Xenobiotic receptors and the regulation of intestinal homeostasis - harnessing the chemical output of the intestinal microbiota

2021 ◽  
Author(s):  
Kristoff M. Nieves ◽  
Simon A. Hirota ◽  
Kyle L. Flannigan
Keyword(s):  
Intestinal Microbiota ◽  
Pregnane X Receptor ◽  
Local Environment ◽  
Tissue Homeostasis ◽  
Commensal Bacteria ◽  
Host Cells ◽  
Symbiotic Relationship ◽  
Microbial Metabolites ◽  
Aryl Hydrocarbon ◽  
Sense And Respond

The commensal bacteria that reside in the gastrointestinal tract exist in a symbiotic relationship with the host, driving the development of the immune system and maintaining metabolic and tissue homeostasis in the local environment. The intestinal microbiota has the capacity to generate a wide array of chemical metabolites to which the cells of the intestinal mucosa are exposed. Host cells express xenobiotic receptors, such as the aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), that can sense and respond to chemicals that are generated by non-host pathways. In this review, we will outline the physiological and immunological processes within the intestinal environment that are regulated by microbial metabolites through the activation of the AhR and PXR, with a focus on ligands generated by the step-wise catabolism of tryptophan.

scholarly journals ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the Gastrointestinal Tract

2018 ◽  
Vol 19 (8) ◽  
pp. 2371 ◽  
Author(s):  
Akie Inami ◽  
Hiroshi Kiyono ◽  
Yosuke Kurashima
Keyword(s):  
T Cells ◽  
Gastrointestinal Tract ◽  
Mast Cells ◽  
Immune Cells ◽  
Purinergic Receptors ◽  
Inflammatory Responses ◽  
Tissue Homeostasis ◽  
Commensal Bacteria ◽  
Host Cells ◽  
Extracellular Nucleotides

Extracellular nucleotides, such as adenosine triphosphate (ATP), are released from host cells including nerve termini, immune cells, injured or dead cells, and the commensal bacteria that reside in the gut lumen. Extracellular ATP interacts with the host through purinergic receptors, and promotes intercellular and bacteria-host communication to maintain the tissue homeostasis. However, the release of massive concentrations of ATP into extracellular compartments initiates acute and chronic inflammatory responses through the activation of immunocompetent cells (e.g., T cells, macrophages, and mast cells). In this review, we focus on the functions of ATP as a pathophysiologic mediator that is required for the induction and resolution of inflammation and inter-species communication.

scholarly journals Microbial Metabolites Determine Host Health and the Status of Some Diseases

2019 ◽  
Vol 20 (21) ◽  
pp. 5296 ◽  
Author(s):  
Panida Sittipo ◽  
Jae-won Shim ◽  
Yun Lee
Keyword(s):  
Intestinal Microbiota ◽  
Metabolic Diseases ◽  
Host Cells ◽  
Microbiota Composition ◽  
Microbial Metabolites ◽  
Gi Tract ◽  
Host Health ◽  
Bowel Diseases ◽  
The Status ◽  
Mutualistic Relationship

The gastrointestinal (GI) tract is a highly complex organ composed of the intestinal epithelium layer, intestinal microbiota, and local immune system. Intestinal microbiota residing in the GI tract engages in a mutualistic relationship with the host. Different sections of the GI tract contain distinct proportions of the intestinal microbiota, resulting in the presence of unique bacterial products in each GI section. The intestinal microbiota converts ingested nutrients into metabolites that target either the intestinal microbiota population or host cells. Metabolites act as messengers of information between the intestinal microbiota and host cells. The intestinal microbiota composition and resulting metabolites thus impact host development, health, and pathogenesis. Many recent studies have focused on modulation of the gut microbiota and their metabolites to improve host health and prevent or treat diseases. In this review, we focus on the production of microbial metabolites, their biological impact on the intestinal microbiota composition and host cells, and the effect of microbial metabolites that contribute to improvements in inflammatory bowel diseases and metabolic diseases. Understanding the role of microbial metabolites in protection against disease might offer an intriguing approach to regulate disease.

scholarly journals Zelluläres Tauziehen: Wie Zellen auf mechanischen Stress antworten

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 385-389
Author(s):  
Kai Weissenbruch ◽  
Marc Hippler ◽  
Martin Bastmeyer
Keyword(s):  
Tissue Homeostasis ◽  
Physical Basis ◽  
Technical Advance ◽  
Molecular Scale ◽  
Sense And Respond ◽  
Intracellular Forces

AbstractThe ability of cells to sense and respond to extracellular forces is critical for cellular and tissue homeostasis. Tension or compression act on our body ubiquitously and cells respond to such mechanical cues by producing intracellular forces on their own. In this article, we briefly highlight the cellular and physical basis driving these phenomena and discuss our recent technical advance to stimulate and monitor the cellular mechanoresponse on a molecular scale.

