medRxiv最新文献

{"title":"Adult renal tubular organoids can be produced from different human individuals in a completely same protocol","authors":"M. Mori, Y. Mori, Nakao Yuki, Shintaro Mandai, T. Fujiki, Hiroaki Kikuchi, Fumiaki Ando, K. Susa, Takayasu Mori, Y. Waseda, S. Yoshida, Y. Fujii, E. Sohara, Shinichi Uchida","doi":"10.1101/2024.08.11.24311846","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311846","url":null,"abstract":"Introduction: Organoids are miniature organs produced by newly emerging technologies. Kidney organoids originated from human inducible pluripotent stem cells (iPSCs) were developed to recapitulate renal diseases. However, producing iPSC kidney organoids from multiple individuals at the same time and in a uniform condition is still impossible. Here, we report adult renal tubular organoids, \"tubuloids\", established from primary renal epithelial cells from multiple human individuals in a uniform manner. Methods: Kidneys obtained from patients due to the surgery for malignancy were minced into small pieces, and primary renal epithelial tubule cells are cultured. 4 patients had normal kidney function and 4 had mild chronic kidney disease (CKD). Growth factors were added to the primary cultured cells at the same time and Matrigel was added to these 8 lines. Results: Primary cultured renal epithelial cells from normal kidneys showed a large number of fine, swollen epithelial appearance. On the other hand, primary cultured kidney epithelial cells from mild CKD kidneys were smaller and slightly elongated than those of normal kidneys. The growth speed was faster in normal kidney cells than in mild CKD cells. At the beginning of the three-dimensionalization (day 0), normal renal tubuloids grew faster than mild CKD tubuloids. The difference in size between normal tubuloids and mild CKD ones became less noticeable on day 5. Both types of tubuloids reached almost same size on day 10. All 8 strains are of different human origin, and uniform tubuloids could be produced at the same time and in a uniform protocol. Conclusion: In terms of pathological models, the differences between mouse models and humans cannot be ignored, and there is a great need for a more human-like model of human pathology from both medical and research perspectives. Our renal tubular organoids can be produced in a uniform manner at the same time. It is expected to be used as a new type of convenient human pathological model.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"11 35","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying the impact of a broadly protective sarbecovirus vaccine in a future SARS-X pandemic","authors":"Charles Whittaker, Gregory Barnsley, D. Mesa, D. Laydon, Chee Wah Tan, Feng Zhu, Rob Johnson, P. Doohan, G. Nedjati-Gilani, P. Winskill, Alexandra B. Hogan, A. Deol, Christinah Mukandavire, Katharina Hauck, David Chien, Boon Lye, Lin-Fa Wang, Oliver J Watson, Azra C Ghani","doi":"10.1101/2024.08.12.24311730","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311730","url":null,"abstract":"COVID-19 has underscored the need for more timely access to vaccines during future pandemics. This has motivated development of broad-spectrum vaccines providing protection against viral families, which could be stockpiled ahead of an outbreak and deployed rapidly following detection. We use mathematical modelling to evaluate the utility of a broadly protective sarbecovirus vaccine (BPSV) during a hypothetical SARS-X outbreak, including ring-vaccination, spatial targeting and mass vaccination of high-risk populations. Our results show BPSV ring- or spatially-targeted vaccination strategies are unlikely to contain a SARS-CoV-2-like virus but could contain or slow the spread of a SARS-CoV-1-like virus. Vaccination of high-risk populations with the BPSV ahead of a virus-specific vaccine (VSV) becoming available could substantially reduce mortality. For a 250-day VSV development timeline, BPSV availability reduced infection-related deaths in our model by 54% on average, though exact impact depended on the non-pharmaceutical intervention (NPI) scenario considered. We further show that BPSV availability enables shorter and less stringent NPIs to be imposed whilst limiting disease burden to that observed in the VSV-only scenario, though results are sensitive to vaccine properties (e.g. efficacy), health system capabilities (e.g. vaccination rollout speed) and the assumed timeline to VSV availability. Our modelling suggests that availability of a BPSV for those aged 60+ years could have averted 40-65% of COVID-19 deaths during the pandemic's first year, though exact impact depends on the size of the maintained stockpile. Our work highlights significant potential impact of a BPSV, but that achieving this impact depends on investment into health systems enabling rapid and equitable access during future SARS-X pandemics.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"41 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating feature importance techniques and causal inference to enhance early detection of heart disease","authors":"A. Arzanipour","doi":"10.1101/2024.08.11.24311833","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311833","url":null,"abstract":"Heart disease remains a leading cause of mortality worldwide, necessitating robust methods for its early detection and intervention. This study employs a comprehensive approach to identify and analyze critical features contributing to heart disease. Using a dataset of 270 patients, three well-known feature importance techniques--Boruta, Information Gain, and Lasso Regression--are applied to determine the top five features for heart disease detection. Following the identification of these key features, the g-computation method, a causal inference technique, is utilized to explore the causal relationships between these features and the presence of heart disease. The findings provide valuable insights into not only the features that are highly correlated with chronic heart disease but also those that have a direct causal impact on the classification of patients. This integrated approach enhances the understanding of heart disease etiology and can inform more effective diagnostic and therapeutic strategies.