Abstract MP11: Effects of Metformin and Behavioral Weight Loss on the Gut Microbiome

Background: Evidence suggests metformin and behavioral weight loss alter the gut microbiome, with weight loss associated with higher diversity and metformin with higher Escherichia Coli . Yet randomized trials on these interventions are limited. Objective: To examine the hypothesis that metformin increases E. Coli and and behavioral weight loss increases diversity. Methods: We conducted a parallel-arm, randomized trial in which we enrolled overweight or obese adult cancer survivors who had been previously treated for solid tumors, but without active disease or ongoing cancer treatment. We randomized participants (n=121) to: 1) coach-directed behavioral weight loss (with advice on the DASH diet), 2) metformin, or 3) self-directed weight loss (control). We collected stool at baseline, 6 mo. and 12 mo. and extracted microbial DNA from stool to measure the microbiome with 16S rRNA sequencing of the V4 region. We used ‘Aldex2’ in R to examine the effect of treatments on the change in relative abundance of microbial taxa amplicon sequence variants from baseline to 6 mo. and 12 mo. Results: Groups did not differ by sex (79% female), race (45% black) or age (mean 60 yrs). Mean weight loss was 3.9%, 2.7%, and 0.9% in coach-directed, metformin, and self-directed arms at 6-mo., respectively (both P s<0.05 compared to self-directed.) There were no differences within or between arms in measures of alpha or beta diversity ( P s>0.05). Only the metformin arm altered the relative abundance of microbiota ( Figure ). From baseline, metformin increased relative abundance of E. Coli and decreased relative abundance of butyrate-producing Ruminococcus Intestinalis and Intestinibacter Bartletti at 6 mo. and 12 mo. Metformin also decreased Roseburia Faecis at 6 mo. and increased Ruminococcus Torques at 12 mo. ( Figure ). Conclusion: Metformin increased E. Coli and decreased several butyrate-producing genera, but was not associated with microbiome diversity. Moderate behavioral weight loss (~3.9%) did not alter microbiome diversity or composition.

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The Infant Gut Resistome is Associated with E. coli and Early-life Exposures

10.21203/rs.3.rs-52285/v1 ◽

2020 ◽

Author(s):

Rebecca M. Lebeaux ◽

Modupe O. Coker ◽

Erika F. Dade ◽

Thomas J. Palys ◽

Hilary G. Morrison ◽

...

Keyword(s):

Antibiotic Resistance ◽

Relative Risk ◽

Relative Abundance ◽

Gut Microbiome ◽

Early Life ◽

The United States ◽

Delivery Mode ◽

Metagenomic Sequencing ◽

E Coli ◽

Early Life Exposures

Abstract Background: Antibiotic resistance is an increasing threat to human health. The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood and clarifying these factors would inform strategies to decrease antibiotic resistance. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling was used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs.Results: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33-36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54-5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux (i.e., by pumping antibiotics out of the cell). The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically E. coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97 – 1.29)] as well as a having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12 – 1.84)] at 1 year compared to infants born vaginally. Additionally, 6 specific ARGs were at a greater relative abundance in infants delivered by cesarean section compared to vaginally delivered infants across both time points. Conclusions: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the possibility of antibiotic resistant life threatening infections.

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0135 Self-Reported Sleep and Gut Microbiome Composition and Diversity: Associations in Well-Functioning Older Adults

SLEEP ◽

10.1093/sleep/zsaa056.133 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A53-A53

Author(s):

C Holingue ◽

N T Mueller ◽

T Tanaka ◽

M K Differding ◽

C W Chia ◽

...

