scholarly journals Gut Microbiota Manipulation in Foals—Naturopathic Diarrhea Management, or Unsubstantiated Folly?

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1137
Author(s):  
Rachel Goodman-Davis ◽  
Marianna Figurska ◽  
Anna Cywinska
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Evidence Based ◽  
Economic Consequence ◽  
Bacterial Strains ◽  
Antimicrobial Resistance Genes ◽  
Health And Disease ◽  
Pros And Cons

Diarrhea in foals is a problem of significant clinical and economic consequence, and there are good reasons to believe microbiota manipulation can play an important role in its management. However, given the dynamic development of the foal microbiota and its importance in health and disease, any prophylactic or therapeutic efforts to alter its composition should be evidence based. The few clinical trials of probiotic preparations conducted in foals to date show underwhelming evidence of efficacy and a demonstrated potential to aggravate rather than mitigate diarrhea. Furthermore, recent studies have affirmed that variable but universally inadequate quality control of probiotics enables inadvertent administration of toxin-producing or otherwise pathogenic bacterial strains, as well as strains bearing transferrable antimicrobial resistance genes. Consequently, it seems advisable to approach probiotic therapy in particular with caution for the time being. While prebiotics show initial promise, an even greater scarcity of clinical trials makes it impossible to weigh the pros and cons of their use. Advancing technology will surely continue to enable more detailed and accurate mapping of the equine adult and juvenile microbiota and potentially elucidate the complexities of causation in dysbiosis and disease. In the meantime, fecal microbiota transplantation may be an attractive therapeutic shortcut, allowing practitioners to reconstruct a healthy microbiota even without fully understanding its constitution.

Role of autophagy in cancer prevention, development and therapy

2013 ◽  
Vol 55 ◽  
pp. 133-151 ◽  
Author(s):  
G. Vignir Helgason ◽  
Tessa L. Holyoake ◽  
Kevin M. Ryan
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Anticancer Therapy ◽  
Substantial Progress ◽  
Health And Disease ◽  
Made In

Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.

scholarly journals Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0182585 ◽  
Author(s):  
Eli L. Moss ◽  
Shannon B. Falconer ◽  
Ekaterina Tkachenko ◽  
Mingjie Wang ◽  
Hannah Systrom ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Functional Divergence ◽  
Fecal Microbiota ◽  
Immunocompromised Patients ◽  
Bacterial Strains

scholarly journals Power calculations for detecting differences in efficacy of fecal microbiota donors

2020 ◽  
Author(s):  
Scott W. Olesen
Keyword(s):  
Clinical Trials ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Clostridioides Difficile ◽  
Number Of Patients ◽  
Reliable Detection ◽  
Inflammatory Bowel ◽  
Study Designs ◽  
Recommended Therapy ◽  
Human Stool

AbstractFecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of other indications, notably inflammatory bowel disease. The immense variability in human stool, combined with anecdotal reports from FMT studies, have suggested the existence of “donor effects”, in which stool from some FMT donors is more efficacious than stool from other donors. In this study, simulated clinical trials were used to estimate the number of patients that would be required to detect donor effects under a variety of study designs. In most cases, reliable detection of donor effects required more than 100 patients treated with FMT. These results suggest that previous reports of donor effects need to be verified with results from large clinical trials and that patient biomarkers may be the most promising route to robustly identifying donor effects.

scholarly journals Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0251590
Author(s):  
Sandeep Verma ◽  
Sudhir K. Dutta ◽  
Elad Firnberg ◽  
Laila Phillips ◽  
Rakesh Vinayek ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Fecal Microbiota Transplantation ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Metagenomic Sequencing ◽  
Bacterial Strains ◽  
Metagenomic Sequence ◽  
Clostridioides Difficile ◽  
Healthy Donors ◽  
Before And After

