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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma

We investigated the role of 3D genome architecture in instructing functional properties of glioblastoma stem cells (GSCs) by generating the highest-resolution 3D genome maps to-date for this cancer. Integration of DNA contact maps with chromatin and transcriptional profiles identified specific mechanisms of gene regulation, including individual physical interactions between regulatory regions and their target genes. Residing in structurally conserved regions in GSCs was CD276, a gene known to play a role in immuno-modulation. We show that, unexpectedly, CD276 is part of a stemness network in GSCs and can be targeted with an antibody-drug conjugate to curb self-renewal, a key stemness property. Our results demonstrate that integrated structural genomics datasets can be employed to rationally identify therapeutic vulnerabilities in self-renewing cells.\n\nSIGNIFICANCEIn adult GBM, GSCs act as therapy-resistant reservoirs to nucleate tumor recurrence. New therapeutic approaches that target these cell populations hold the potential of significantly improving patient care and overall prognosis for this always-lethal cancer. Our work describes new links between 3D genome architecture and stemness properties in GSCs. In particular, through integration of multiple genomics and structural genomics datasets, we found an unexpected connection between immune-related genes and self-renewal programs in GBM. Among these, we show that targeting CD276 with knockdown strategies or specific antibody-drug conjugates achieve suppression of self-renewal. Strategies to target CD276+ cells are currently in clinical trials for solid tumors. Our results indicate that CD276-targeting agents could be deployed in GBM to specifically target GSC populations.\n\nHIGHLIGHTSO_LIWe generated high (sub-5 kb) resolution Hi-C maps for stem-like cells from GBM patients.\nC_LIO_LIIntegration of Hi-C and genomics datasets dissects mechanisms of gene regulation.\nC_LIO_LI3D genomes poise immune-related genes, including CD276, for expression.\nC_LIO_LITargeting CD276 curbs self-renewal properties of GBM cells.\nC_LI

cancer biology↗

bioRxiv2018

Novel Methods for Epistasis Detection in Genome-Wide Association Studies

More and more genome-wide association studies are being designed to uncover the full genetic basis of common diseases. Nonetheless, the resulting loci are often insufficient to fully recover the observed heritability. Epistasis, or gene-gene interaction, is one of many hypotheses put forward to explain this missing heritability. In the present work, we propose epiGWAS, a new approach for epistasis detection that identifies interactions between a target SNP and the rest of the genome. This contrasts with the classical strategy of epistasis detection through exhaustive pairwise SNP testing. We draw inspiration from causal inference in randomized clinical trials, which allows us to take into account linkage disequilibrium. EpiGWAS encompasses several methods, which we compare to state-of-the-art techniques for epistasis detection on simulated and real data. The promising results demonstrate empirically the benefits of EpiGWAS to identify pairwise interactions. Author summaryGenome-wide association studies are now a major tool for the discovery of biomarkers for complex diseases. However, the complexity of genetic architecture, in particular linkage disequilibrium, complicates that mission. Moreover, intergenic interactions, or epistasis, are often not correctly captured by the classical statistical methodologies. In our work, we propose a new framework to model linkage disequilibrium, which is based on propensity scores. Our goal is to detect epistatic interactions between a predetermined target locus and the rest of the genotype. The target may be identified from the literature, experiments, or top hits in previous genome-wide association studies. Recovering interactions with validated causal loci helps improve both interpretability and statistical power. Multi-targeting drug discovery can also benefit from our work through the combination of existing drugs with new ones for greater drug response.

bioinformatics↗

bioRxiv2018

Tissue-specific genes as an underutilized resource in drug discovery

Tissue-specific genes are believed to be good drug targets due to improved safety. Here we show that this intuitive notion is not reflected in phase 1 and 2 clinical trials, despite the historic success of tissue-specific targets and their 2.3-fold overrepresentation among targets of marketed non-oncology drugs. We compare properties of tissue-specific genes and drug targets. We show that tissue-specificity of the target may also be related to efficacy of the drug. The relationship may be indirect (enrichment in Mendelian disease genes) or direct (elevated ability to spread perturbations in human protein-protein interactome for tissue-specifically produced enzymes and secreted proteins). Reduced evolutionary conservation of tissue-specific genes may represent a bottleneck for drug projects, prompting development of novel models with smaller evolutionary gap to humans. We highlight numerous open opportunities to use tissue-specific genes in drug research and hope that the current study will facilitate discovery efforts.

