Effect of Antibiotic Treatment on the Intestinal Metabolome

ABSTRACTThe importance of the mammalian intestinal microbiota to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial communities need to be characterized in molecular detail if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.

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Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective

Cancers ◽

10.3390/cancers13030399 ◽

2021 ◽

Vol 13 (3) ◽

pp. 399

Author(s):

Géraldine Gentric ◽

Fatima Mechta-Grigoriou

Keyword(s):

Tumor Cells ◽

Metabolic Pathways ◽

Molecular Mechanisms ◽

Carbon Sources ◽

Cancer Associated Fibroblasts ◽

The Past ◽

Cancer Field ◽

Metabolic Heterogeneity ◽

The Impact ◽

Shed Light

During the past decades, metabolism and redox imbalance have gained considerable attention in the cancer field. In addition to the well-known Warburg effect occurring in tumor cells, numerous other metabolic deregulations have now been reported. Indeed, metabolic reprograming in cancer is much more heterogeneous than initially thought. In particular, a high diversity of carbon sources used by tumor cells has now been shown to contribute to this metabolic heterogeneity in cancer. Moreover, the molecular mechanisms newly highlighted are multiple and shed light on novel actors. Furthermore, the impact of this metabolic heterogeneity on tumor microenvironment has also been an intense subject of research recently. Here, we will describe the new metabolic pathways newly uncovered in tumor cells. We will also have a particular focus on Cancer-Associated Fibroblasts (CAF), whose identity, function and metabolism have been recently under profound investigation. In that sense, we will discuss about the metabolic crosstalk between tumor cells and CAF.

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Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

eLife ◽

10.7554/elife.33070 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 37

Author(s):

Roman M Stilling ◽

Gerard M Moloney ◽

Feargal J Ryan ◽

Alan E Hoban ◽

Thomaz FS Bastiaanssen ◽

...

Keyword(s):

Social Interaction ◽

Social Behaviour ◽

Rna Splicing ◽

Molecular Mechanisms ◽

Autism Spectrum ◽

Gene Expression Response ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Expression Response ◽

Multiple Species

Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs).

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Zebrafish and Medaka: Two Teleost Models of T-Cell and Thymic Development

International Journal of Molecular Sciences ◽

10.3390/ijms20174179 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4179 ◽

Cited By ~ 4

Author(s):

Baubak Bajoghli ◽

Advaita M. Dick ◽

Annisa Claasen ◽

Larissa Doll ◽

Narges Aghaallaei

Keyword(s):

T Cell ◽

Molecular Mechanisms ◽

T Cell Development ◽

Model Systems ◽

Biological Processes ◽

Direct Visualization ◽

Thymic Development ◽

The Past ◽

Shed Light

Over the past two decades, studies have demonstrated that several features of T-cell and thymic development are conserved from teleosts to mammals. In particular, works using zebrafish (Danio rerio) and medaka (Oryzias latipes) have shed light on the cellular and molecular mechanisms underlying these biological processes. In particular, the ease of noninvasive in vivo imaging of these species enables direct visualization of all events associated with these processes, which are, in mice, technically very demanding. In this review, we focus on defining the similarities and differences between zebrafish and medaka in T-cell development and thymus organogenesis; and highlight their advantages as two complementary model systems for T-cell immunobiology and modeling of human diseases.

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From Nursery to Nursing Home: Emerging Concepts in Clostridioides difficile Pathogenesis

Infection and Immunity ◽

10.1128/iai.00934-19 ◽

2020 ◽

Vol 88 (7) ◽

Author(s):

Alexander B. Smith ◽

Joshua Soto Ocana ◽

Joseph P. Zackular

Keyword(s):

Pharmaceutical Drugs ◽

Human Gastrointestinal Tract ◽

Content Type ◽

The Past ◽

Clostridioides Difficile ◽

Wide Range ◽

Pediatric Populations ◽

The Impact ◽

Shed Light

ABSTRACT Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium that infects the human gastrointestinal tract, causing a wide range of disorders that vary in severity from mild diarrhea to toxic megacolon and/or death. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically in both the pediatric and adult populations. The factors driving this rapidly evolving epidemiology remain largely unknown but are likely due in part to previously unappreciated host, microbiota, and environmental factors. In this review, we will cover the risks and challenges of CDI in adult and pediatric populations and examine asymptomatic colonization in infants. We will also discuss the emerging role of diet, pharmaceutical drugs, and pathogen-microbiota interactions in C. difficile pathogenesis, as well as the impact of host-microbiota interactions in the manifestation of C. difficile-associated disease. Finally, we highlight new areas of research and novel strategies that may shed light on this complex infection and provide insights into the future of microbiota-based therapeutics for CDI.

