scholarly journals The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006132020
Author(s):  
Dominic S. Raj ◽  
Michael B. Sohn ◽  
David M. Charytan ◽  
Jonathan Himmelfarb ◽  
T. Alp Ikizler ◽  
...  
Keyword(s):  
Feasibility Study ◽  
Gut Microbiome ◽  
Post Treatment ◽  
Intestinal Microbiome ◽  
Maintenance Hemodialysis ◽  
Sample Collection ◽  
Microbiome Composition ◽  
Stool Samples ◽  
Pre Treatment ◽  
End Stage

Background: The intestinal microbiome is an appealing target for interventions in end-stage kidney disease (ESKD) because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods: Multi-center, non-randomized, crossover feasibility study of maintenance hemodialysis patients consisting of 3 phases: pre-treatment (8 weeks), treatment during which the prebiotic, p-inulin (Prebiotin®), was administered at a dose of 8 gm twice daily (12 weeks), and post-treatment (8 weeks). Stool samples were collected 1-2 times/week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal RNA sequencing and metabolomic profiling. Results: Eleven of the 13 participants completed the 28-week study. Inter-participant variability was greater than intra-participant variability for microbiome composition (p<0.001 by UniFrac distances), and metabolomic composition (p<0.001 by Euclidean distances). p-Inulin was well-tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pre-treatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (p=0.004) and a progressive decrease in prevalence of high intra-class correlations indicating an increase in intra-participant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions: The intra-participant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.

scholarly journals HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

2019 ◽  
Author(s):  
Mark Asquith ◽  
Peter R. Sternes ◽  
Mary-Ellen Costello ◽  
Lisa Karstens ◽  
Sarah Diamond ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Marker Gene ◽  
Intestinal Microbiome ◽  
Hla B27 ◽  
Microbial Composition ◽  
Hla Alleles ◽  
Microbiome Composition ◽  
Stool Samples

ABSTRACTObjectivesHLA alleles affect susceptibility to more than 100 diseases, but the mechanisms to account for these genotype-disease associations are largely unknown. HLA-alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and faecal microbiome signatures. Whether these changes are cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examine the effect ofHLA-B27andHLA-DRB1RA-risk alleles on the composition of the intestinal microbiome in healthy individuals.Methods568 samples from 6 intestinal sites were collected from 107 otherwise healthy unrelated subjects and stool samples from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S rRNA bacterial marker gene. All patients were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data.ResultsAssociation was observed betweenHLA-B27genotype, and RA-riskHLA-DRB1alleles, and overall microbial composition (P=0.0002 and P=0.00001 respectively). These associations were replicated in the TwinsUK cohort stool samples (P=0.023 and P=0.033 respectively).ConclusionsThis study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects ofHLA-B27and –DRB1on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome, and suggest that therapies targeting the microbiome may be effective in their prevention and/or treatment.

scholarly journals Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1874 ◽  
Author(s):  
Angela Horvath ◽  
Marija Durdevic ◽  
Bettina Leber ◽  
Katharina di Vora ◽  
Florian Rainer ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Controlled Trial ◽  
16S Rrna Gene Sequencing ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Microbiome Composition ◽  
Beneficial Effects ◽  
Compensated Cirrhosis ◽  
Gut Barrier Function ◽  
Probiotic Treatment

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.

scholarly journals Effect of long-term methylene blue treatment on the composition of mouse gut microbiome and its relationship with the cognitive abilities of mice

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241784
Author(s):  
Artem P. Gureev ◽  
Mikhail Yu. Syromyatnikov ◽  
Daria A. Ignatyeva ◽  
Valeria V. Valuyskikh ◽  
Sergey A. Solodskikh ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Gut Microbiome ◽  
Cognitive Abilities ◽  
Antibacterial Properties ◽  
Intestinal Microbiome ◽  
Control Group ◽  
High Concentration ◽  
Microbiome Composition ◽  
Gut Dysfunction ◽  
Taxonomic Groups

