisms ◽  
And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

scholarly journals Eavesdropping on the conversation between immune cells and the skin epithelium

2019 ◽  
Vol 31 (7) ◽  
pp. 415-422 ◽  
Author(s):  
Shoiab Bukhari ◽  
Aaron F Mertz ◽  
Shruti Naik
Keyword(s):  
Immune Cells ◽  
Immune Surveillance ◽  
External Environment ◽  
Immune Functions ◽  
Skin Epithelium ◽  
Epithelial Homeostasis ◽  
Inflammatory Stimuli ◽  
Tolerance Breakdown ◽  
Context Specific ◽  
And Function

Abstract The skin epithelium covers our body and serves as a vital interface with the external environment. Here, we review the context-specific interactions between immune cells and the epithelium that underlie barrier fitness and function. We highlight the mechanisms by which these two systems engage each other and how immune–epithelial interactions are tuned by microbial and inflammatory stimuli. Epithelial homeostasis relies on a delicate balance of immune surveillance and tolerance, breakdown of which results in disease. In addition to their canonical immune functions, resident and recruited immune cells also supply the epithelium with instructive signals to promote repair. Decoding the dialogue between immunity and the epithelium therefore has great potential for boosting barrier function or mitigating inflammatory epithelial diseases.

scholarly journals Interactions between the Gut Microbiome, Lung Conditions, and Coronary Heart Disease and How Probiotics Affect These

2021 ◽  
Vol 22 (18) ◽  
pp. 9700
Author(s):  
Trudy M. Wassenaar ◽  
Valentina A. Juncos ◽  
Kurt Zimmermann
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Immune Cells ◽  
Gut Microbiome ◽  
Chronic Conditions ◽  
Heart Diseases ◽  
Short Chain Fatty Acids ◽  
Coronary Heart Diseases

The importance of a healthy microbiome cannot be overemphasized. Disturbances in its composition can lead to a variety of symptoms that can extend to other organs. Likewise, acute or chronic conditions in other organs can affect the composition and physiology of the gut microbiome. Here, we discuss interorgan communication along the gut–lung axis, as well as interactions between lung and coronary heart diseases and between cardiovascular disease and the gut microbiome. This triangle of organs, which also affects the clinical outcome of COVID-19 infections, is connected by means of numerous receptors and effectors, including immune cells and immune-modulating factors such as short chain fatty acids (SCFA) and trimethlamine–N–oxide (TMAO). The gut microbiome plays an important role in each of these, thus affecting the health of the lungs and the heart, and this interplay occurs in both directions. The gut microbiome can be influenced by the oral uptake of probiotics. With an improved understanding of the mechanisms responsible for interorgan communication, we can start to define what requirements an ‘ideal’ probiotic should have and its role in this triangle.

The Gut Microbiome in Hypertension

2021 ◽  
Vol 128 (7) ◽  
pp. 934-950
Author(s):  
Ellen G. Avery ◽  
Hendrik Bartolomaeus ◽  
Andras Maifeld ◽  
Lajos Marko ◽  
Helge Wiig ◽  
...  
Keyword(s):  
Immune Cells ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
The Body ◽  
Model Systems ◽  
Future Research ◽  
Hypertensive Disease ◽  
Preclinical Research ◽  
Ongoing Research ◽  
Diverse Range

The pathogenesis of hypertension is known to involve a diverse range of contributing factors including genetic, environmental, hormonal, hemodynamic and inflammatory forces, to name a few. There is mounting evidence to suggest that the gut microbiome plays an important role in the development and pathogenesis of hypertension. The gastrointestinal tract, which houses the largest compartment of immune cells in the body, represents the intersection of the environment and the host. Accordingly, lifestyle factors shape and are modulated by the microbiome, modifying the risk for hypertensive disease. One well-studied example is the consumption of dietary fibers, which leads to the production of short-chain fatty acids and can contribute to the expansion of anti-inflammatory immune cells, consequently protecting against the progression of hypertension. Dietary interventions such as fasting have also been shown to impact hypertension via the microbiome. Studying the microbiome in hypertensive disease presents a variety of unique challenges to the use of traditional model systems. Integrating microbiome considerations into preclinical research is crucial, and novel strategies to account for reciprocal host-microbiome interactions, such as the wildling mouse model, may provide new opportunities for translation. The intricacies of the role of the microbiome in hypertensive disease is a matter of ongoing research, and there are several technical considerations which should be accounted for moving forward. In this review we provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure. Additionally, we provide recommendations for ongoing and future research, such that important insights from the microbiome field at large can be readily integrated in the context of hypertension.

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