bioinformatics↗

bioRxiv2018

Exploratory and prospective model of stent restenosis after Percutaneous Coronary Intervention using MultivariateGaussian Subspatial Regression

A new statistical analysis methodology, "Multivariate Gaussian Subspatial Regression" (MGSR), has been applied to randomized clinical trial data collected from percutaneous coronary intervention (PCI) patients, which combines the descriptive quality of Factorial Techniques and the predictive power of Gaussian Processes. This model has been built from 3 different quantitative coronary angiographic core-lab measures of the same lesion from 2 separate angiograms (at baseline before PCI, at baseline immediately after PCI and at 12 months follow-up). Measurements of the pre-PCI variables of a patient are mapped to the factorial plane and predictions are visualized as regions of interest in this plane. MGSR makes it possible to detect patients at risk of coronary stent restenosis or patients in whom ruling out the disease, in a graphical way; avoiding unnecessary, costly and possibly risky treatments for patients with no complications predicted; and advising to closely follow patients at risk. In addition, the model recovers missing values regardless of the variables, and once fitted, it corrects itself when more dependent variables are included. MGSR software is freely available online at https://github.com/victorvicpal/MGSR.

bioinformatics↗

bioRxiv2018

Comparative mode of action of antimicrobial peptide melimine and its derivative Mel4 against Pseudomonas aeruginosa

Melimine and Mel4 are chimeric cationic peptides with broad spectrum antimicrobial activity, and recent investigations have shown that they are highly biocompatible with animal model and human clinical trials. The current study examined the mechanism of action of these two antimicrobial peptides against P. aeruginosa with a series of investigations. Antimicrobial activities were determined by MIC and MBC. Endotoxin neutralization was determined using the LAL assay, effect on the cytoplasmic membrane was evaluated using DiSC(3)-5 and Sytox green stains, and Syto-9 and PI dyes using flow cytometry. Release of cytoplasmic materials (ATP and DNA/RNA) were determined using ATP luminescence and increase in OD260nm. The ability to lyse bacteria was studied by measuring a decrease in OD620nm. The MIC of the peptides remained low against P. aeruginosa strains, which showed efficient neutralization of LPS, indicating their role in the anti-pseudomonas and LPS binding activities. Both AMPs rapidly (starting at 30 seconds) depolarized P. aeruginosa cytoplasmic membrane leading to reduction in viability. Melimine was responsible for more ATP release (75%) compared to Mel4 (36%) (P<0.001) following two minutes exposure. For both peptides, Sytox green entered cells after five minutes of incubation. Flow cytometry demonstrated that both the AMPs permeabilized the cell membrane at 30 minutes and followed by increasing permeability. Similar results were found with DNA/RNA release experiments. Overall, melimine showed higher ability of membrane disruption, cell lysis compared to Mel4 (P<0.001). Knowledge regarding mechanism of action of these two AMPs would be helpful in making them as anti-pseudomonas drug.

microbiology↗

bioRxiv2018

Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank

Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we perform the largest genome-wide association study for osteoarthritis to date (77,052 cases and 378,169 controls), analysing 4 phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discover 64 signals, 52 of them novel, more than doubling the number of established disease loci. Six signals fine map to a single variant. We identify putative effector genes by integrating eQTL colocalization, fine-mapping, human rare disease, animal model, and osteoarthritis tissue expression data. We find enrichment for genes underlying monogenic forms of bone development diseases, and for the collagen formation and extracellular matrix organisation biological pathways. Ten of the likely effector genes, including TGFB1, FGF18, CTSK and IL11 have therapeutics approved or in clinical trials, with mechanisms of action supportive of evaluation for efficacy in osteoarthritis.