In recent years, methylene blue (MB) has attracted considerable interest as a potential drug for the treatment of methemoglobinemia and neurodegenerative diseases. MB is active against microorganisms from various taxonomic groups. However, no studies have yet been conducted on the effect of MB on the intestinal microbiome of model animals. The aim of this work was to study the effect of different concentrations of MB on the mouse gut microbiome and its relationship with the cognitive abilities of mice. We showed that a low MB concentration (15 mg/kg/day) did not cause significant changes in the microbiome composition. The Bacteroidetes/Firmicutes ratio decreased relative to the control on the 2nd and 3rd weeks. A slight decrease in the levels Actinobacteria was detected on the 3rd week of the experiment. Changes in the content of Delta, Gamma, and Epsilonproteobacteria have been also observed. We did not find significant alterations in the composition of intestinal microbiome, which could be an indication of the development of dysbiosis or other gut dysfunction. At the same time, a high concentration of MB (50 mg/kg/day) led to pronounced changes, primarily an increase in the levels of Delta, Gamma and Epsilonproteobacteria. Over 4 weeks of therapy, the treatment with high MB concentration has led to an increase in the median content of Proteobacteria to 7.49% vs. 1.61% in the control group. Finally, we found that MB at a concentration of 15 mg/kg/day improved the cognitive abilities of mice, while negative correlation between the content of Deferribacteres and cognitive parameters was revealed. Our data expand the understanding of the relationship between MB, cognitive abilities, and gut microbiome in respect to the antibacterial properties of MB.

scholarly journals Alterations in gut microbiome composition and function in irritable bowel syndrome and increased probiotic abundance with daily supplementation

2021 ◽  
Author(s):  
Joann Phan ◽  
Divya Nair ◽  
Suneer Jain ◽  
Thibaut Montagne ◽  
Demi Valeria Flores ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiome ◽  
The United States ◽  
Supporting Evidence ◽  
Metagenomic Sequencing ◽  
Healthy Controls ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Stool Samples ◽  
Irritable Bowel

AbstractBackgroundIrritable bowel syndrome (IBS) is characterized by abdominal discomfort and irregular bowel movements and stool consistency. Because there are different symptoms associated with IBS, it is difficult to diagnose the role of the microbiome in IBS.ObjectiveHere, we present a study that includes metagenomic sequencing of stool samples from subjects with the predominant subtypes of IBS and a healthy cohort. We collected longitudinal samples from individuals with IBS who took daily made-to-order precision probiotic and prebiotic supplementation throughout the study.Materials and MethodsThis study includes a population of 489 individuals with IBS and 122 healthy controls. All stool samples were subjected to shotgun metagenomic sequencing. Precision probiotics and prebiotics were formulated for all subjects with longitudinal timepoints.ResultsThere was significant variation explained in the microbiome between the healthy and IBS cohorts. Individuals with IBS had a lower gut microbiome diversity and reduced anti-inflammatory microbes compared to the healthy controls. Eubacterium rectale and Faecalibacterium prausnitzii were associated with healthy microbiomes while Shigella species were associated with IBS. Pathway analysis indicated a functional imbalance of short chain fatty acids, vitamins, and a microbial component of Gram-negative bacteria in IBS compared to healthy controls. In the longitudinal dataset, there was a significant difference in microbiome composition between timepoints 1 and 3. There was also a significant increase in the overall microbiome score and relative abundances of probiotic species used to target the symptoms associated with IBS.ConclusionsWe identified microbes and pathways that differentiate healthy and IBS microbiomes. In response to precision probiotic supplementation, we identified a significant improvement in the overall microbiome score in individuals with IBS. These results suggest an important role for probiotics in managing IBS symptoms and modulation of the microbiome as a potential management strategy.ImportanceAn estimated 35 million people in the United States and 11.5% of the population globally are affected by IBS. Immunity, genetics, environment, diet, small intestinal bacterial overgrowth (SIBO), and the gut microbiome are all factors that contribute to the onset or triggers of IBS. With strong supporting evidence that the gut microbiome may influence symptoms associated with IBS, elucidating the important microbes that contribute to the symptoms and severity is important to make decisions for targeted treatment. As probiotics have become more common in treating IBS symptoms, identifying effective probiotics may help inform future studies and treatment.

scholarly journals The Microbiota Diversity Following Antibiotic Treatment of Clostridium Difficile Infection

2020 ◽  
Author(s):  
Dana Binyamin ◽  
Orna Nitzan ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Omry Koren ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Gut Microbiome ◽  
Diarrheal Disease ◽  
Medical Center ◽  
Disease Onset ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Stool Samples

Abstract Background: Clostridium difficile (C. difficile) is a major nosocomial pathogen that infects the human gut and can cause diarrheal disease. A dominant risk factor is antibiotic treatment that disrupts the normal gut microbiota. The aim of the study was to examine the correlation between antibiotic treatment received prior to C. difficile infection (CDI) onset and patient gut microbiota.Methods: Stool samples were collected from patients with CDI, presenting at the Baruch Padeh Medical Center Poriya, Israel. Demographic and clinical information, including previous antibiotic treatments, was collected from patient charts, and CDI severity score was calculated. Bacteria were isolated from stool samples, and gut microbiome was analyzed by sequencing the 16S rRNA gene using the Illumina MiSeq platform and QIIME2.Results: In total, 84 patients with C. difficile infection were enrolled in the study; all had received antibiotics prior to disease onset. Due to comorbidities, 46 patients (55%) had received more than one class of antibiotics. The most common class of antibiotics used was cephalosporins (n=44 cases). The intestinal microbiota of the patients was not uniform. Differences in intestinal microbiome were influenced by the different combinations of antibiotics that the patients had received (p = 0.022)Conclusions: The number of different antibiotics administered has a major impact on the CDI patients gut microbiome, mainly on bacterial richness.