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating feature importance techniques and causal inference to enhance early detection of heart disease","authors":"A. Arzanipour","doi":"10.1101/2024.08.11.24311833","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311833","url":null,"abstract":"Heart disease remains a leading cause of mortality worldwide, necessitating robust methods for its early detection and intervention. This study employs a comprehensive approach to identify and analyze critical features contributing to heart disease. Using a dataset of 270 patients, three well-known feature importance techniques--Boruta, Information Gain, and Lasso Regression--are applied to determine the top five features for heart disease detection. Following the identification of these key features, the g-computation method, a causal inference technique, is utilized to explore the causal relationships between these features and the presence of heart disease. The findings provide valuable insights into not only the features that are highly correlated with chronic heart disease but also those that have a direct causal impact on the classification of patients. This integrated approach enhances the understanding of heart disease etiology and can inform more effective diagnostic and therapeutic strategies.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"20 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors determining hemoglobin levels in vaginally delivered term newborns at public hospitals in Lusaka, Zambia","authors":"Adenike Oluwakemi, PhD. Ogah. PhD, Dr Chrispin Mwando, Dr Kenneth Chanda, Dr Selia Nganjo","doi":"10.1101/2024.08.11.24311826","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311826","url":null,"abstract":"Background Limited data is available regarding the prevalence of neonatal anemia and its associated risk factors in areas with constrained resources. Subject and methods In a cross-sectional study, data pertaining to socio-demographic and clinical characteristics of 489 mother-singleton, term newborn pairs were consecutively collected from the admission wards of six public hospitals in Lusaka. The information was then analyzed to determine the prevalence of newborn anemia and its associated risk factors. Newborn and maternal anemia were defined as hemoglobin levels below 15g/dl and 11g/dl, respectively. The relationship between the variables was explored using Chi-square tests and a binary logistic regression model. The findings were reported in terms of p-values, odds ratios, and 95% confidence intervals. Results The prevalence of anemia and severe anemia in newborns was 72.4% and 2.5% respectively, while in mothers it was 30.5% and 14.7% respectively. Delayed cord clamping was performed in 71.4% of the deliveries, and 86.5% of newborns had their hemoglobin levels estimated between 4-6 hours after birth. Maternal pre-delivery hemoglobin data were obtained from the hospital records of 246 (49.7%) out of the 489 mothers in the study. The majority (63.4%) of maternal hemoglobin levels were determined more than 4 weeks before delivery, and this infrequent hemoglobin assessment was significantly associated with newborn anemia (p<0.001; OR 3.60; 95% CI 1.81, 7.14). Additionally, 11% of the 489 mothers had underlying medical conditions, which were also significantly associated with newborn anemia (p=0.019; OR=2.96; [95%CI 1.20, 7.32]). The top three maternal medical conditions were HIV (35.2%), hypertension (25.9%), and Hepatitis B virus infection (13%). Maternal age was significantly associated with newborn anemia, with teenage pregnancy posing the highest risk (93.8%; p<0.001; OR 5.68; [95%CI 1.94, 16.60]). Furthermore, primiparous (p<0.001; OR 5.46 [95% CI 2.02, 14.93]), para 2 (p=0.014; OR=2.11 [95% CI 1.16, 3.83]), and multiparous (p=0.009; OR=4.77; [95% CI 1.48, 15.35]) mothers were more likely to produce anemic newborns compared to other parity. Newborns born before 40 weeks gestation were 3.11 times (95% CI 1.75, 5.52) more likely to have anemia, p<0.001, compared to full-term babies. Normal birthweight babies were less likely to become anemic compared to low birthweight babies (p=0.003; OR=0.31 [95% CI 0.14, 0.68]). Conclusion Enhanced antenatal care for pregnant mothers in resource-limited settings is essential, with particular focus on maternal hemoglobin, nutrition, and medical conditions. Attention should also be given to teenage pregnancy, primiparous and multiparous mothers, as well as preterm and low birthweight babies, to prevent newborn anemia and consequently reduce infant morbidity and mortality.