The impact of the host intestinal microbiome on carcinogenesis and the response to chemotherapy

2021 ◽  
Author(s):  
Jaime N Wertman ◽  
Katherine A Dunn ◽  
Ketan Kulkarni
Keyword(s):  
Cancer Treatment ◽  
Intestinal Microbiome ◽  
Relevant Research ◽  
Treatment Target ◽  
Safety And Efficacy ◽  
Microbiome Composition ◽  
Response To Chemotherapy ◽  
Cancer Types ◽  
Inflammatory Bowel ◽  
The Impact

The microbiome consists of all microbes present on and within the human body. An unbalanced, or ‘dysbiotic’ intestinal microbiome is associated with inflammatory bowel disease, diabetes and some cancer types. Drug treatment can alter the intestinal microbiome composition. Additionally, some chemotherapeutics interact with microbiome components, leading to changes in drug safety and/or efficacy. The intestinal microbiome is a modifiable target, using strategies such as antibiotic treatment, fecal microbial transplantation or probiotic administration. Understanding the impact of the microbiome on the safety and efficacy of cancer treatment may result in improved treatment outcome. The present review seeks to summarize relevant research and look to the future of cancer treatment, where the intestinal microbiome is recognized as an actionable treatment target.

scholarly journals The impact of molecular tumor profiling on the design strategies for targeting myeloid leukemia and EGFR/CD44-positive solid tumors

2021 ◽  
Vol 12 ◽  
pp. 375-401
Author(s):  
Nikola Geskovski ◽  
Nadica Matevska-Geshkovska ◽  
Simona Dimchevska Sazdovska ◽  
Marija Glavas Dodov ◽  
Kristina Mladenovska ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Molecular Signatures ◽  
Design Strategies ◽  
Diagnostic Modality ◽  
Safety And Efficacy ◽  
Detection And Diagnosis ◽  
The Impact

Nanomedicine has emerged as a novel cancer treatment and diagnostic modality, whose design constantly evolves towards increasing the safety and efficacy of the chemotherapeutic and diagnostic protocols. Molecular diagnostics, which create a great amount of data related to the unique molecular signatures of each tumor subtype, have emerged as an important tool for detailed profiling of tumors. They provide an opportunity to develop targeting agents for early detection and diagnosis, and to select the most effective combinatorial treatment options. Alongside, the design of the nanoscale carriers needs to cope with novel trends of molecular screening. Also, multiple targeting ligands needed for robust and specific interactions with the targeted cell populations have to be introduced, which should result in substantial improvements in safety and efficacy of the cancer treatment. This article will focus on novel design strategies for nanoscale drug delivery systems, based on the unique molecular signatures of myeloid leukemia and EGFR/CD44-positive solid tumors, and the impact of novel discoveries in molecular tumor profiles on future chemotherapeutic protocols.

scholarly journals The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3749
Author(s):  
David L. Suskind ◽  
Dale Lee ◽  
Young-Mo Kim ◽  
Ghassan Wahbeh ◽  
Namita Singh ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Intestinal Microbiome ◽  
Patient Specific ◽  
Carbohydrate Diet ◽  
Microbiome Composition ◽  
The Impact ◽  
Specific Carbohydrate Diet

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn’s Disease. Methods: 18 patients with mild/moderate CD (PCDAI 15–45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. Results: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. Conclusions: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.

Healthy gut microbiota and long term health

2015 ◽  
Vol 6 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Y. Vandenplas
Keyword(s):  
Immune System ◽  
Intestinal Microbiota ◽  
Research Topic ◽  
Intestinal Microbiome ◽  
Microbiome Composition ◽  
Immune Mediated ◽  
The Impact ◽  
Tremendous Impact ◽  
Postnatal Factors

This review summarises how the composition of the gastro-intestinal microbiota depends on pre- and postnatal factors, and birth itself. The impact of method of delivery, feeding during infancy and medications, such as antibiotics and anti-acid medication, on the composition of the gastro-intestinal microbiota has clearly been shown. However, the duration of the impact of these factors is not well established. The gastro-intestinal microbiome composition is associated with many auto-immune mediated diseases. Although causality has not been obviously demonstrated, there is a strong tendency in this direction. Nevertheless, results of the manipulation of the gastro-intestinal microbiome composition in these conditions are often disappointing. A better understanding on factors determining the longterm composition of the gastro-intestinal microbiome and its health consequences are a priority research topic. A better understanding of the association between the microbiome and the immune system may have a tremendous impact on general health.

scholarly journals The impact of tomato fruits containing multi-walled carbon nanotube residues on human intestinal epithelial cell barrier function and intestinal microbiome composition

