Dataset Information

Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia.

ABSTRACT: BACKGROUND:Microbiome studies suggest the presence of an interaction between the human gut microbiome and soil-transmitted helminth. Upon deworming, a complex interaction between the anthelminthic drug, helminths and microbiome composition might occur. To dissect this, we analyse the changes that take place in the gut bacteria profiles in samples from a double blind placebo controlled trial conducted in an area endemic for soil transmitted helminths in Indonesia. METHODS:Either placebo or albendazole were given every three months for a period of one and a half years. Helminth infection was assessed before and at 3 months after the last treatment round. In 150 subjects, the bacteria were profiled using the 454 pyrosequencing. Statistical analysis was performed cross-sectionally at pre-treatment to assess the effect of infection, and at post-treatment to determine the effect of infection and treatment on microbiome composition using the Dirichlet-multinomial regression model. RESULTS:At a phylum level, at pre-treatment, no difference was seen in microbiome composition in terms of relative abundance between helminth-infected and uninfected subjects and at post-treatment, no differences were found in microbiome composition between albendazole and placebo group. However, in subjects who remained infected, there was a significant difference in the microbiome composition of those who had received albendazole and placebo. This difference was largely attributed to alteration of Bacteroidetes. Albendazole was more effective against Ascaris lumbricoides and hookworms but not against Trichuris trichiura, thus in those who remained infected after receiving albendazole, the helminth composition was dominated by T. trichiura. DISCUSSION:We found that overall, albendazole does not affect the microbiome composition. However, there is an interaction between treatment and helminths as in subjects who received albendazole and remained infected there was a significant alteration in Bacteroidetes. This helminth-albendazole interaction needs to be studied further to fully grasp the complexity of the effect of deworming on the microbiome. TRIAL REGISTRATION:ISRCTN Registy, ISRCTN83830814.

SUBMITTER: Martin I

PROVIDER: S-EPMC6084808 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia.

Martin Ivonne I Djuardi Yenny Y Sartono Erliyani E Rosa Bruce A BA Supali Taniawati T Mitreva Makedonka M Houwing-Duistermaat Jeanine J JJ Yazdanbakhsh Maria M

PLoS neglected tropical diseases 20180809 8

<h4>Background</h4>Microbiome studies suggest the presence of an interaction between the human gut microbiome and soil-transmitted helminth. Upon deworming, a complex interaction between the anthelminthic drug, helminths and microbiome composition might occur. To dissect this, we analyse the changes that take place in the gut bacteria profiles in samples from a double blind placebo controlled trial conducted in an area endemic for soil transmitted helminths in Indonesia.<h4>Methods</h4>Either pl ...[more]

PMID: 30091979

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Project description:BackgroundAronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes.ResultsForty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile.ConclusionIn linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions.

Project description:Iron is an essential micronutrient for life. In mammals, dietary iron is absorbed primarily in the small intestine. Currently, the impacts of dietary iron on the taxonomic structure and function of the gut microbiome and reciprocal effects on the animal host are not well understood. Here, we establish a mouse model of low-iron challenge in which intestinal biomarkers and reduced fecal iron reveal iron stress while serum iron and mouse behavioral markers indicate maintenance of iron homeostasis. We show that the diversity of the gut microbiome in conventional C57BL/6 mice changes dramatically during 2 weeks on a low-iron diet. We also show the effects of a low-iron diet on microbiome diversity are long lasting and not easily recovered when iron is returned to the diet. Finally, after optimizing taxon association methods, we show that some bacteria are unable to fully recover after the low-iron challenge and appear to be extirpated from the gut entirely. In particular, operational taxonomic units (OTUs) from the Prevotellaceae and Porphyromonadaceae families and Bacteroidales order are highly sensitive to low-iron conditions, while other seemingly insensitive OTUs recover. These results provide new insights into the iron requirements of gut microbiome members and add to the growing understanding of mammalian iron cycling.IMPORTANCE All cells need iron. Both too much and too little iron lead to diseases and unwanted outcomes. Although the impact of dietary iron on human cells and tissues has been well studied, there is currently a lack of understanding about how different levels of iron influence the abundant and diverse members of the human microbiome. This study develops a well-characterized mouse model for studying low-iron levels and identifies key groups of bacteria that are most affected. We found that the microbiome undergoes large changes when iron is removed from the diet but that many individual bacteria are able to rebound when iron levels are changed back to normal. That said, a select few members, referred to as iron-sensitive bacteria, seem to be lost. This study begins to identify individual members of the mammalian microbiome most affected by changes in dietary iron levels.

Project description:INTRODUCTION:Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents. METHODS AND ANALYSIS:A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ?30?kg/m2] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14?mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat. ETHICS AND DISSEMINATION:Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER:ACTRN12615001351505; Pre-results.

Project description:BACKGROUND:Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome. RESULTS:All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7?days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel "transplantation index" metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs. CONCLUSIONS:Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.

Dataset Information

Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia.

Publications

Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia.

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