Background Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT. Methods Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain. Findings A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT. Interpretation These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

scholarly journals Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation

2020 ◽  
Vol 71 (1) ◽  
pp. 137-148 ◽  
Author(s):  
Zaker I. Schwabkey ◽  
Robert R. Jenq
Keyword(s):  
Clinical Trials ◽  
Cell Transplantation ◽  
Human Body ◽  
Hematopoietic Cell Transplantation ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Proper Selection ◽  
Targeted Interventions

The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.

scholarly journals Microbiota-Orientated Treatments for Major Depression and Schizophrenia

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1024 ◽  
Author(s):  
Guillaume B. Fond ◽  
Jean-Christophe Lagier ◽  
Stéphane Honore ◽  
Christophe Lancon ◽  
Théo Korchia ◽  
...  
Keyword(s):  
Major Depression ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Bacterial Strains ◽  
Metabolic Disturbances ◽  
Human Gut ◽  
Safe Technique ◽  
Illness Outcomes ◽  
New Hypothesis

Background and significance. There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. Method. This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. Results. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics’ impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. Conclusion. Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.

scholarly journals Designing fecal microbiota transplant trials that account for differences in donor stool efficacy

2017 ◽  
Vol 27 (10) ◽  
pp. 2906-2917 ◽  
Author(s):  
Scott W Olesen ◽  
Thomas Gurry ◽  
Eric J Alm
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Statistical Power ◽  
Fecal Microbiota Transplantation ◽  
Optimal Strategies ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Number Of Patients ◽  
Inflammatory Bowel

Fecal microbiota transplantation is a highly effective intervention for patients suffering from recurrent Clostridium difficile, a common hospital-acquired infection. Fecal microbiota transplantation’s success as a therapy for C. difficile has inspired interest in performing clinical trials that experiment with fecal microbiota transplantation as a therapy for other conditions like inflammatory bowel disease, obesity, diabetes, and Parkinson’s disease. Results from clinical trials that use fecal microbiota transplantation to treat inflammatory bowel disease suggest that, for at least one condition beyond C. difficile, most fecal microbiota transplantation donors produce stool that is not efficacious. The optimal strategies for identifying and using efficacious donors have not been investigated. We therefore examined the optimal Bayesian response-adaptive strategy for allocating patients to donors and formulated a computationally tractable myopic heuristic. This heuristic computes the probability that a donor is efficacious by updating prior expectations about the efficacy of fecal microbiota transplantation, the placebo rate, and the fraction of donors that produce efficacious stool. In simulations designed to mimic a recent fecal microbiota transplantation clinical trial, for which traditional power calculations predict [Formula: see text] statistical power, we found that accounting for differences in donor stool efficacy reduced the predicted statistical power to [Formula: see text]. For these simulations, using the heuristic Bayesian allocation strategy more than quadrupled the statistical power to [Formula: see text]. We use the results of similar simulations to make recommendations about the number of patients, the number of donors, and the choice of clinical endpoint that clinical trials should use to optimize their ability to detect if fecal microbiota transplantation is effective for treating a condition.

scholarly journals An omics-based framework for assessing the health risk of antimicrobial resistance genes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
An-Ni Zhang ◽  
Jeffry M. Gaston ◽  
Chengzhen L. Dai ◽  
Shijie Zhao ◽  
Mathilde Poyet ◽  
...  
Keyword(s):  
High Risk ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Fecal Microbiota Transplantation ◽  
Antibiotic Resistance Genes ◽  
Fecal Microbiota ◽  
Clinical Applications ◽  
World Health ◽  
Antimicrobial Resistance Genes ◽  
Health Organization

AbstractAntibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.

scholarly journals 16S rRNA sequencing of samples from universal stool bank donors

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Marina Santiago ◽  
Scott W. Olesen
Keyword(s):  
Microbial Community ◽  
16S Rrna ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
16S Rrna Sequencing ◽  
Clostridioides Difficile ◽  
Rrna Sequencing ◽  
Health And Disease ◽  
Gut Microbial Community ◽  
Stool Bank

Abstract Objectives Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs. Data description 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.

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