Nanoscale ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 3639-3655 ◽  
Author(s):  
Mohamed H. Lahiani ◽  
Sangeeta Khare ◽  
Carl E. Cerniglia ◽  
Ramiz Boy ◽  
Ilia N. Ivanov ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Intestinal Microbiome ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cell ◽  
Tomato Fruits ◽  
Microbiome Composition ◽  
Multi Walled Carbon Nanotube ◽  
The Impact

Residues of Carbon Nanotubes in tomato fruits are too low to show significant impact on epithelial cell barrier and microbiome composition.

scholarly journals How to Face the Advent of SARS-CoV-2 Vaccination in IBD Patients: Another Task for Gastroenterologists

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 248
Author(s):  
Alfredo Papa ◽  
Franco Scaldaferri ◽  
Lorenzo Maria Vetrone ◽  
Matteo Neri ◽  
Antonio Gasbarrini ◽  
...  
Keyword(s):  
Chronic Conditions ◽  
Vaccine Development ◽  
Time Lapse ◽  
Safety And Efficacy ◽  
Factors Associated ◽  
The Past ◽  
The World ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Different Parts

The severity of the COVID-19 pandemic has led to an unprecedented effort to develop vaccines against SARS-CoV-2 infection since this seems to be the most effective strategy to counter the pandemic. In the past weeks, the administration of vaccines has started in different parts of the world sustaining the hype of significantly containing the impact of SARS-CoV-2 infection. However, the rapid time lapse from vaccine development to distribution has raised several concerns on its safety and efficacy. This topic is particularly felt by patients with chronic conditions and immumodulating therapies that could compromise their immune system such as inflammatory bowel disease (IBD). Here, we explore the potential future implications of the SARS-CoV-2 vaccines introduction in the IBD field, touching upon the clinical experience coming from available data on vaccinations against other infections. We also dissect the factors associated with the acceptability of SARS-CoV-2 vaccination, describing the possible strategies that gastroenterologist should adopt to reach the highest rate of vaccinations in IBD patients.

scholarly journals Minor alterations in the intestinal microbiota composition upon Rotavirus infection do not affect susceptibility to DSS colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kedir Hussen Hamza ◽  
Emma Dunér ◽  
Isabel Ulmert ◽  
Armando Arias ◽  
Daniel Sorobetea ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Intestinal Barrier ◽  
Intestinal Microbiome ◽  
Enteric Infection ◽  
Intestinal Integrity ◽  
Dss Colitis ◽  
Causative Factors ◽  
Intestinal Immune System ◽  
Inflammatory Bowel ◽  
The Impact

AbstractViral triggers at the intestinal mucosa can have multiple global effects on intestinal integrity, causing elevated intestinal barrier strength and relative protection from subsequent inflammatory bowel disease (IBD) induction in various models. As viruses can interfere with the intestinal immune system both directly and indirectly through commensal bacteria, cause-effect relationships are difficult to define. Due to the complexity of putatively causative factors, our understanding of such virus-mediated protection is currently very limited. We here set out to better understand the impact that adult enteric infection with rotavirus (RV) might have on the composition of the intestinal microbiome and on the severity of IBD. We found that RV infection neither induced significant long-lasting microbiota community changes in the small or large intestine nor affected the severity of subsequent dextran sulfate sodium-induced colitis. Hence, adult murine RV infection does not exert lasting effects on intestinal homeostasis.

scholarly journals Oral Ferric Maltol Does Not Adversely Affect the Intestinal Microbiome of Patients or Mice, But Ferrous Sulphate Does

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2269
Author(s):  
Awad Mahalhal ◽  
Alessandra Frau ◽  
Michael D. Burkitt ◽  
Umer Z. Ijaz ◽  
Christopher A. Lamb ◽  
...  
Keyword(s):  
Ferrous Sulphate ◽  
Sodium Sulphate ◽  
Intestinal Microbiome ◽  
Dextran Sodium Sulphate ◽  
Principal Coordinates Analysis ◽  
Statistical Inferences ◽  
Principal Coordinates ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Measurable Change

Background and Aims: Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency. Methods: Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above). Results: In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS. Conclusions: This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.

scholarly journals Nanomaterial Complexes Enriched With Natural Compounds Used in Cancer Therapies: A Perspective for Clinical Application

2021 ◽  
Vol 11 ◽  
Author(s):  
María Zenaida Saavedra-Leos ◽  
Euclides Jordan-Alejandre ◽  
César López-Camarillo ◽  
Amaury Pozos-Guillen ◽  
César Leyva-Porras ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Bacterial Infections ◽  
Positive Response ◽  
Natural Compounds ◽  
Molecular Characteristics ◽  
Cancer Therapies ◽  
Cancer Types ◽  
The Impact