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"8 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate and cost-efficient whole genome sequencing of hepatitis B virus using Nanopore","authors":"Joakim B. Stenbäck, Daniel Schmidt, Ulrika Noborg, Joel Gustafsson, Peter Norberg, Maria E Andersson, Michael X Fu, Heli Harvala, Johan Ringlander","doi":"10.1101/2024.08.12.24311345","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311345","url":null,"abstract":"Deep sequencing of the whole hepatitis B virus genome increases the analytical resolution and has the potential to improve molecular epidemiology investigations. The aim of this work was to develop and evaluate the performance of such deep sequencing using the Nanopore technology. The method includes an initial PCR step to generate two overlapping amplicons that cover the whole HBV genome, followed by sequencing using the Nanopore rapid barcoding kit that allows parallel analysis of several samples in one reaction. The libraries can be sequenced with the standard Nanopore flow cell on MiniIon or GridIon devices, as well as the Flongle. The performance of the method was evaluated by comparing Nanopore and Sanger sequences or qPCR results from 64 clinical samples. The Nanopore-derived consensus sequences were, on average, 99.9% similar to those from Sanger sequencing and the full HBV genome was determined in samples with HBV DNA levels of approximately 3 log10 IU/mL with MagNA pure 96 extraction and < 2 log10 IU/mL using a high-volume manual extraction protocol on a subset of samples from patients with very low viral load (1.62-3.74 IU/mL). A perfect agreement with Sanger/qPCR-derived genotype was seen. The cost of sequencing per genome using the Nanopore method is low, ranging of 6-37 euros. We conclude that whole-genome sequencing of HBV with Nanopore is well suited for genomic characterization, antiviral resistance mutation analysis and genotyping of HBV in a routine laboratory setting","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"8 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal Parasites among Primary School Children in Aden, Yemen","authors":"Ali N. M. Gubran¹ Naif, Mohammed Al-Haidary², Marwa Faisal, M. Bajubair³, Afrah Mohsen, Ali Algibary³, Manal Galeb, Mhmad Ali³, Marwa Fuad, Othman Ali³, Naif Mohammed Al-Haidary","doi":"10.1101/2024.08.12.24311851","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311851","url":null,"abstract":"Background: Intestinal parasite infection is a significant public health problem worldwide. This study aimed to determine the prevalence of intestinal parasites among primary school children, identify the most common types of parasites, and identify the risk factors contributing to infection in Aden, Yemen. Methodology/Principal Findings: An analytical cross-sectional study was conducted on 201 school children in Aden, Yemen. Stool specimens were collected and tested using direct methods (saline and iodine preparations) and sedimentation concentration techniques. Data analysis was performed using SPSS (Version 21) with p <= 0.05 considered statistically significant. The overall prevalence of intestinal parasites was 47.3%; 35.8% had a single parasite and 11.5% had multiple parasites. Higher rates were observed among female schoolchildren (51.2%), children whose mothers had primary education (51.3%), secondary education (50%), housewives (48.5%), and children aged >9 years (50%). The most predominant parasite was Entamoeba histolytica/dispar (36.3%). There was no significant association between the identified risk factors and intestinal parasitic infections. Conclusions/Significance: The prevalence rate of intestinal parasites is high in Aden, Yemen, with Entamoeba histolytica/dispar being the most dominant parasite. The highest rates were found among female schoolchildren, those whose mothers were housewives with primary or secondary education, and children aged >9 years.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"23 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted inference to identify drug repositioning candidates in the Danish health registries","authors":"A. W. Jung, I. Louloudis, S. Brunak, L. Mortensen","doi":"10.1101/2024.08.12.24311869","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311869","url":null,"abstract":"Electronic health records can be used to track diagnoses and drug prescriptions in large heterogeneous populations over time. Coupled with recent advances in causal inference from observational data, these records offer new opportunities to emulate clinical trials and identify potential targets for drug repositioning. Here, we run a hypothesis generating cohort study of Danes aged 50 to 80 years from 2001 to 2015 (n = 2,512,380), covering a total of 23,371,354 years of observations. We examine prescription drugs at ATC level-4 and their effect on 9 major disease outcomes. Using Bayesian time-varying Cox regression and longitudinal minimum loss estimation, our analysis successfully reproduces known drug-disease associations from clinical trials, such as the reduction in the 3-year absolute risk of death associated with Statins (ATC:C10AA) -0.8% (95% CI =[-1.2%, -0.5%]) and -0.8% (95% CI =[-1.3%, -0.2%]) for females and males, respectively. Additionally, we discovered novel associations that suggest potential repositioning opportunities. For instance, Statins were associated with a reduction in the 3-year absolute risk of dementia by -0.3% (95% CI =[-0.5%, -0.1%]) for females and -0.2% (95% CI =[-0.4%, 0.1%]) for males. Furthermore, Biguanides (ATC:P01BB) stands out as a particularly interesting candidate with absolute risk reductions across various outcomes. In total, we identified 76 potential drug-disease pairs for further investigation. However, it should be stressed that the emulation of clinical trials here is solely of hypothesis generating nature and identified effects need to be corroborated with additional evidence, preferably from RTCs, as the risk of confounding by indication in this study is substantial. In summary, this study provides a large-scale screen of prescribed drugs and their effect on major debilitating disease in the Danish health registries. This provides an additional source of information that can be used in the search for possible repositioning candidates.