genetics↗

bioRxiv2017

Protection of the human gut microbiome from antibiotics

BackgroundAntibiotics are life-saving drugs but severely affect the gut microbiome with short term consequences including diarrhoea, Clostridium difficile infections and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.\n\nMethodsWe performed a randomized controlled trial (ClinicalTrials.gov NCT02176005) in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in two parallel groups, with or without DAV132 co-administration. Two control goups of 8 volunteers each receiving DAV132 alone, or a non-active substitute, were added.\n\nResultsThe co-administration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex-vivo.\n\nConclusionsDAV132 was highly effective to protect the gut microbiome of moxifloxacin - treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.

clinical trials↗

bioRxiv2018

Dosage Matters: A Randomized Controlled Trial of Rehabilitation Dose in the Chronic Phase after Stroke

Background and PurposeFor stroke rehabilitation, task-specific training in animal models and human rehabilitation trials is considered important to trigger inherent neuroplasticity, promote motor learning, and functional recovery. Little is known, however, about what constitutes an effective dosage of therapy.\n\nMethodsThis is a parallel group, four arm, single blind, phase I, randomized control trial of four dosages of upper extremity therapy delivered in an outpatient setting during the chronic phase after stroke. Participants were randomized into groups that varied in total dosage of therapy (i.e., 0, 15, 30, or 60 hours). Seven hundred and four participants were assessed for eligibility, 50 were eligible to enroll, 45 were randomized, 44 participated and 41 completed the study. Planned primary analyses used linear mixed effects regression to model baseline to post-intervention changes in the Motor Activity Log-Quality of Movement rating (MALQ) and the Wolf Motor Function Test (WMFT) time score as a function of therapy dosage. A series of hierarchical models were constructed using the MALQ and WMFT.\n\nResultsWe observed a significant dose response curve: the greater the dosage of training, the greater the change in MALQ, with the dose by week slope parameter of 0.0045 ({Delta}MAL/hour/week; p = 0.0011; 95% CI = [0.0019; 0.0071]). Over the 3 weeks of therapy, this corresponds to a gain of 0.81 in MALQ for the 60 hour dose.\n\nConclusionsFor mild-to-moderately impaired stroke survivors, the dosage of a patient-centered, task specific motor therapy was shown to systematically influence the gain in quality of arm use in the natural environment, but not functional capacity as measured in the laboratory. We highlight the importance of recovery outcomes that capture arm use vs. functional capacity.\n\nClinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT 01749358

clinical trials↗

bioRxiv2017

A randomized comparison of different hormone replacement protocols for thawed blastocyst transfer

BackgroundThere are no randomized controlled trials evaluating the pregnancy rates after thawed blastocyst transfers in patients treated with various hormone replacement regimens.\n\nMethodsA prospective randomized controlled trial was conducted to evaluate the outcomes in three different hormone replacement protocols for thawed blastocyst transfer. A total of 330 women (median age 38.2 years) who were undergoing IVF at our clinic were enrolled.\n\nResultsSerum estradiol (E2) levels were 267.71 pg/ml in Premarin group, 391.22 pg/ml in Estrogel group and 495.12 pg/ml in Estrana tape group. Therefore, serum E2 levels in Estrana tape group were higher than those of the other two groups (P<0.01). The pregnancy rate in the Estrogel group was higher than that in the Premarin group (30.0% versus 17.3%, P=0.026, odds ratio 2.05, 95% confidence interval: 1.09-3.87). Furthermore, the pregnancy rate in the Estrana tape group was higher than that in the Estrogel group (43.6% versus 30.0%, P=0.036, odds ratio 1.81, 95% confidence interval: 1.04-3.14).\n\nConclusionThe serum E2 levels contributed to differences observed in the pregnancy rate among the three different protocols. Thus, Estrana tape has an advantage as a hormone replacement protocol for thawed blastocyst transfer.

clinical trials↗

bioRxiv2018

Economic evaluation of a healthy lifestyle intervention for chronic low back pain: a randomised controlled trial