Resveratrol and quercetin are natural compounds contained in many foods and beverages. Reports indicate implications for the health of the general population; on the other hand the use of both compounds has interesting results for the treatment of many diseases as cardiovascular affections, diabetes, Alzheimer’s disease, viral and bacterial infections among others. Based on their capacities described as anti-inflammatory, antioxidant, and anti-aging, resveratrol and quercetin showed antiproliferative and anticancer activity specifically in maligned cells. These molecular characteristics trigger the pharmacological repurposing of both compounds and improved its research for treating different cancer types with interesting results at in vitro, in vivo, and clinical trial studies. Meanwhile, the development of different systems of drug release in specific sites as nanomaterials and specifically the nanoparticles, potentiates the personal treatment perspective in conjunct with the actual cancer therapies; regularly invasive and aggressive, the perspective of nanomedicine as higher effective and lower invasive has gained popularity. Knowledge of molecular interactions of resveratrol and quercetin in diseases confirms the evidence of multiple benefits, while the multiple analyses suggested a positive response for the treatment and diagnostics of cancer in different stages, including at metastatic stage. The present work reviews the reports related to the impact of resveratrol and quercetin in cancer treatment and its effects when the antioxidants are encapsulated in different nanoparticle systems, which improve the prospects of cancer treatment.

The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Joerg Ermann ◽  
Mederbek Matmusaev ◽  
Emma Haley ◽  
Clemens Braun ◽  
Felix Jost ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Intestinal Microbiome ◽  
Intestinal Immune System ◽  
Pharmacokinetic Properties ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Human And Mouse

ABSTRACT Background and Aims : Mouse and human data implicates the NOD1 and NOD2 sensors of the intestinal microbiome and the associated signal transduction via the RIPK2 kinase as a potentially key signaling node for the development of Inflammatory Bowel Disease (IBD) and an attractive target for pharmacologic intervention. The TRUC mouse model of IBD has been strongly indicated for evaluating the impact of RIPK2 antagonism on intestinal inflammation based on previous studies with NOD1, NOD2 and RIPK2 knockout mice. Methods. We identified and profiled the BI 706039 molecule as a potent and specific functional inhibitor of both human and mouse RIPK2 and with favorable pharmacokinetic properties. We dosed BI 706039 in the spontaneous TRUC mouse model from aged day 28 through aged day 56. Results : Oral, daily administration of BI 706039 caused dose-responsive and significant improvement in colonic histopathological inflammation, colon weight and terminal levels of protein normalized fecal lipocalin (all p< 0.001). These observations correlated with dose-responsively increasing systemic levels of the BI 706039 compound, splenic molecular target engagement of RIPK2 and modulation of inflammatory genes in the colon. Conclusions : A relatively low oral dose of a potent and selective RIPK2 inhibitor can block the signaling interface between the intestinal microbiome and the intestinal immune system and significantly improve disease associated intestinal inflammation.

scholarly journals The Safety and Tolerability of a Potential Alginate-Based Iron Chelator; Results of A Healthy Participant Study

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 674 ◽  
Author(s):  
Richard Horniblow ◽  
Pritesh Mistry ◽  
Mohammed Quraishi ◽  
Andrew Beggs ◽  
Tom Van de Wiele ◽  
...  
Keyword(s):  
Bacterial Communities ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Food Supplement ◽  
Intestinal Microbiome ◽  
Microbial Dysbiosis ◽  
Daily Ingestion ◽  
Inflammatory Bowel ◽  
Gastro Intestinal Tract ◽  
The Impact

Evidence supporting the ferro-toxic nature of iron in the progression of inflammatory bowel disease (IBD) is becoming well established. A microbial dysbiosis is observed in IBD patients, and intra-luminal colonic-iron is able to support a more pathogenic community of bacteria; whether this is attributed to the development of IBD and how iron could be mediating these microbial changes is still unknown. Dietary fibres are commonly used in pre-biotic supplements to beneficially affect the host by improving the viability of bacterial communities within the colon. Alginates are a class of biopolymers considered as prebiotics due to their fibre-like composition and are able to bind metal cations, in particular, iron. Considering that iron excess is able to negatively alter the microbiome, the use of alginate as a food supplement could be useful in colonic-iron chelation. As such, this first-in-man study aimed to assess whether the use of alginate as a dietary iron chelator was both safe and well tolerated. In addition, the impact of alginate on the microbiome and iron levels was assessed by using an intestinal model SHIME (Simulation of the Human Intestinal Microbial Ecosystem). Alginate was supplemented into the diets (3 g/day) of healthy volunteers (n = 17) for 28 days. Results from this study suggest that daily ingestion of 3 g alginate was well tolerated with very minor side effects. There were no detrimental changes in a variety of haematological parameters or the intestinal microbiome. The bacterial communities within the SHIME model were also not influenced by iron and or alginate; it is possible that alginate may be susceptible to bacterial or enzymatic degradation within the gastro-intestinal tract.

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