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"39 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Its because they are my kids and I love them\": The impact of family and community substance use on children and families","authors":"Meghan Ford, Ryan Truong, Bruce Knox, Susan A. Bartels, Colleen Davidson, Michele Cole, Logan Jackson, Eva Purkey, Imaan Bayoumi","doi":"10.1101/2024.08.11.24311834","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311834","url":null,"abstract":"Background: Substance use disorders (SUD) significantly impact the physical, social, and mental health of individuals, their families, and the wider community. Parental substance use can lead to long-term social and health problems for children. Examining resilience and its determinants among families directly affected by SUD (e.g., having a parent who misuses substances) or indirectly exposed to substance use (e.g., living in a community impacted by drug use) may uncover valuable insights to support families addressing SUD. The existing literature does not adequately address substance use within the context of families with young children and community resilience. The current study aims to enhance our understanding of the daily impact of family member substance use (direct substance use) or exposure to substance use within the community (indirect substance use) on children and families through qualitative interviews. Methods: The present study was a qualitative secondary analysis. Families were recruited within the Kingston, Frontenac, Lennox, and Addington area during 2022 and 2023 with a focus on maximum variation. Families were eligible to participate if they: 1) included at least one adult caring for a child under 18; 2) had a history of adversity; 3) were interested in participating; and 4) could consent to all parts of the study. Arts-based qualitative methods and community based participatory methods were employed. Participating families created a visual timeline, participated in a focus group discussion, and an individual interview. The qualitative transcripts were then analyzed following reflexive thematic analysis. Findings: Six families (12 adults, 4 children) were included in the secondary analysis. The analysis generated four themes: (1) How children affect resilience in families affected by SUD; (2) Service needs of parents with SUD to enhance family resilience; (3) The role of social support in family resilience; and (4) How perceptions of safety and trust challenge community resilience. The main limitation of this study was a small sample size. Conclusions: The study highlights the significant impact of family and community on the resilience of individuals affected by SUD. It emphasizes the importance of developing addictions services and social environments that are supportive of families with young children. These spaces should be designed to be substance-free, inclusive, and welcoming to children. Additionally, there is a need to improve service navigation and address the barriers to care commonly experienced by individuals affected by SUD.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"40 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of food-based versus supplement-based very low-energy diets on gut microbiome composition and health outcomes in women with high body mass index (The MicroFit Study): a randomised controlled trial","authors":"Mohammadreza Mohebbi, Mojtaba Lotfaliany, Martin O’Hely, Jessica Batti, M. Kotowicz, Lucy Saunders, Richard Page, Sally Beatti, Wolfgang Marx, F. Jacka, Postdoctoral Mojtaba Lotfaliany, Research, Postdoctoral Martin O’Hely, Research Fellow c. Mark, Professor d. Michael Kotowicz, Berk, Research Sally Beattie, Affiliate, Dr Amelia J McGuinness","doi":"10.1101/2024.08.11.24311823","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311823","url":null,"abstract":"Objective: To compare the effects of consuming food-based versus supplement-based very low-energy diet (VLED) programs on gut microbiome composition in women with a high body mass index (BMI). Design: An investigator-initiated, single-blind, two-arm, parallel-group randomised controlled-feeding trial with computer-generated 1:1 randomisation. From May 2021 to February 2022, women aged 30-65 years with BMI 30-45 kg/m2 were recruited from southwest Victoria, Australia, and randomised to a three-week food-based or supplement-based VLED program. The primary outcome was between-group differential change in faecal microbiome alpha diversity (Shannon index) from baseline to week three, assessed using shotgun metagenomics. Outcome assessors, study investigators, and analysing statisticians were blinded to group allocation until analysis completion. Allocation concealment was managed by an independent researcher using a computer software system. Modified intention-to-treat (mITT) analyses using linear mixed-effects regression models estimated mean between-group differential changes, reported as beta-coefficient point estimates ({beta}) and 95% confidence intervals (95%CI), adjusted for multiple comparisons. Results: Forty-seven participants were randomised (food-based: n=23, supplement-based: n=24). Of the 45 participants analysed, there was a between-group differential change in the Shannon index (mITT {beta}: 0.37, 95%CI: 0.15 to 0.60) from baseline to week three, with a greater increase in the food-based group (mean change: 0.26, 95%CI: 0.09 to 0.44; n=23) versus supplement-based group (mean change: -0.10, 95%CI: -0.25 to 0.05; n=22). There were 27 non-serious adverse events (food-based: 8, supplement-based: 19), all non-serious. Conclusion: A food-based VLED, with more whole food components and fewer highly processed industrial ingredients, increases gut microbiome diversity more than a supplement-based VLED.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}