scholarly journals Microbiota diversity following antibiotic treatment of Clostridium difficile infection

2020 ◽  
Author(s):  
Dana Binyamin ◽  
Orna Nitzan ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Omry Koren ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Gut Microbiome ◽  
Diarrheal Disease ◽  
Medical Center ◽  
Disease Onset ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Stool Samples

Abstract Background: Clostridium difficile (C. difficile) is a major nosocomial pathogen that infects the human gut and can cause C. difficile infection (CDI), a diarrheal disease. A dominant risk factor is antibiotic treatment, which disrupts the normal gut microbiota. The aim of the study was to examine the correlation between antibiotic treatment received prior to CDI onset and patient gut microbiota during the infection.Methods: Stool samples were collected from patients with CDI, presenting at the Baruch Padeh Medical Center Poriya, Israel. Demographic and clinical information, including previous antibiotic treatments, was collected from patient charts, and CDI severity score was calculated. Bacteria were isolated from stool samples, and gut microbiome was analyzed by sequencing the 16S rRNA gene, using the Illumina MiSeq platform and QIIME2.Results: In total, 84 patients with CDI were enrolled in the study; all had received antibiotics prior to disease onset. Due to comorbidities, 46 patients (55%) received more than one class of antibiotics. The most common class of antibiotics used was cephalosporins (n=44 cases). The intestinal microbiota of the patients was not uniform. Differences in intestinal microbiome were influenced by the different numbers of antibiotics families that the patients received (p = 0.022)Conclusions: The number of different antibiotics amount has a major impact on the gut microbiome of CDI patients, particularly on its bacterial richness.

scholarly journals 2365. Volatile Metabolite-Based Detection of Clostridium difficile Infection (CDI)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S815-S815
Author(s):  
Obadah Aloum ◽  
Mahesh J Thalavitiya Acharige ◽  
Nour Ismail ◽  
Mohamad Hejazi ◽  
Mohamad Al Kateb ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Tertiary Care ◽  
Metabolite Profile ◽  
Serum Lactate ◽  
Intestinal Microbiome ◽  
Care Hospital ◽  
Sample Collection ◽  
Volatile Metabolite ◽  
Volatile Metabolites ◽  
Stool Samples

Abstract Background CDI is a frequent cause of morbidity and mortality in hospitalized patients. Despite advances in rapid CDI testing, there are often delays between the onset of symptoms and receipt of test results. We sought to test the hypothesis that the altered CDI intestinal microbiome has a unique volatile metabolite profile, distinct from the profile of patients with other causes of antibiotic-associated diarrhea, which potentially can be used to identify patients with CDI. Methods We prospectively collected fresh stool samples from inpatients with suspected CDI at an academic tertiary care hospital from July 2015 to November 2017, adsorbed volatile metabolites from each sample onto sorbent tubes within an hour of sample collection, and used thermal desorption-gas chromatography/tandem mass spectrometry to identify each metabolite. All patients were exposed to at least one antibiotic agent in the prior 90 days, and only patients receiving empiric CDI treatment or with formed stool samples were excluded. We used logistic regression models, adjusting for prior anti-anaerobic antibiotic therapy and CDI severity (serum albumin <3 g/dL and WBC ≥ 15,000/mm3 or abdominal tenderness) and adjusting for multiple testing using Storey’s q-value procedure (with a threshold of q ≤ 0.05), to examine the relationship between CDI, as determined by the reference standard of the cell culture cytotoxicity neutralization assay, and each metabolite. Results In our 565-patient cohort, median age was 61 years (IQR 50, 70) and 277 (49%) were male; 173 (31%) had abdominal pain in the 24 hours before testing, 59 (10%) had fevers in the prior 24 hours, 22 (4%) had an ileus, 74 (13%) had mental status changes in the prior 24 hours, 89 (16%) were hospitalized in the ICU at the time of testing, 45 (7%) were receiving pressors, 82 (15%) had a WBC ≥ 15,000/mm3, and 137 (24%) had a serum lactate > 1.5 mmol/L. Ultimately, 155 patients were diagnosed with CDI. Ten metabolites (Table 1, Figure 1) were differentially distributed in patients with and without CDI. Conclusion We identified a suite of volatile metabolites that differentiates stool from patients with and without CDI; this profile may ultimately be used to identify patients with CDI. Disclosures All authors: No reported disclosures.

