scholarly journals Virulent Bacteria as Inflammatory and Immune Co-Factor in Colon Carcinogenesis: Evidence From Two Monozygotic Patients and Validation in CRC Patient and Healthy Cohorts

2021 ◽  
Vol 11 ◽  
Author(s):  
Iradj Sobhani ◽  
Emma Bergsten ◽  
Cecile Charpy ◽  
Mathias Chamaillard ◽  
Denis Mestivier
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Bacterial Species ◽  
Monozygotic Twin ◽  
Fecal Microbiota ◽  
Common Disease ◽  
Novel Approach ◽  
Dna Alterations ◽  
Health And Disease ◽  
Immune Tolerant

Colorectal carcinoma (CRC) is a common disease, the incidence of which is increasing according to Western lifestyle; it remains to have a poor prognosis. Western nutriments are presumed to induce mild inflammation within the colonic mucosa, resulting in the accumulation of DNA alterations in colonocytes through a multistage carcinogenesis process. This suggests that most CRCs are related to the environment. Of interest, fecal microbiota composition has been shown yielding a novel approach regarding how environment changes may impact health and disease. Here, we compare whole shotgun metagenomic gut microbiota of two monozygotic twin sisters, one of whom is suffering from an advance colorectal tumor with a profound disequilibrium of the composition of the gut microbiota due to the overexpression of virulent bacteria such as E. coli, Shigella, and Clostridium species in the colon cancer patient’s feces contrasting with low levels of bacterial species such as Faecalibacterium and Akkermansia usually enriched in the healthy adults’ microbial flora. The disequilibrium in microbiota of the CRC patient’s feces as compared to her monozygotic twin sister is linked to inflammatory and immune cell infiltrates in the patient’s colonic tissue. We speculate on the role of microbiota disequilibrium on the immune-tolerant cell infiltrate within CRCs.

scholarly journals Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Stool Samples ◽  
Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

scholarly journals Metaproteomics Analysis Reveals the Adaptation Process for the Chicken Gut Microbiota

2013 ◽  
Vol 80 (2) ◽  
pp. 478-485 ◽  
Author(s):  
Yue Tang ◽  
Anthony Underwood ◽  
Adriana Gielbert ◽  
Martin J. Woodward ◽  
Liljana Petrovska
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Bacterial Species ◽  
Abundant Species ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Sequencing Analysis ◽  
Content Type ◽  
Chicken Gut Microbiota

ABSTRACTThe animal gastrointestinal tract houses a large microbial community, the gut microbiota, that confers many benefits to its host, such as protection from pathogens and provision of essential metabolites. Metagenomic approaches have defined the chicken fecal microbiota in other studies, but here, we wished to assess the correlation between the metagenome and the bacterial proteome in order to better understand the healthy chicken gut microbiota. Here, we performed high-throughput sequencing of 16S rRNA gene amplicons and metaproteomics analysis of fecal samples to determine microbial gut composition and protein expression. 16 rRNA gene sequencing analysis identifiedClostridiales,Bacteroidaceae, andLactobacillaceaespecies as the most abundant species in the gut. For metaproteomics analysis, peptides were generated by using the Fasp method and subsequently fractionated by strong anion exchanges. Metaproteomics analysis identified 3,673 proteins. Among the most frequently identified proteins, 380 proteins belonged toLactobacillusspp., 155 belonged toClostridiumspp., and 66 belonged toStreptococcusspp. The most frequently identified proteins were heat shock chaperones, including 349 GroEL proteins, from many bacterial species, whereas the most abundant enzymes were pyruvate kinases, as judged by the number of peptides identified per protein (spectral counting). Gene ontology and KEGG pathway analyses revealed the functions and locations of the identified proteins. The findings of both metaproteomics and 16S rRNA sequencing analyses are discussed.

scholarly journals Microbiota and Colorectal Cancer: From Gut to Bedside

2021 ◽  
Vol 12 ◽  
Author(s):  
Miguel Silva ◽  
Valentina Brunner ◽  
Markus Tschurtschenthaler
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Tumour Progression ◽  
Cellular Transformation ◽  
Intestinal Epithelial ◽  
Therapeutic Drugs ◽  
New Findings ◽  
Current Therapies ◽  
Health And Disease

Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host’s gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.

scholarly journals An Oligosaccharide Rich Diet Increases Akkermansia spp. Bacteria in the Equine Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Frederikke Christine Lindenberg ◽  
Ditte Olsen Lützhøft ◽  
Lukasz Krych ◽  
James Fielden ◽  
Witold Kot ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
High Throughput Sequencing ◽  
Post Partum ◽  
Bacterial Species ◽  
Test Group ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Anti Inflammatory ◽  
And Control