Keyword(s):

Older Adults ◽

Sleep Duration ◽

Relative Abundance ◽

Gut Microbiome ◽

Rating Scale ◽

Self Report ◽

Microbiome Composition ◽

Microbiome Diversity ◽

Falling Asleep ◽

Insomnia Symptoms

Abstract Introduction The gut microbiome is believed to play an important role in health and disease, yet little is known about the link between sleep and the gut microbiome in humans. We investigated the association of self-reported sleep with gut microbiome composition and diversity in a cohort of well-functioning older adults. Methods We studied 791 participants (mean age = 71.5±12.0 years, 55% women) in the Baltimore Longitudinal Study of Aging with self-report sleep measures and whole-genome DNA sequencing of stool samples. Predictors (modeled as continuous variables) included insomnia symptoms from the Women’s Health Initiative Insomnia Rating Scale (WHIIRS), sleep duration (<5, 5–6, 6–7, >7 hours), and frequency of excessive daytime sleepiness (EDS). We tested their association with gut microbiome diversity (Shannon index) and relative abundance of individual taxa using Kendall Tau Correlation. Next, we assessed whether these sleep variables were associated with overall microbiome structure (Bray-Curtis), adjusting for age, sex, race, education, BMI, depressive symptoms, and number of comorbidities. Results Sleep duration was associated with overall microbiome composition (p<0.01), with longer sleep duration associated with lower biodiversity of microbes in the gut (p<0.05). In phylum-level analyses, higher WHIIRS total (i.e., more severe insomnia) was associated with lower relative abundance of Actinobacteria, while more frequent EDS was associated with lower relative abundance of Fusobacteria. More frequent trouble falling asleep, staying asleep, early waking, poorer sleep quality and higher WHIIRS total were associated with lower abundance of Synergistetes (all p<0.05). Conclusion In well-functioning older adults, self-reported sleep duration, symptoms of insomnia, and EDS were associated with microbiome diversity and composition. The phylum Synergistetes, which has been associated with protective humoral immune response in prior literature, may be an important correlate of insomnia symptoms in older adults. Future investigations are needed to examine the gut microbiome as a driver or mediator of sleep-health associations. Support This study was supported in part by National Institute on Aging (NIA) grant R01AG050507, the NIA Intramural Research Program (IRP), and Research and Development Contract HHSN-260-2004-00012C.

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Pharmacologically induced weight loss is associated with distinct gut microbiome changes in obese rats

10.1101/2021.05.06.442639 ◽

2021 ◽

Author(s):

Silvia Raineri ◽

Julia A Sherriff ◽

Kevin S.J Thompson ◽

Huw Jones ◽

Paul T Pfluger ◽

...

Keyword(s):

Weight Loss ◽

Food Intake ◽

Detailed Analysis ◽

Relative Abundance ◽

Gut Microbiome ◽

Bacterial Species ◽

Shotgun Metagenomics ◽

Fecal Microbiome ◽

Obese Rats ◽

The Impact

Background: Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the fecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct gut microbiome species and their respective gene programs in obese individuals. Results: Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination. We found that sibutramine treatment induced consistent weight loss through reducing food intake. Decreased weight loss in sibutramine-treated rats was associated with changes to the gut microbiome that included increased beta-diversity, increased Bacteroides/Firmicutes ratio and increased relative abundance of multiple Bacteroides species. In addition, the relative abundance of multiple genes was found to be differentially abundant, including significant reductions in components of flagellum and genes involved in flagellum assembly. Conclusions: This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibutramine-induced weight loss, we have identified multiple weight-loss associated microbial taxa and pathways. These include a reduction in components of flagellum and the flagellum assembly pathway that points to a potential role of sibutramine-induced weight-loss on regulating bacterially driven anti-inflammatory responses.

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Abstract MP16: A Behavioral Weight-loss Intervention, But Not Metformin, Decreases A Marker Of Gut Barrier Permeability In Adult Cancer Survivors With Overweight Or Obesity

Circulation ◽

10.1161/circ.143.suppl_1.mp16 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Curtis Tilves ◽

Hsin-Chieh Yeh ◽

Nisa Maruthur ◽

Stephen Juraschek ◽

Edgar R Miller ◽

...