We performed an economic evaluation of a healthy lifestyle intervention targeting weight loss, physical activity and diet for patients with chronic low back pain, who are overweight or obese. Eligible patients with chronic low back pain (n=160) were randomised to an intervention or usual care control group. The intervention included brief advice, a clinical consultation and referral to a 6-month telephone-based healthy lifestyle coaching service. The primary outcome was quality-adjusted life years (QALYs). Secondary outcomes were pain intensity, disability, weight, and body mass index. Costs included intervention costs, healthcare utilisation costs and work absenteeism costs. An economic analysis was performed from the societal perspective. Mean total costs were lower in the intervention group than the control group (-$614; 95%CI: -3133 to 255). The intervention group had significantly lower healthcare costs (-$292; 95%CI: -872 to -33), medication costs (-$30; 95%CI: -65 to -4) and absenteeism costs (-$1000; 95%CI: -3573 to -210). For all outcomes, the intervention was on average less expensive and more effective than usual care, and the probability of the intervention being cost-effective compared to usual care was relatively high (i.e. 0.81) at a willingness-to-pay of $0/unit of effect. However, the probability of cost-effectiveness was not as favourable among sensitivity analyses. The healthy lifestyle intervention seems to be cost-effective from the societal perspective. However, variability in the sensitivity analyses indicates caution is needed when interpreting these findings.

clinical trials↗

bioRxiv2018

Short-term aerobic training does not improve memory functioning in relapsing remitting multiple sclerosis - a randomized controlled trial

BackgroundOnly few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in MS.\n\nObjective and methodsThis randomized controlled trial aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting MS. The primary outcome was verbal memory (Verbal learning and memory test, VLMT). Patients were randomized to an intervention group (IG) program or a waitlist control group (CG). Patients in the IG exercised according to an individually tailored training schedule (with 2-3 sessions per week for 12 weeks). The primary analysis was carried out using the intention-to-treat (ITT) sample with ANCOVA adjusting for baseline scores.\n\nResults77 RRMS patients were screened and 68 participants randomized (CG n=34; IG n=34). The sample comprised 68% females, had a mean age of 39 years, a mean disease duration of 6.3 years, and a mean EDSS of 1.8. No significant effects were detected in the ITT analysis for the primary endpoint VLMT or any other cognitive measures. Moreover, no significant treatment effects were observed for quality of life, fatigue, or depressive symptoms.\n\nConclusionThis study failed to demonstrate beneficial effects of aerobic exercise on cognition in RRMS.\n\nThe trial was prospectively registered at clinicaltrials.gov (NCT02005237).

clinical trials↗

bioRxiv2017

Targeting regulatory T cells with Interleukin-2 treatment in type 1 diabetes: a response-adaptive, non-randomised, open-label trial of repeat doses of Aldesleukin (DILfrequency)

BackgroundType 1 diabetes (T1D) results from loss of immune regulation leading to the development of autoimmunity to pancreatic beta-cells, involving autoreactive T effector cells (Teffs). Regulatory T cells (Tregs), that prevent autoimmunity, require Interleukin-2 (IL-2) for maintenance of immunosuppressive functions and, alterations in the IL-2 pathway predispose to T1D. Using an adaptive trial design we aimed to determine the optimal regimen of aldesleukin (recombinant human IL-2) to physiologically enhance Tregs while limiting expansion of autoreactive Teffs.\n\nMethodsDILfrequency is a single-center, non-randomised, open-label, response-adaptive study of participants aged 18 to 70 years with T1D. The initial learning phase allocated 12 participants to six different predefined dose-frequency regimens. Then, three cohorts of 8 participants were sequentially allocated dose-frequencies, based on repeated interim analyses of all accumulated trial data. The co-primary endpoints were percentage change in Tregs, Teffs and, CD25 ( subunit of the IL-2 receptor) expression by Tregs, from baseline to steady state. Trial registration ISRCTN40319192 and ClinicalTrials.gov (NCT02265809).\n\nFindings115 participants were assessed between November 17th 2014 and May 22nd 2016, 38 participants were enrolled with 36 completing treatment. The optimal regimen to maintain a steady state increase in Tregs of 30% and CD25 expression of 25% without Teff expansion is 0.26 x 106 IU/m2 (95% CI (-0.007 to 0.485)) every 3 days (1.3 to 4.4). Tregs and CD25 were dose-frequency responsive, while Teffs were not. The commonest adverse event was injection site reaction (464/694 events), with a single participant developing transient eosinophilia at the highest dose (0.47 x 106 IU/m2).\n\nInterpretationThis response-adaptive trial defined a well-tolerated aldesleukin regimen that specifically induces Treg expansion that can now be trialled to treat T1D.\n\nFundingSir Jules Thorn Trust, Wellcome, JDRF, SNSF, NIHR

