scholarly journals Phages and Their Role in Gastrointestinal Disease: Focus on Inflammatory Bowel Disease

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1013 ◽  
Author(s):  
Martin Maronek ◽  
Rene Link ◽  
Lubos Ambro ◽  
Roman Gardlik
Keyword(s):  
Molecular Mechanisms ◽  
Phage Therapy ◽  
Gastrointestinal Disease ◽  
Intestinal Microbiome ◽  
Bowel Diseases ◽  
Gut Mucosa ◽  
Inflammatory Bowel ◽  
Main Factors ◽  
Disease Focus

Inflammatory bowel diseases (IBDs) are a group of chronic autoinflammatory diseases including Crohn’s disease and ulcerative colitis. Although the molecular mechanisms governing the pathogenesis of gastrointestinal inflammation are not completely clear, the main factors are presumed to be genetic predisposition, environmental exposure, and the intestinal microbiome. Hitherto, most of the studies focusing on the role of the microbiome studied the action and effect of bacteria. However, the intestinal microbiome comprises other members of the microbial community as well, namely, fungi, protozoa, and viruses. We believe that bacteriophages are among the main orchestrators of the effect of microbiota on the gut mucosa. Therefore, this review aims to summarize the knowledge of the role of intestinal phageome in IBD and to discuss the concept of phage therapy and its future applications.

scholarly journals Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Lingling Qv ◽  
Sunbing Mao ◽  
Yongjun Li ◽  
Jia Zhang ◽  
Lanjuan Li
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Bowel Disease ◽  
Bacterial Population ◽  
Molecular Mechanisms ◽  
Host Immune Response ◽  
Intestinal Microbiome ◽  
Inflammatory Bowel ◽  
Main Factors

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, are chronic, relapsing intestinal inflammatory disorders. Although the molecular mechanisms governing the pathogenesis of IBD are not completely clear, the main factors are presumed to be a complex interaction between genetic predisposition, host immune response and environmental exposure, especially the intestinal microbiome. Currently, most studies have focused on the role of gut bacteria in the onset and development of IBD, whereas little attention has been paid to the enteroviruses. Among of them, viruses that infect prokaryotes, called bacteriophages (phages) occupy the majority (90%) in population. Moreover, several recent studies have reported the capability of regulating the bacterial population in the gut, and the direct and indirect influence on host immune response. The present review highlights the roles of gut phages in IBD pathogenesis and explores the potentiality of phages as a therapeutic target for IBD treatment.

scholarly journals Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

2019 ◽  
Vol 116 (52) ◽  
pp. 26717-26726 ◽  
Author(s):  
Paola Menghini ◽  
Daniele Corridoni ◽  
Ludovica F. Buttó ◽  
Abdullah Osme ◽  
Sushma Shivaswamy ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Intestinal Microbiome ◽  
Lactobacillus Salivarius ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Antiinflammatory Effects

Crohn’s disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosa-associated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn’s-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti–IL-1α administration led to a decreased ratio ofProteobacteriatoBacteroidetes, decreased presence ofHelicobacterspecies, and elevated representation ofMucispirillum schaedleriandLactobacillus salivarius. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α–based therapies.

scholarly journals Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor

2021 ◽  
Author(s):  
Yan Wei ◽  
Lijia Chang ◽  
Kenji Hashimoto
Keyword(s):  
Psychiatric Disorders ◽  
Molecular Mechanisms ◽  
The United States ◽  
Racemic Mixture ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Resistant Depression ◽  
The Brain ◽  
Related Compounds

AbstractThe discovery of robust antidepressant actions exerted by the N-methyl-D-aspartate receptor (NMDAR) antagonist (R,S)-ketamine has been a crucial breakthrough in mood disorder research. (R,S)-ketamine is a racemic mixture of equal amounts of (R)-ketamine (arketamine) and (S)-ketamine (esketamine). In 2019, an esketamine nasal spray from Johnson & Johnson was approved in the United States of America and Europe for treatment-resistant depression. However, an increasing number of preclinical studies show that arketamine has greater potency and longer-lasting antidepressant-like effects than esketamine in rodents, despite the lower binding affinity of arketamine for the NMDAR. In clinical trials, non-ketamine NMDAR-related compounds did not exhibit ketamine-like robust antidepressant actions in patients with depression, despite these compounds showing antidepressant-like effects in rodents. Thus, the rodent data do not necessarily translate to humans due to the complexity of human psychiatric disorders. Collectively, the available studies indicate that it is unlikely that NMDAR plays a major role in the antidepressant action of (R,S)-ketamine and its enantiomers, although the precise molecular mechanisms underlying antidepressant actions of (R,S)-ketamine and its enantiomers remain unclear. In this paper, we review recent findings on the molecular mechanisms underlying the antidepressant actions of (R,S)-ketamine and its potent enantiomer arketamine. Furthermore, we discuss the possible role of the brain–gut–microbiota axis and brain–spleen axis in stress-related psychiatric disorders and in the antidepressant-like action of arketamine. Finally, we discuss the potential of arketamine as a treatment for cognitive impairment in psychiatric disorders, Parkinson’s disease, osteoporosis, inflammatory bowel diseases, and stroke.

