scholarly journals Effect of Fecal Microbiota Transplantation on Primary Hypertension and the Underlying Mechanism of Gut Microbiome Restoration: Protocol of a Randomized, Double-Blinded, Placebo-Controlled Study

2021 ◽  
Author(s):  
Luyun Fan ◽  
Jie Ren ◽  
Youren Chen ◽  
Yang Wang ◽  
Zihong Guo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Blood Pressure Monitoring ◽  
Fecal Microbiota ◽  
Controlled Study ◽  
Metagenomic Sequencing ◽  
Microbial Composition ◽  
Blood Pressure Elevation ◽  
Double Blinded

Abstract BackgroundHypertension is in current the leading modifiable cause of global morbidity and mortality, contributing to substantial health and financial burdens. Although multiple explorations on management models and innovative therapeutic strategies of hypertension, vacancy still occur in the field with poor control rate reflected and lacking of novel, effectively clinical-translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention on treating hypertension is thus postulated with fecal microbiota transplantation(FMT) from healthy donors performed. MethodsA multi-center, central randomized, placebo-controlled, double-blinded clinical trial is performed in 120 grade 1 hypertensive patients for overall three months. All recruited patients will be randomly assigned in a 1:1 ratio into orally-taken FMT capsules or placebo capsules with three interventions on day 1, day 7 and day 14 in separate, and followed up on day 30, day 60 and day 90. The primary outcome is the change for office systolic blood pressure from baseline to day 30 follow-up. Main secondary outcomes are BP indicators including changes in systolic and diastolic blood pressure from office, home, and 24-hour ambulatory blood pressure monitoring, assessments of ankle-branchial index and pulse wave velocity, profiling of fecal microbial composition and function, profiling of fecal and serum metabolome, changes in levels of blood glucose, blood lipids and body mass index, assessment of adverse events as a measure of safety. DiscussionStretching from our previous research on the role of gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and firstly explores the potential of fecal microbiota transplantation on treating hypertension. Underlying mechanisms particularly on anchoring specific microorganisms or their postbiotics contributing to blood pressure amelioration will also be investigated via multiple approaches such as metagenomic sequencing and metabolomic profiling.Trial registrationClinicalTrials.gov Identifier: NCT04406129, registried on May 28th, 2020, https://clinicaltrials.gov/ct2/show/NCT04406129

scholarly journals 2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S896-S896
Author(s):  
Benoit Levast ◽  
Cécile Batailler ◽  
Cécile Pouderoux ◽  
Lilia Boucihna ◽  
Sébastien Lustig ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Joint Infection ◽  
Surrogate Marker ◽  
Generation Cephalosporin ◽  
Fecal Microbiota ◽  
Metagenomic Sequencing ◽  
Gut Dysbiosis ◽  
Prosthetic Joint ◽  
The Impact

Abstract Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

scholarly journals Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyun Sik Kim ◽  
Tae Woong Whon ◽  
Hojun Sung ◽  
Yun-Seok Jeong ◽  
Eun Sung Jung ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Growth Performance ◽  
Potential Role ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Microbial Composition ◽  
Calf Diarrhea ◽  
The Family ◽  
Enteric Infections

AbstractCalf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance.

scholarly journals Fecal microbiota transplantation brings about bacterial strain displacement in patients with inflammatory bowel diseases

2018 ◽  
Author(s):  
Manli Zou ◽  
Zhuye Jie ◽  
Bota Cui ◽  
Honggang Wang ◽  
Qiang Feng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Bacterial Colonization ◽  
Fecal Microbiota ◽  
Classification Model ◽  
Metagenomic Data ◽  
Metagenomic Sequencing ◽  
Fecal Samples ◽  
Inflammatory Bowel

ABSTRACTFecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has recently been used to treat inflammatory bowel disease (IBD). To elucidate the extent and principles of microbiota engraftment in IBD patients after FMT treatment, we conducted an interventional prospective cohort study. The cohort included two categories of patients: (1) patients with moderate to severe Crohn’s disease (CD) (Harvey-Bradshaw Index ≥ 7, n = 11, and (2) patients with ulcerative colitis (UC) (Montreal classification, S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors) and follow-up visits were performed at baseline, 3 days, one week, and one month after FMT (missing time points included). At each follow-up time point, fecal samples of the participants were collected along with their clinical metadata. For comparative analysis, 10 fecal samples from 10 healthy people were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from 5 individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent natural microbiota shifts during FMT. All fecal samples underwent shotgun metagenomic sequencing.We found that 3 days after FMT, 11 out of 15 recipients were in remission (3 out of 4 UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (AUC > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as the most contributive factors for prediction accuracy.

scholarly journals The effect of Sennoside A on the improvement of lipopolysaccharide -associated encephalopathy through gut microbiota

2021 ◽  
Author(s):  
Suyan Li ◽  
Fenyan Zhang ◽  
Yiguang Lin ◽  
Xiaoli Niu ◽  
Jian Lv ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Flora ◽  
Fecal Microbiota ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Microbial Composition ◽  
Germ Free ◽  
Sd Rats ◽  
Tnf Α