clinical trials↗

bioRxiv2017

A Sign of Disparity: Racial/Ethnic Composition of Treatment Centers is an Independent Risk Factor in SPRINT Trial

The racial composition of treatment centers in the SPRINT trial is an independent risk factor for myocardial infarction (MI) and stroke. Independent of individual race or ethnicity, patients face a 39% increase in relative risk of MI or stroke when associated to treatment centers with a high proportion of African Americans. The magnitude of this effect is comparable to smoking. This suggests the strong influence of social determinants on health outcomes among hypertensive patients.

clinical trials↗

bioRxiv2017

Correction of the Framingham Risk Score Data Reported in SPRINT

This report describes an error in the Framingham Risk Score data presented in the original SPRINT publication.1 The data, presented in Table 1 of the main SPRINT publication in the New England Journal of Medicine and made available to SPRINT Challenge participants, incorrectly calculated the level of baseline cardiovascular risk of the study participants using the Framingham Risk Score. The correct calculation increased the number of participants identified as having >15% 10-year risk from 5737 to 7089, a change from 61% to 76% of the total study population. This information is important for researchers attempting to validate and extend the trials findings and is particularly germane because the recently released American Heart Association/American College of Cardiology blood pressure guidelines changed blood pressure targets for pharmacologic therapy only for high-risk individuals.\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@5ed416org.highwire.dtl.DTLVardef@1b60929org.highwire.dtl.DTLVardef@137409org.highwire.dtl.DTLVardef@127169borg.highwire.dtl.DTLVardef@13d3666_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1C_FLOATNO O_TABLECAPTIONRegression Coefficients for Cox regression model used to predict CVD risk4\n\nC_TABLECAPTION C_TBL

clinical trials↗

bioRxiv2015

A prospective randomized trial examining health care utilization in individuals using multiple smartphone-enabled biosensors

BackgroundMobile health and digital medicine technologies are becoming increasingly used by individuals with common, chronic diseases to monitor their health. Numerous devices, sensors, and apps are available to patients and consumers - some of which have been shown to lead to improved health management and health outcomes. However, no randomized controlled trials have been conducted which examine health care costs, and most have failed to provide study participants with a truly comprehensive monitoring system.\n\nMethodsWe conducted a prospective randomized controlled trial of adults who had submitted a 2012 health insurance claim associated with hypertension, diabetes, and/or cardiac arrhythmia. The intervention involved receipt of one or more mobile devices that corresponded to their condition(s) and an iPhone with linked tracking applications for a period of 6 months; the control group received a standard disease management program. Moreover, intervention study participants received access to an online health management system which provided participants detailed device tracking information over the course of the study. This was a monitoring system designed by leveraging collaborations with device manufacturers, a connected health leader, health care provider, and employee wellness program - making it both unique and inclusive. We hypothesized that health resource utilization with respect to health insurance claims may be influenced by the monitoring intervention. We also examined health-self management.\n\nResults & ConclusionsThere was little evidence of differences in health care costs or utilization as a result of the intervention. Furthermore, we found evidence that the control and intervention groups were equivalent with respect to most health care utilization outcomes. This result suggests there are not large short-term increases or decreases in health care costs or utilization associated with monitoring chronic health conditions using mobile health or digital medicine technologies. Among secondary outcomes there was some evidence of improvement in health self-management which was characterized by a decrease in the propensity to view health status as due to chance factors in the intervention group.\n\nDisclosure of FundingThis research is funded in part by a NIH/NCATS flagship Clinical and Translational Science Award Grant (1UL1 TR001114), Qualcomm Foundation Scripps Health Digital Medicine Research Grant, and Scripps Healths Division of Innovation and Human Capital and Division of Scripps Genomic Medicine. Support for the study is also provided by HealthComp Third Party Administrator, Sanofi, AliveCor, and Accenture.\n\nTrial Registration: clinicaltrials.gov Identifier NCT01975428

