Multivariable Association Discovery in Population-scale Meta-omics Studies

Mallick, Himel; Rahnavard, Ali; McIver, Lauren J.; Ma, Siyuan; Zhang, Yancong; Nguyen, Long H.; Tickle, Timothy L.; Weingart, George; Ren, Boyu; Schwager, Emma; Chatterjee, Suvo; Thompson, Kelsey N.; Wilkinson, Jeremy E.; Subramanian, Ayshwarya; Lu, Yiren; Waldron, Levi; Paulson, Joseph N.; Franzosa, Eric A.; Bravo, Héctor Corrada; Huttenhower, Curtis

doi:10.1101/2021.01.20.427420

Cited by 299 publications

(222 citation statements)

References 66 publications

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“…To test associations involving bacteria taxa showing significant difference in abundance by HIV-1 status and clinical and immunological markers, correlation analysis was performed using R package Hmisc v4.5. Multivariate analysis of phenotypes with significant correlation was performed to ascertain association using Microbiome Multivariable Associations with Linear Models, MaAsLin2 (Mallick et al, 2021).…”

Section: Statistical Analysesmentioning

confidence: 99%

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana

Parbie

Mizutani

Ishizaka

et al. 2021

Front. Cell. Infect. Microbiol.

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HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses of gut/fecal microbiome in individual regions are important for our understanding of pathogenesis in HIV-1 infections. However, data on gut/fecal microbiome has not yet been accumulated in West Africa. In the present study, we examined fecal microbiome compositions in HIV-1 infected adults in Ghana, where approximately two-thirds of infected adults are females. In a cross-sectional case-control study, age- and gender-matched HIV-1 infected adults (HIV+; n = 55) and seronegative controls (HIV-; n = 55) were enrolled. Alpha diversity of fecal microbiome in HIV+ was significantly reduced compared to HIV- and associated with CD4 counts. HIV+ showed reduction in varieties of bacteria including Faecalibacterium, the most abundant in seronegative controls, but enrichment of Proteobacteria. Ghanaian HIV+ exhibited enrichment of Dorea and Blautia; bacteria groups whose depletion has been reported in HIV-1 infected individuals in several other cohorts. Furthermore, HIV+ in our cohort exhibited a depletion of Prevotella, a genus whose enrichment has recently been shown in men having sex with men (MSM) regardless of HIV-1 status. The present study revealed the characteristics of dysbiotic fecal microbiome in HIV-1 infected adults in Ghana, a representative of West African populations.

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Section: Statistical Analysesmentioning

confidence: 99%

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana

Parbie

Mizutani

Ishizaka

et al. 2021

Front. Cell. Infect. Microbiol.

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show abstract

“…distance-based redundancy analysis were performed using the R package vegan [28]. Per-feature tests for the association between specific microbial species and clinical biomarkers were done using the R package MaAsLin2 [29]. Further information regarding data processing and sample size calculation was previously reported [25].…”

Section: Discussionmentioning

confidence: 99%

Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions

Rinott

Youngster

Meir

et al. 2021

European Journal of Internal Medicine

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Background:We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation. Methods: In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0-6 m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100 g) during the expected weight regain phase (8-14 m). Results: Of the 90 participants (age=52 yr; 0-6 m weight loss=-8.3 kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6 m, whereas 6 m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8-14 m aFMT administration phase, aFMT maintained decreased levels of leptin (ΔaFMT=-3.54 ng/mL vs. Δplacebo=-0.82 ng/mL;P = 0.04), C-reactive-protein (ΔaFMT=-1.45 mg/L vs. Δplacebo=-0.66 mg/L; P = 0.009), Interleukin-6 (ΔaFMT=-0.03pg/mL vs. Δplacebo=1.11pg/mL;P = 0.03) and total cholesterol (ΔaFMT=2.2 mg/dl vs. Δplacebo=13.1 mg/dl;P = 0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P = 0.03;Jensen-Shannon distance), as compared to placebo. Conclusions: aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.

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“…Based on the ASV abundances from 16S rRNA sequencing, KEGG orthologs, EC numbers, and MetaCyc pathways were inferred. Within the MaAsLin2 framework, a linear regression with default settings was applied to test whether specific metabolic pathways were enriched by VD or MD [35].…”

Section: Picrustmentioning

confidence: 99%

Changes in Gut Microbiota after a Four-Week Intervention with Vegan vs. Meat-Rich Diets in Healthy Participants: A Randomized Controlled Trial

et al. 2021

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An essential role of the gut microbiota in health and disease is strongly suggested by recent research. The composition of the gut microbiota is modified by multiple internal and external factors, such as diet. A vegan diet is known to show beneficial health effects, yet the role of the gut microbiota is unclear. Within a 4-week, monocentric, randomized, controlled trial with a parallel group design (vegan (VD) vs. meat-rich (MD)) with 53 healthy, omnivore, normal-weight participants (62% female, mean 31 years of age), fecal samples were collected at the beginning and at the end of the trial and were analyzed using 16S rRNA gene amplicon sequencing (Clinical Trial register: DRKS00011963). Alpha diversity as well as beta diversity did not differ significantly between MD and VD. Plotting of baseline and end samples emphasized a highly intra-individual microbial composition. Overall, the gut microbiota was not remarkably altered between VD and MD after the trial. Coprococcus was found to be increased in VD while being decreased in MD. Roseburia and Faecalibacterium were increased in MD while being decreased in VD. Importantly, changes in genera Coprococcus, Roseburia and Faecalibacterium should be subjected to intense investigation as markers for physical and mental health.

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Multivariable Association Discovery in Population-scale Meta-omics Studies

Cited by 299 publications

References 66 publications

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana

Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions

Changes in Gut Microbiota after a Four-Week Intervention with Vegan vs. Meat-Rich Diets in Healthy Participants: A Randomized Controlled Trial

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