Abstract Background Accumulating evidence suggests that the intestinal flora is involved in many neurodegenerative diseases. Sepsis can lead to severe intestinal flora imbalance and brain dysfunction. In this study, we investigated Sennoside A may relieve lipopolysaccharide(LPS)-associated encephalopathy via its effect on the gut microbiota in rats. Methods Adult male Sprague-Dawley (SD) rats and germ free (GF) rats were used. The ordinary and germ free SD rats were adopted as a LPS-associated encephalopathy model with or without Sennoside A administration. We investigated gut microbiota diversity and structure, conducted electroencephalograms (EEG) and measured the levels of TNF-α, IL-1β and IL-6 in the cortexes of Sprague Dawley (SD) rats with or without Sennoside A administration. Horizontal fecal microbiota transplantation (FMT) and germ-free rats were used to confirm the important roles of gut microbiota in the mitigation of LPS-associated encephalopathy in rats after Sennoside A supplementation. Results We found that Sennoside A treatment markedly improved brain function in septic rats including decreased ratios of abnormal EEG and lowered levels of TNF-α, IL-1β, and IL-6 in the rat cortexes. While the gut microbiota changed in septic SD rats, Sennoside A improved gut microbial composition, which might mediate its brain protective effects in sepsis. Sennoside A also reduced inflammation in the cortexes of septic rats via gut microbiota improvement. In germ-free rats that received lipopolysaccharide(LPS),Sennoside A could not lower the ratios of abnormal EEG, and could not alleviate TNF-α, IL-1β, and IL-6 levels in the rats’ cortexes. FMT lowered the ratios of abnormal EEG and alleviate TNF-α, IL-1β, and IL-6 levels in rats’ cortexes, which confirmed our hypothesis that the effect of Sennoside A on the improvement of LPS-associated encephalopathy through gut microbiota. Conclusion Our data confirm our hypothesis that Sennoside A likely exerts its brain protective effects through gut microbiota alteration.

scholarly journals Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Guo-Feng Zhou ◽  
Yue-Hua Jiang ◽  
Du-Fang Ma ◽  
Yong-Cheng Wang ◽  
Jin-Long Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Gut Microbiota ◽  
Oral Administration ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Compensatory Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
Herbal Formula ◽  
Gut Microbiota Composition

Background. Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. Methods. The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. Results. Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. Conclusions. These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

scholarly journals Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 113 ◽  
Author(s):  
Eunchong Huang ◽  
Shinwon Kang ◽  
Haryung Park ◽  
Soyoung Park ◽  
Yosep Ji ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Psychological Symptoms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Anxiety Level ◽  
Microbiota Composition ◽  
Microbial Composition ◽  
Host Genetics ◽  
Probiotic Strains ◽  
Anxiety Levels

Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut–brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.

scholarly journals Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sergio Serrano-Villar ◽  
Alba Talavera-Rodríguez ◽  
María José Gosalbes ◽  
Nadia Madrid ◽  
José A. Pérez-Molina ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Alpha Diversity ◽  
Antibiotic Use ◽  
Fecal Microbiota ◽  
Controlled Study ◽  
Double Blind Study ◽  
Intestinal Damage ◽  
Double Blind ◽  
Fatty Acid Binding

AbstractChanges in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

scholarly journals Dysbiosis in Functional Bowel Disorders

2018 ◽  
Vol 72 (4) ◽  
pp. 296-306 ◽  
Author(s):  
Paul Enck ◽  
Nazar Mazurak
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Healthy Person ◽  
Fecal Microbiota ◽  
Functional Bowel Disorders ◽  
Microbial Composition ◽  
Bowel Disorders ◽  
Irritable Bowel ◽  
Benign Disorders

Functional bowel disorders (FBD) resemble a group of diseases of the gastrointestinal (GI) tract that are without a clear pathogenesis; the best known is probably the “irritable bowel syndrome” (IBS). Only recently we have been able to explore the role of the gut microbiota in FBD due to progress in microbiological analytic techniques. There are different ways to explore the role of the gut microbiota and its dysbiosis in FBD. Comparison of the microbial composition in a group of patients with FBD, for example, with IBS to a group of healthy volunteers is one way. Studies have shown that the microbiota in FBD is different from that of healthy controls, but the recorded differences are not necessarily specific for FBD, they may also occur in other diseases. Another approach to explore the role of the gut microbiota in FBD is to challenge the existing “flora” with novel bacteria (probiotics) or with nutritional substrates that stimulate bacterial growth (prebiotics). More than 60 such trials including several thousand patients have been performed in IBS. These studies have produced mixed outcome: some probiotics appear to be better than others, and some appear to work only for a part of the IBS symptoms and not for all. An extreme form of this approach is the transfer of an entire microbiota from 1 healthy person to another, called fecal microbiota transplantation. This has rarely been tested in FBD but is not without risk in benign disorders.

scholarly journals Strain Engraftment Competition and Functional Augmentation in a Multi-donor Fecal Microbiota Transplantation Trial for Obesity

2020 ◽  
Author(s):  
Brooke Wilson ◽  
Tommi Vatanen ◽  
Thilini Jayasinghe ◽  
Karen Leong ◽  
José Derraik ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Fecal Microbiota ◽  
Randomised Control Trial ◽  
Metagenomic Sequencing ◽  
Metabolic Potential ◽  
Microbial Dysbiosis ◽  
Shotgun Metagenomic Sequencing ◽  
Level Shifts ◽  
Double Blinded

Abstract Background Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment has not yet been assessed in the context of multiple donors. Methods We conducted a double-blinded randomised control trial of FMT in 42 adolescents with obesity. Participants were randomised to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6-, 12-, and 26-weeks post-treatment were analysed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients’ gut microbiomes. Results Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterised by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardise FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. Conclusion Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harboured diverse microbial species and genes, and were characterised by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. Trial registration The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001351505)

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