Keyword(s):

Weight Loss ◽

Cancer Survivors ◽

Weight Loss Intervention ◽

Fiber Intake ◽

Behavioral Weight Loss ◽

Gut Permeability ◽

Gut Barrier ◽

Adult Cancer Survivors ◽

Behavioral Weight Loss Intervention ◽

Overweight Or Obesity

Background: Serum lipopolysaccharide-binding protein (LBP), a surrogate biomarker for gut barrier permeability, is higher in adults with obesity and type 2 diabetes and may trigger inflammation. It is unknown whether a behavioral weight loss intervention or metformin — current first-line treatments for obesity or diabetes — can reduce gut permeability. Objective: To determine the effects of behavioral weight loss intervention or metformin, compared to self-directed weight loss, on serum LBP. Methods: SPIRIT was a parallel-arm, randomized trial of adult cancer survivors with overweight or obesity. Participants were randomized to a self-directed weight loss (control), metformin, or coach-directed (healthy diet/physical activity) weight loss arm. Of 121 randomized participants, a random subset (n=88) had LBP measured at baseline, 6-months, and 12-months post intervention. The effects of interventions on LBP over time were assessed using generalized estimating equations (GEE). Models were further adjusted for absolute change in fiber intake to investigate potential mediation. Results: Arms were balanced by sex (83% female), race (48% black), and age (mean 60 years). There were no between-group differences in LBP at baseline (median 42.3 μg/dL). Over the 12-month period, only the coach-directed and metformin arms showed weight loss (both mean -3% from baseline). Similar increases in LBP were seen in the self-directed and metformin arms, while a decrease in LBP was seen in the coach-directed arm ( figure ). In GEE models, the difference in slopes between the coach vs. self-directed arms was statistically significant (β=-1.67, p=0.037), but not between the metformin and self-directed arms (β=0.003, p=0.997). The effect of coach-directed weight loss on LBP was similar by sex and race and was not mediated by changes in fiber intake. Conclusion: The manner of weight loss can differentially impact gut permeability and thus subsequent exposure to proinflammatory microbial products.

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Dietary and weight loss effects on human gut microbiome diversity and metabolism

Diabetologie und Stoffwechsel ◽

10.1055/s-0036-1580913 ◽

2016 ◽

Vol 11 (S 01) ◽

Author(s):

D Fangmann ◽

FA Heinsen ◽

DM Schulte ◽

MC Rühlemann ◽

K Türk ◽

...

Keyword(s):

Weight Loss ◽

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome ◽

Microbiome Diversity

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180. Alterations to the Gut Microbiomes and Acquisition of Bacteria Resistance Elements among US International Travelers

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.180 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S110-S110

Author(s):

Sushmita Sridhar ◽

Colin Worby ◽

Ryan Bronson ◽

Sarah Turbett ◽

Jason Harris ◽

...

Keyword(s):

Antibiotic Resistance ◽

South America ◽

South Asia ◽

Relative Abundance ◽

Resistance Genes ◽

Gut Microbiome ◽

International Travel ◽

South East Asia ◽

E Coli ◽

Geographic Regions

Abstract Background This study investigated the impact of international travel on the acquisition and carriage of antimicrobial resistance (AMR). We prospectively assessed U.S. international travelers for the acquisition of resistant Enterobacterales species and evaluated changes in travelers’ gut microbiomes. Methods Metagenomic sequencing was performed on DNA extracted from pre- and post-travel stool samples of 273 U.S. international travelers. We used Kraken2 to assess microbial gut composition and analyzed antibiotic resistance gene (ARG) content using the Resistance Gene Identifier (RGI) and ResFinder, and read mapping to ARG databases. We assessed the change in gut profile and resistome associated with (i) all international travel; (ii) travel to specific geographic regions; and (iii) traveler’s diarrhea. Results International travel resulted in a perturbation of the gut microbiome, which was greater in travelers receiving treatment for diarrhea during travel (p = 4E-5). There was an overall loss in microbial diversity following travel, regardless of health outcome (p = 0.011); this was most consistently observed in travelers to South East Asia (SEA) (loss of gut diversity in 81% of SEA travelers). 78% of all travelers had a higher relative abundance of E. coli after travel, including 85% of travelers who acquired AMR bacteria during travel. Travel to South Asia was also associated with a significantly greater increase of E. coli relative to other destinations (p = 0.04). Additionally, the relative abundance of Pasteurellales was higher in the pre-travel samples of those who subsequently acquired AMR bacteria (FDR = 0.08). Furthermore, there was a significant increase in ARG content among the post-travel samples, with regional differences in the magnitude of acquisition (Figure 1). 72% of all travelers had a greater resistance burden post-travel. SEA was associated with the greatest increase in resistome diversity, while South America was associated with the greatest increase in overall ARG content. Resistance genes present in the gut microbiome. Genes mapping to the Comprehensive Antibiotic Resistance Database were measured pre- (x-axis) and post-travel (y-axis) to assess the acquisition of resistance genes in association with travel, distinguished by geographic region. Colors indicate geographic regions visited by travelers: South America (red), South East Asia (blue), South Asia (green), Eastern Africa (purple), Southern Africa (orange), Other (grey). Conclusion International travel is associated with a perturbation in the gut microbial community, with the acquisition of AMR bacteria and genes, and an increase in the relative abundance of E. coli. These perturbations following travel may be important factors in the global spread of AMR. Disclosures All Authors: No reported disclosures