scholarly journals Patient attitudes towards faecal sampling for gut microbiome studies and clinical care reveal positive engagement and room for improvement

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249405
Author(s):  
Laura A. Bolte ◽  
Marjolein A. Y. Klaassen ◽  
Valerie Collij ◽  
Arnau Vich Vila ◽  
Jingyuan Fu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Faecal Sample ◽  
Clinical Care ◽  
Clinical Applications ◽  
Willingness To Participate ◽  
Sample Collection ◽  
General Population Cohort ◽  
Microbiome Research ◽  
Stool Samples ◽  
Sampling Procedures

Faecal sample collection is crucial for gut microbiome research and its clinical applications. However, while patients and healthy volunteers are routinely asked to provide stool samples, their attitudes towards sampling remain largely unknown. Here, we investigate the attitudes of 780 Dutch patients, including participants in a large Inflammatory Bowel Disease (IBD) gut microbiome cohort and population controls, in order to identify barriers to sample collection and provide recommendations for gut microbiome researchers and clinicians. We sent questionnaires to 660 IBD patients and 112 patients with other disorders who had previously been approached to participate in gut microbiome studies. We also conducted 478 brief interviews with participants in our general population cohort who had collected stool samples. Statistical analysis of the data was performed using R. 97.4% of respondents reported that they had willingly participated in stool sample collection for gut microbiome research, and most respondents (82.9%) and interviewees (95.6%) indicated willingness to participate again, with their motivations for participating being mainly altruistic (57.0%). Responses indicated that storing stool samples in the home freezer for a prolonged time was the main barrier to participation (52.6%), but clear explanations of the sampling procedures and their purpose increased participant willingness to collect and freeze samples (P = 0.046, P = 0.003). To account for participant concerns, gut microbiome researchers establishing cohorts and clinicians trying new faecal tests should provide clear instructions, explain the rationale behind their protocol, consider providing a small freezer and inform patients about study outcomes. By assessing the attitudes, motives and barriers surrounding participation in faecal sample collection, we provide important information that will contribute to the success of gut microbiome research and its near-future clinical applications.

scholarly journals Accelerating Gut Microbiome Research with Robust Sample Collection

2021 ◽  
Author(s):  
Zoe J. Zreloff ◽  
Danielle Lange ◽  
Suzanne D. Vernon ◽  
Martha R. Carlin ◽  
Raul de Jesus Cano
Keyword(s):  
Microbial Diversity ◽  
Stool Sample ◽  
Gut Microbiome ◽  
Critical Role ◽  
Sample Collection ◽  
Fresh Sample ◽  
Microbiome Composition ◽  
Microbiome Profile ◽  
Health And Disease ◽  
Diversity Profiles

Background. Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods. We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bi-oinformatic analyses were used to examine the microbiome composition. Results. The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also re-sulted in varying microbiome profiles. Homogenization and stabilization at 4&deg;C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely be-cause of the freeze/thaw. Conclusions. The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization, and stabilization at 4&deg;C for 24 hours provides a &ldquo;neat&rdquo;, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease.

scholarly journals The Mammalian Intestinal Microbiome: Composition, Interaction with the Immune System, Significance for Vaccine Efficacy, and Potential for Disease Therapy

Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 57 ◽  
Author(s):  
Ulrich Desselberger
Keyword(s):  
Immune Responses ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Gut Bacteria ◽  
Intestinal Microbiome ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Disease Therapy ◽  
Intestinal Pathogens ◽  
The Relationship

The mammalian gut is colonized by a large variety of microbes, collectively termed ‘the microbiome’. The gut microbiome undergoes rapid changes during the first few years of life and is highly variable in adulthood depending on various factors. With the gut being the largest organ of immune responses, the composition of the microbiome of the gut has been found to be correlated with qualitative and quantitative differences of mucosal and systemic immune responses. Animal models have been very useful to unravel the relationship between gut microbiome and immune responses and for the understanding of variations of immune responses to vaccination in different childhood populations. However, the molecular mechanisms underlying optimal immune responses to infection or vaccination are not fully understood. The gut virome and gut bacteria can interact, with bacteria facilitating viral infectivity by different mechanisms. Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).

Sign in / Sign up

Export Citation Format

Share Document