scholarly journals Medical management of Crohn’s disease: state of the art and future perspectives

2019 ◽  
Vol 13 (3) ◽  
pp. 152-160
Author(s):  
Fabio Salvatore Macaluso
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Molecular Mechanisms ◽  
Oral Route ◽  
New Drugs ◽  
Mediators Of Inflammation ◽  
Bowel Diseases ◽  
Intrinsic Complexity ◽  
Inflammatory Bowel

Over the past decade, the improvement in the understanding of the molecular mechanisms of Crohn’s disease (CD) led to the development of more targeted therapies, including biologics - i.e. monoclonal antibodies that selectively block key mediators of inflammation - and novel small molecule drugs - i.e. compounds with a molecular weight <1 kDa able to diffuse through cell membranes and then fit for the oral route of administration - which will enrich the therapeutic armamentarium of CD soon. In parallel with the expansion of the medical options, the therapeutic targets to be achieved in patients with CD have changed. In particular, we moved from the simple control of symptoms to more ambitious goals which aim to permanently extinguish the inflammation, even the subclinical one. As a consequence, the role of some of the conventional drugs which have been used in CD for several years, such as 5-aminosalicylates and conventional immunosuppressants, is becoming more limited in favor of these new drugs. This profound modification of CD therapy and the intrinsic complexity of the disease are relevant to the point that the management of inflammatory bowel diseases is gradually becoming a subspecialty in the field of gastroenterology or internal medicine.

scholarly journals The Role of Immune Response and Microbiota on Campylobacteriosis

2021 ◽  
Author(s):  
Ying Fu ◽  
Tahrir Alenezi ◽  
Ayidh Almansour ◽  
Hong Wang ◽  
Zhenquan Jia ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Large Body ◽  
Intestinal Microbiome ◽  
Body Of Knowledge ◽  
Slow Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Million cases of campylobacteriosis and complications of post-Campylobacter jejuni infection occur every year around the world with huge life losses and economic burdens of billions of dollars. Few therapy options, such as antibiotics, are available to relieve severe cases of the enteritis. The slow progression on new intervention discovery and application is partially resulted from limited mechanistic understanding on campylobacteriosis pathogenesis. As a type of intestinal disorders, campylobacteriosis shares many common features with other intestinal diseases such as inflammatory bowel diseases (IBD) and Clostridium difficile infection. In pace with the advancement of the gastroenterology field, a large body of knowledge is accumulating on the factors influencing campylobacteriosis onset, development, and outcomes, including host immune response, intestinal microbiota, and its metabolites. In this chapter, we review the intestinal immune system, intestinal microbiome, and microbiome modulation of inflammation in the development of campylobacteriosis. The interplay between immunity, microbiota, and its metabolites may play essential roles on campylobacteriosis pathogenesis and the finding on the interaction may lead to new prevention and treatment options. The purpose of this chapter is to provide updated knowledge on the role of host–microbe interaction and the therapeutic potential on campylobacteriosis.

Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy

2016 ◽  
Vol 34 (1-2) ◽  
pp. 112-121 ◽  
Author(s):  
Richard N. Fedorak ◽  
Kathleen P. Ismond
Keyword(s):  
Ulcerative Colitis ◽  
Gastrointestinal Tract ◽  
Potential Role ◽  
Evidence Base ◽  
Systemic Effect ◽  
Intestinal Microbiome ◽  
Bowel Diseases ◽  
Literature Evidence ◽  
Inflammatory Bowel

The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics, or as an adjunctive therapy to other pharmaceutical treatments. Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract. The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD.

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

Sign in / Sign up

Export Citation Format

Share Document