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Beneficial Effects of a Dietary Weight Loss Intervention on Human Gut Microbiome Diversity and Metabolism Are Not Sustained during Weight Maintenance

Obesity Facts ◽

10.1159/000449506 ◽

2016 ◽

Vol 9 (6) ◽

pp. 379-391 ◽

Cited By ~ 20

Author(s):

Femke-Anouska Heinsen ◽

Daniela Fangmann ◽

Nike Müller ◽

Dominik M. Schulte ◽

Malte C. Rühlemann ◽

...

Keyword(s):

Weight Loss ◽

Gut Microbiome ◽

Weight Maintenance ◽

Weight Loss Intervention ◽

Human Gut ◽

Human Gut Microbiome ◽

Beneficial Effects ◽

Microbiome Diversity ◽

Dietary Weight Loss

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Dietary and weight loss effects on human gut microbiome diversity and metabolism

Endocrine Abstracts ◽

10.1530/endoabs.41.gp138 ◽

2016 ◽

Author(s):

Daniela Fangmann ◽

Femke-Anouska Heinsen ◽

Dominik M Schulte ◽

Malte-Christoph Ruhlemann ◽

Kathrin Turk ◽

...

Keyword(s):

Weight Loss ◽

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome ◽

Microbiome Diversity

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Pharmacologically Induced Weight Loss Is Associated With Distinct Gut Microbiome Changes In Obese Rats

10.21203/rs.3.rs-544257/v2 ◽

2021 ◽

Author(s):

Silvia Raineri ◽

Julia A Sherriff ◽

Kevin S.J. Thompson ◽

Huw Jones ◽

Paul T Pfluger ◽

...

Keyword(s):

Weight Loss ◽

Food Intake ◽

Detailed Analysis ◽

Relative Abundance ◽

Gut Microbiome ◽

Bacterial Species ◽

Shotgun Metagenomics ◽

Fecal Microbiome ◽

Obese Rats ◽

The Impact

Abstract Background: Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the fecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct gut microbiome species and their respective gene programs in obese individuals. Results: Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four investigatory or approved anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination. We found that sibutramine treatment induced consistent weight loss through reducing food intake. Weight loss in sibutramine-treated rats was associated with changes to the gut microbiome that included increased beta-diversity, increased Bacteroides/Firmicutes ratio and increased relative abundance of multiple Bacteroides species. In addition, the relative abundance of multiple genes was found to be differentially abundant, including significant reductions in components of flagellum and genes involved in flagellum assembly. Conclusions: This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibutramine-induced weight loss, we have identified multiple weight-loss associated microbial taxa and pathways. These include a reduction in components of flagellum and the flagellum assembly pathway that points to a potential role of sibutramine-induced weight-loss on regulating bacterially driven anti-inflammatory responses.

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Effects of a Behavioral Weight Loss Intervention and Metformin Treatment on Serum Urate: Results from a Randomized Clinical Trial

Nutrients ◽

10.3390/nu13082673 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2673

Author(s):

Jiun-Ruey Hu ◽

Hsin-Chieh Yeh ◽

Noel T. Mueller ◽

Lawrence J. Appel ◽

Edgar R. Miller ◽

...

Keyword(s):

Weight Loss ◽

Cancer Survivors ◽

Randomized Trial ◽

Controlled Trial ◽

Serum Urate ◽

The Self ◽

Metformin Treatment ◽

Behavioral Weight Loss ◽

Directed Group ◽

Adult Cancer Survivors

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): −1.5, −0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: −1.1, −0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: −0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.

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