Some oligosaccharides induce growth of anti-inflammatory bacterial species and induce regulatory immunity in humans as well as animals. We have shown that the equine gut microbiota and the immune-microbial homeostasis largely stabilize within the first 50 days of life. Furthermore, we have previously established that certain bacterial species in the equine gut correlated with regulatory immunity. Accordingly, we hypothesized that an oligosaccharide rich diet fed to foals during the first 50 days would increase the abundance of bacterial species associated with regulatory immunity, and that this would influence immune responses in the foals. Eight pregnant mares and their foals were fed an oligosaccharide rich diet from 4 weeks before expected parturition until 49 days post-partum. Six mares and foals served as control. Fecal microbiota from mares and foals was characterized using 16S rRNA gene amplicon high throughput sequencing. On Day 49 the test foals had significantly higher abundances of Akkermansia spp. Blood sampled from the foals in the test group on Day 7, 28, and 49 showed non-significant increases in IgA, and decreases in IgG on Day 49. In BALB/cBomTac mice inoculated with gut microbiota from test and control foals we found increased species richness, increased relative abundance of several species identified as potentially anti-inflammatory in horses, which were unclassified Clostridiales, Ruminococcaceae, Ruminococcus, Oscilospira, and Coprococcus. We also found increased il10 expression in the ileum if inoculated with test foal microbiota. We conclude that an oligosaccharide diet fed to foals in the “window of opportunity,” the first 50 days of life, increases the abundance of anti-inflammatory species in the microbiota with potentially anti-inflammatory effects on regulatory immunity.

Humanizing the gut microbiota of mice: Opportunities and challenges

2018 ◽  
Vol 53 (3) ◽  
pp. 244-251 ◽  
Author(s):  
Randi Lundberg
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Model Concept ◽  
Food Component ◽  
Invaluable Tool ◽  
Health And Disease ◽  
Pros And Cons ◽  
Relevant Context ◽  
Immunological Abnormalities

Mouse colonized with human fecal microbiota is an interesting model concept with pros and cons like any other model system. The concept provides an ecologically relevant context to study food component and drug metabolism, and is an invaluable tool for phenotype transfer studies to prove the role of the gut microbiota in health and disease. The major drawbacks are the difficulties with transferring certain components of the human microbiota to the recipient mice, and immunological abnormalities observed in these mice. There seem to be unexplored opportunities for trying to reduce these limitations, but careful evaluation of pros, cons and possible alternatives is still necessary.

scholarly journals Orally Administered Targeted Recombinant Beta-Lactamase Prevents Ampicillin-Induced Selective Pressure on the Gut Microbiota: a Novel Approach to Reducing Antimicrobial Resistance

2004 ◽  
Vol 48 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Jaana Harmoinen ◽  
Silja Mentula ◽  
Matti Heikkilä ◽  
Michel van der Rest ◽  
Päivi J. Rajala-Schultz ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Gut Microbiota ◽  
Intestinal Tract ◽  
Selective Pressure ◽  
Fecal Microbiota ◽  
Beta Lactamase ◽  
Novel Approach ◽  
New Strategy ◽  
Induced Changes

ABSTRACT Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant β-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral β-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.

scholarly journals Contribution of Gut Bacteria to Liver Pathobiology

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Gakuhei Son ◽  
Michael Kremer ◽  
Ian N. Hines
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Tissue Injury ◽  
Gut Bacteria ◽  
First Line ◽  
Ischemic Tissue ◽  
Toxin Exposure ◽  
Broad Array ◽  
Health And Disease ◽  
The Relationship

Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells) to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc.), these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.

Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

Science ◽  
2020 ◽  
pp. eabb5920
Author(s):  
Erez N. Baruch ◽  
Ilan Youngster ◽  
Guy Ben-Betzalel ◽  
Rona Ortenberg ◽  
Adi Lahat ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Fecal Microbiota Transplantation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Complete Response ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Clinical Responses ◽  
Melanoma Patients

The gut microbiome has been shown to influence the response of tumors to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. Here we performed a phase I clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in ten patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. Together, these early findings have important implications for modulating the gut microbiota in cancer treatment.

scholarly journals Strain population structure varies widely across bacterial species and predicts strain colonization in unrelated individuals

2020 ◽  
Author(s):  
Jeremiah J. Faith ◽  
Alice Chen-Liaw ◽  
Varun Aggarwala ◽  
Nadeem O. Kaakoush ◽  
Thomas J. Borody ◽  
...  
Keyword(s):  
Population Structure ◽  
Gut Microbiota ◽  
Population Size ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Small Population ◽  
Bacterial Strains ◽  
Bacterial Genomes ◽  
Population Sizes ◽  
Microbial Strain

SummaryThe population structure of strains within a bacterial species is poorly defined, despite the functional importance of strain variation in the human gut microbiota on health. Here we analyzed >1000 sequenced bacterial strains from the fecal microbiota of 47 individuals from two countries and combined them with >150,000 bacterial genomes from NCBI to quantify the strain population size of different bacterial species, as well as the frequency of finding the same strain colonized in unrelated individuals who had no opportunities for direct microbial strain transmission. Strain population sizes ranged from tens to over one-hundred thousand per species. Prevalent strains in common gut microbiota species with small population sizes were the most likely to be harbored in two or more unrelated individuals. The finite strain population size of certain species creates the opportunity to comprehensively sequence the entirety of these species’ prevalent strains and associate their presence in different individuals with health outcomes.

scholarly journals Microbial Population Changes and Their Relationship with Human Health and Disease

2019 ◽  
Vol 7 (3) ◽  
pp. 68 ◽  
Author(s):  
Ana Álvarez-Mercado ◽  
Miguel Navarro-Oliveros ◽  
Cándido Robles-Sánchez ◽  
Julio Plaza-Díaz ◽  
María Sáez-Lara ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Future Directions ◽  
Alcoholic Fatty Liver ◽  
Targeted Interventions ◽  
Number Of Factors ◽  
Health And Disease ◽  
Inflammatory Bowel

Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.

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