Clinical Trials↗

bioRxiv2018

Causal mechanisms of a healthy lifestyle intervention for patients with musculoskeletal pain who are overweight or obese

We assessed the causal mechanisms of a healthy lifestyle intervention for patients with chronic low back pain and knee osteoarthritis (OA), who are overweight or obese. We conducted causal mediation analyses of aggregated data from two RCTs; which included 160 patients with chronic low back pain, and 120 patients with knee OA. Participants were randomised via one central randomisation schedule, to the intervention, or usual care. The intervention consisted of brief advice and referral to a 6-month telephone-based healthy lifestyle coaching service. Participants in the back pain trial were also offered a single physiotherapy consultation. The hypothesised primary mediator was self-reported weight, and alternative mediators were diet, physical activity, and pain beliefs. Outcomes were pain intensity, disability, and quality of life (QoL). Data were analysed using causal mediation analyses with sensitivity analyses for sequential ignorability. All mediation models were specified a priori. The intervention had no effect on pain intensity, disability or physical QoL. The intervention significantly improved mental QoL, however, the intervention effect was not channelled via the selected mediators. The intervention did not reduce weight, or the alternative mediators (diet, physical activity, pain beliefs), and these mediators were not associated with the outcomes (with one exception; poor diet was associated with lower mental QoL). The sensitivity analyses showed that our estimates were stable across all possible levels of residual confounding. Our findings show that the intervention did not cause a meaningful change in the hypothesised mediators, and these mediators were not associated with patient outcomes.

clinical trials↗

bioRxiv2018

Prospective randomized controlled study directly comparing tadalafil and tamsulosin for male patients with lower urinary tract symptoms.

Lower urinary tract symptoms are widespread in elderly men and often suggestive of benign prostatic hyperplasia (LUTS/BPH). A randomized, prospective, and open-labeled trial directly comparing the effects of tadalafil (a phosphodiesterase 5 inhibitor) 5 mg once daily and tamsulosin (an 1-blocker) 0.2 mg once daily for 12 weeks in LUTS/BPH patients was conducted. Data were recorded before randomization as well as at 4, 8, and 12 weeks after medication. Fifteen patients allocated tadalafil and 20 allocated tamsulosin completed 12 weeks of medication. Total IPSS, IPSS voiding, and IPSS-QOL scores declined with medication, but there was no difference between drugs. IPSS storage scores reduced more in the tamsulosin group than tadalafil group. OABSS did not decline significantly with medication. IIEF5 was maintained in the tadalafil group, but declined in the tamsulosin group. The maximum flow rate and post-void residual urine volume did not significantly change with medication. Daytime, night-time, and 24-hour urinary frequencies as well as the mean and largest daytime, night-time, and 24-hour voiding volumes per void did not significantly change with medication. In conclusion, tamsulosin was more effective to reduce storage symptoms than tadalafil. Tadalafil had the advantage of maintaining the erectile function.

clinical trials↗

bioRxiv2017

An interventional Soylent diet increases the Bacteroidetes to Firmicutes ratio in human gut microbiome communities: a randomized controlled trial

Our knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has been shown to have causative effects on microbiome composition, which can have subsequent implications on health. Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving. This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet. Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits, which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units (OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an individuals alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary phase. Among Soylent dieters, we find a significant increase in the ratio of Bacteroidetes to Firmicutes abundance, which is associated with several positive health outcomes, including reduced risks of obesity and intestinal inflammation.

clinical trials↗