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A New C-Type Lectin Similar to the Human Immunoreceptor DC-SIGN Mediates Symbiont Acquisition by a Marine Nematode

Applied and Environmental Microbiology ◽

10.1128/aem.72.4.2950-2956.2006 ◽

2006 ◽

Vol 72 (4) ◽

pp. 2950-2956 ◽

Cited By ~ 83

Author(s):

Silvia Bulgheresi ◽

Irma Schabussova ◽

Tie Chen ◽

Nicholas P. Mullin ◽

Rick M. Maizels ◽

...

Keyword(s):

Molecular Mechanisms ◽

Marine Nematode ◽

Mannose Binding Protein ◽

Mannose Binding ◽

Marine Symbiosis ◽

Microbe Interactions ◽

Sulfur Oxidizing ◽

Host Microbe Interactions ◽

Symbiont Acquisition

ABSTRACT Although thiotrophic symbioses have been intensively studied for the last three decades, nothing is known about the molecular mechanisms of symbiont acquisition. We used the symbiosis between the marine nematode Laxus oneistus and sulfur-oxidizing bacteria to study this process. In this association a monolayer of symbionts covers the whole cuticle of the nematode, except its anterior-most region. Here, we identify a novel Ca2+-dependent mannose-specific lectin that was exclusively secreted onto the posterior, bacterium-associated region of L. oneistus cuticle. A recombinant form of this lectin induced symbiont aggregation in seawater and was able to compete with the native lectin for symbiont binding in vivo. Surprisingly, the carbohydrate recognition domain of this mannose-binding protein was similar both structurally and functionally to a human dendritic cell-specific immunoreceptor. Our results provide a molecular link between bacterial symbionts and host-secreted mucus in a marine symbiosis and suggest conservation in the mechanisms of host-microbe interactions throughout the animal kingdom.

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Intestinal Microbiota: Facts and Fiction

Digestive Diseases ◽

10.1159/000449095 ◽

2017 ◽

Vol 35 (1-2) ◽

pp. 139-147 ◽

Cited By ~ 14

Author(s):

Miloslav Kverka ◽

Helena Tlaskalová-Hogenová

Keyword(s):

Inflammatory Diseases ◽

Research Directions ◽

Vast Number ◽

Chronic Inflammatory Diseases ◽

Immune Mediated ◽

Complex Ecosystem ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

The Impact ◽

Number Of Bacteria

In humans, the gut microbiota forms a complex ecosystem consisting of a vast number of bacteria, Archaea, fungi and viruses. It represents a major stimulus to the development of the immune system and many other physiological functions, so that it may shape the individual's susceptibility to infectious and immune-mediated diseases. The emergence of new ‘-omics' methods recently revolutionized the way we study the host-microbe interactions, but they also raised new questions and issues. In this review, we discuss the impact of these new data on the current and future therapies for chronic inflammatory diseases. We also outline the major conceptual, technical and interpretational issues that recently led to some misleading conclusions and discuss in brief the current research directions in the field.

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Irf4-dependent CD103+CD11b+dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus

Gut ◽

10.1136/gutjnl-2017-313856 ◽

2017 ◽

Vol 66 (12) ◽

pp. 2110-2120 ◽

Cited By ~ 18

Author(s):

Judith-Mira Pohl ◽

Sebastian Gutweiler ◽

Stephanie Thiebes ◽

Julia K Volke ◽

Ludger Klein-Hitpass ◽

...