scholarly journals Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort

mSystems ◽  
2016 ◽  
Vol 1 (5) ◽  
Author(s):  
Antonio Gonzalez ◽  
Embriette Hyde ◽  
Naseer Sangwan ◽  
Jack A. Gilbert ◽  
Erik Viirre ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Health ◽  
Commensal Bacteria ◽  
Common Side Effect ◽  
Symbiotic Relationship ◽  
Link Type ◽  
Downstream Effects ◽  
Reducing Bacteria ◽  
Nitrate Reducing Bacteria ◽  
Nitric Oxide Pathway

ABSTRACT Recent work has demonstrated a potentially symbiotic relationship between oral commensal bacteria and humans through the salivary nitrate-nitrite-nitric oxide pathway (C. Duncan et al., Nat Med 1:546–551, 1995, http://dx.doi.org/10.1038/nm0695-546 ). Oral nitrate-reducing bacteria contribute physiologically relevant levels of nitrite and nitric oxide to the human host that may have positive downstream effects on cardiovascular health (V. Kapil et al., Free Radic Biol Med 55:93–100, 2013, http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.013 ). In the work presented here, we used 16S rRNA Illumina sequencing to determine whether a connection exists between oral nitrate-reducing bacteria, nitrates for cardiovascular disease, and migraines, which are a common side effect of nitrate medications (U. Thadani and T. Rodgers, Expert Opin Drug Saf 5:667–674, 2006, http://dx.doi.org/10.1517/14740338.5.5.667 ). Nitrates, such as cardiac therapeutics and food additives, are common headache triggers, with nitric oxide playing an important role. Facultative anaerobic bacteria in the oral cavity may contribute migraine-triggering levels of nitric oxide through the salivary nitrate-nitrite-nitric oxide pathway. Using high-throughput sequencing technologies, we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples. IMPORTANCE Recent work has demonstrated a potentially symbiotic relationship between oral commensal bacteria and humans through the salivary nitrate-nitrite-nitric oxide pathway (C. Duncan et al., Nat Med 1:546–551, 1995, http://dx.doi.org/10.1038/nm0695-546 ). Oral nitrate-reducing bacteria contribute physiologically relevant levels of nitrite and nitric oxide to the human host that may have positive downstream effects on cardiovascular health (V. Kapil et al., Free Radic Biol Med 55:93–100, 2013, http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.013 ). In the work presented here, we used 16S rRNA Illumina sequencing to determine whether a connection exists between oral nitrate-reducing bacteria, nitrates for cardiovascular disease, and migraines, which are a common side effect of nitrate medications (U. Thadani and T. Rodgers, Expert Opin Drug Saf 5:667–674, 2006, http://dx.doi.org/10.1517/14740338.5.5.667 ).

scholarly journals Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis

2017 ◽  
Vol 114 (38) ◽  
pp. 10178-10183 ◽  
Author(s):  
Hana Sarashina-Kida ◽  
Hideo Negishi ◽  
Junko Nishio ◽  
Wataru Suda ◽  
Yuki Nakajima ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Local Environment ◽  
Surfactant Protein ◽  
Commensal Bacteria ◽  
Intestinal Lumen ◽  
Surfactant Protein D ◽  
Organ Systems ◽  
Notable Increase ◽  
Health And Disease ◽  
Deficient Mice

The commensal microbiota within the gastrointestinal tract is essential in maintaining homeostasis. Indeed, dysregulation in the repertoire of microbiota can result in the development of intestinal immune–inflammatory diseases. Further, this immune regulation by gut microbiota is important systemically, impacting health and disease of organ systems beyond the local environment of the gut. What has not been explored is how distant organs might in turn shape the microbiota via microbe-targeted molecules. Here, we provide evidence that surfactant protein D (SP-D) synthesized in the gallbladder and delivered into intestinal lumen binds selectively to species of gut commensal bacteria. SP-D–deficient mice manifest intestinal dysbiosis and show a susceptibility to dextran sulfate sodium-induced colitis. Further, fecal transfer from SP-D–deficient mice to wild-type, germ-free mice conveyed colitis susceptibility. Interestingly, colitis caused a notable increase inSftpdgene expression in the gallbladder, but not in the lung, via the activity of glucocorticoids produced in the liver. These findings describe a unique mechanism of interorgan regulation of intestinal immune homeostasis by SP-D with potential clinical implications such as cholecystectomy.

scholarly journals The Mast Cell-Aryl Hydrocarbon Receptor Interplay at the Host-Microbe Interface

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Claudio Costantini ◽  
Giorgia Renga ◽  
Vasilis Oikonomou ◽  
Giuseppe Paolicelli ◽  
Monica Borghi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Current Knowledge ◽  
Cell Physiology ◽  
Effector Functions ◽  
Host Protection ◽  
Aryl Hydrocarbon ◽  
Environmental Agents ◽  
Sense And Respond