Keyword(s):

Dendritic Cells ◽

Antibiotic Treatment ◽

Intestinal Microbiota ◽

Postoperative Ileus ◽

Intestinal Microbiome ◽

Oral Antibiotic ◽

Monocytes And Macrophages ◽

Intestinal Peristalsis ◽

The Impact

ObjectivePostoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction.DesignPOI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball. The impact of the microbiota on intestinal peristalsis was evaluated after oral antibiotic treatment.ResultsWe found thatCd11c-Cre+Irf4flox/floxmice lack CD103+CD11b+DCs, a DC subset unique to the intestine whose function is poorly understood. Their absence in the intestinal muscularis reduced pathogenic inducible nitric oxide synthase (iNOS) production by monocytes and macrophages and ameliorated POI. Pathogenic iNOS was produced in the jejunum by resident Ly6C–macrophages and infiltrating chemokine receptor 2-dependent Ly6C+monocytes, but in the colon only by the latter demonstrating differential tolerance mechanisms along the intestinal tract. Consistently, depletion of both cell subsets reduced small intestinal POI, whereas the depletion of Ly6C+monocytes alone was sufficient to prevent large intestinal POI. The differential role of monocytes and macrophages in small and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI.ConclusionsOur findings reveal that CD103+CD11b+DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes and macrophages and for dysregulating intestinal motility in POI.

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Abdominal Aortic Aneurysm: Roles of Inflammatory Cells

Frontiers in Immunology ◽

10.3389/fimmu.2020.609161 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhen Yuan ◽

Yi Lu ◽

Jia Wei ◽

Jiaqi Wu ◽

Jin Yang ◽

...

Keyword(s):

Molecular Mechanisms ◽

Inflammatory Cells ◽

Aortic Aneurysms ◽

Interaction Networks ◽

Pharmacological Interventions ◽

The Past ◽

Extracellular Traps ◽

Abdominal Aortic ◽

Direct Cell ◽

New Strategies

Abdominal aortic aneurysms (AAAs) are local dilations of infrarenal segment of aortas. Molecular mechanisms underlying the pathogenesis of AAA remain not fully clear. However, inflammation has been considered as a central player in the development of AAA. In the past few decades, studies demonstrated a host of inflammatory cells, including T cells, macrophages, dendritic cells, neutrophils, B cells, and mast cells, etc. infiltrating into aortic walls, which implicated their crucial roles. In addition to direct cell contacts and cytokine or protease secretions, special structures like inflammasomes and neutrophil extracellular traps have been investigated to explore their functions in aneurysm formation. The above-mentioned inflammatory cells and associated structures may initiate and promote AAA expansion. Understanding their impacts and interaction networks formation is meaningful to develop new strategies of screening and pharmacological interventions for AAA. In this review, we aim to discuss the roles and mechanisms of these inflammatory cells in AAA pathogenesis.

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Modern Approaches to Acellular Therapy in Bone and Dental Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms222413454 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13454

Author(s):

Alexey A. Ivanov ◽

Alla V. Kuznetsova ◽

Olga P. Popova ◽

Tamara I. Danilova ◽

Oleg O. Yanushevich

Keyword(s):

Regenerative Medicine ◽

Tissue Repair ◽

Molecular Mechanisms ◽

Therapeutic Agents ◽

Free Products ◽

The Past ◽

Decellularized Extracellular Matrix ◽

Cell Mobilization ◽

Internal Potential ◽

New Strategies

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration.

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What Impact does Internet of Things have on Project Management in Project based Firms?

Asian Business Review ◽

10.18034/abr.v6i3.520 ◽

2016 ◽

Vol 6 (3) ◽

pp. 179-186 ◽

Cited By ~ 1

Author(s):

Siddhartha Vadlamudi

Keyword(s):

Project Management ◽

Qualitative Method ◽

Organizational Goals ◽

Critical Elements ◽

The Past ◽

The Impact ◽

Project Lifecycle ◽

It Skills ◽

Efficiency And Productivity ◽

New Strategies

The highest benefit of IT spans through the enabling of personnel to attain their organizational goals. However, acquiring the IT skills that were not aware of in the past will boost and enhance the personnel for greater performance. IoT technology gives understanding from novel data generated and gives solutions. Therefore, allowing organizations to access new strategies via technological innovation will bring about efficiency and productivity with the project lifecycle. However, this project aimed at assessing the impact of IoT on PM in project-based organizations. A qualitative method of investigation was adopted through interviews and discussions with 9 selected respondents. The result shows the benefit and the usefulness of IoT in project-based organizations. This was assessed using the five project management model namely initiating, planning, executing, control and monitoring, and closing. It is established that the impact of IoT can be seen using any of the five stages. Hence, this study identifies the most critical elements of any project-based organization to include people, possessing on personnel and how their impact the invention of project-based organizations.

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