Mast cells are increasingly being recognized as crucial cells in the response of the organism to environmental agents. Interestingly, the ability of mast cells to sense and respond to external cues is modulated by the microenvironment that surrounds mast cells and influences their differentiation. The scenario that is emerging unveils a delicate equilibrium that balances the effector functions of mast cells to guarantee host protection without compromising tissue homeostasis. Among the environmental components able to mold mast cells and fine-tune their effector functions, the microorganisms that colonize the human body, collectively known as microbiome, certainly play a key role. Indeed, microorganisms can regulate not only the survival, recruitment, and maturation of mast cells but also their activity by setting the threshold required for the exploitation of their different effector functions. Herein, we summarize the current knowledge about the mechanisms underlying the ability of the microorganisms to regulate mast cell physiology and discuss potential deviations that result in pathological consequences. We will discuss the pivotal role of the aryl hydrocarbon receptor in sensing the environment and shaping mast cell adaptation at the host-microbe interface.

scholarly journals Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation

2021 ◽  
Author(s):  
Morteza Aramesh ◽  
Diana Stoycheva ◽  
Ioana Sandu ◽  
Stephan J. Ihle ◽  
Tamara Zund ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cell Signaling ◽  
T Cell Activation ◽  
Cell Activation ◽  
Local Environment ◽  
T Cell Signaling ◽  
Sense And Respond ◽  
Altered Gene

T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanisms by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation, and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200 nm pores, but not in 400 nm pores. Consequently, formation of TCR nanoclustered hotspots within 200 nm pores, allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.

scholarly journals Pathogenetic Substantiation of the Therapeutic Impact on Microbiota in Irritable Bowel Syndrome

2019 ◽  
Vol 29 (4) ◽  
pp. 7-14
Author(s):  
Yu. O. Shulpekova ◽  
G. H. Babaeva ◽  
V. Yu. Rusyaev
Keyword(s):  
Irritable Bowel Syndrome ◽  
Intestinal Microbiota ◽  
Intestinal Bacteria ◽  
Host Cells ◽  
Intestinal Microbiome ◽  
Bacterial Strains ◽  
Blastocystis Hominis ◽  
Therapeutic Impact ◽  
Irritable Bowel ◽  
Positive Effect

Aim. This review aims to describe the nature of changes in the intestinal microbiota in irritable bowel syndrome (IBS) and provide a pathogenetic justification of the feasibility of a therapeutic impact on microbiota. General findings. An important aspect of the interaction of intestinal bacteria with the “host” cells is their contact with pattern recognition receptors of enterocytes, dendritic cell receptors, as well as a transcellular transport of antigens in the region of Peyer’s patches. The area of interaction of intestinal bacteria and the human body is not limited to the intestines. Intestinal bacteria demonstrate a significant humoral effect due to signalling molecules, some of which exhibit neurotransmitter properties. The study of the bacterial cross-feeding for various species, i.e. mutual use of nutrient substrates produced by bacteria of various species, is of a great interest. The development of a lowactivity inflammation in IBS can partly be explained by the increased interaction of flagellin with the corresponding receptor, as well as the influx of excess bacteria from the small intestine. The majority of studies on IBS have demonstrated the predominance of intestinal bacteria with pro-inflammatory potential (Enterobacteriaceae) and the lack of bacteria with a pronounced anti-inflammatory, antimicrobial and enzymatic action (Lactobacillus and Bifidobacterium), as well as increased mucus degradation. Similar changes are observed in inflammatory bowel diseases. Reduced microbial diversity increases susceptibility to intestinal infections and parasitoses, including those caused by protozoa conditionally pathogenic for adults, such as Blastocystis hominis hominis, Dientamoeba fragilis, Giardia lamblia. With the help of nutrition correction, the use of probiotics and functional foods containing certain probiotic strains, plant fibres (primarily psyllium) and, in some cases, nonabsorbable antibiotics, a positive effect can be achieved in a significant number of IBS patients. Recent works have shown that clinical improvement is accompanied by a change in the composition of the intestinal microbiota.Conclusion. For the pathogenetic treatment of irritable bowel syndrome, the use of non-drug treatment is justified, such as diet optimization and prescription of plant fibres and probiotic bacterial strains. The positive effect of such an approach is largely determined by modification of the intestinal microbiota composition. This opens up prospects for a further, more targeted impact on the intestinal microbiome.

scholarly journals Inhibition of Fibroblast Apoptosis by Borrrelia afzelii, Coxiella burnetii and Bartonella henselae

2011 ◽  
Vol 60 (3) ◽  
pp. 269-272 ◽  
Author(s):  
TOMASZ CHMIELEWSKI ◽  
STANISŁAWA TYLEWSKA-WIERZBANOWSKA
Keyword(s):  
Cell Death ◽  
Chronic Disease ◽  
Coxiella Burnetii ◽  
Caspase 3 ◽  
Bartonella Henselae ◽  
Tissue Homeostasis ◽  
Host Cells ◽  
Fibroblast Cells ◽  
Human Fibroblast Cells ◽  
Long Time

Apoptosis is a genetically controlled mechanism of cell death involved in the regulation of tissue homeostasis. The aim of this study was to investigate the influence of Borrelia afzelii, Coxiella burnetii, and Bartonella henselae bacteria on apoptosis measured as the level of caspase 3 activity in human fibroblast cells HEL-299. Our findings show that C. burnetii bacteria may inhibit the process of apoptosis in the host cells for a long time. This can permit intracellular survival in the host and mediatingthe development of chronic disease.

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