scholarly journals Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

2021 ◽  
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa Maruthar ◽  
Stephen P Juraschek ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gut Microbiota ◽  
Randomized Trial ◽  
Short Chain Fatty Acids ◽  
Metagenomic Sequencing ◽  
Microbiota Composition ◽  
Behavioral Weight Loss ◽  
Microbiome Composition ◽  
Weight Loss Group ◽  
And Function

<b>Objective:</b> To determine the longer-term effects of metformin and behavioral weight loss on gut microbiota and SCFAs. <p><b>Methods: </b>We conducted a parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n=121) to: 1) metformin (up to 2000mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n=114), 6 months (n=109) and 12 months (n=105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. </p> <p><b>Results: </b>Of the 121 participants, 79% were female, 46% were black, and the mean age was 60y. Only metformin intervention significantly altered microbiota composition. Compared to control, metformin increased <i>E. Coli</i> and <i>Ruminococcus torques</i> and decreased <i>Intestinibacter Bartletti</i> at both 6 and 12 months, and decreased the genus <i>Roseburia (genus)</i>, including <i>R. faecis</i> and <i>R. intestinalis,</i> at 12 months. Effects were similar when comparing metformin to the behavioral weight loss group. Metformin also altered 62 metagenomic functional pathways and increased butyrate, acetate, and valerate at 6 months. Behavioral weight loss vs. control did not significantly alter microbiota composition, but did increase acetate at 6 months. Increases in acetate were associated with decreases in fasting insulin.</p> <p><b>Conclusions:</b> Metformin, but not behavioral weight loss, impacted gut microbiota composition and function at 6 months and 12 months. Both metformin and behavioral weight loss altered 6-month SCFAs, including increasing acetate which correlated with improved insulin sensitivity.</p>

scholarly journals Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

2021 ◽  
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa Maruthar ◽  
Stephen P Juraschek ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gut Microbiota ◽  
Randomized Trial ◽  
Short Chain Fatty Acids ◽  
Metagenomic Sequencing ◽  
Microbiota Composition ◽  
Behavioral Weight Loss ◽  
Microbiome Composition ◽  
Weight Loss Group ◽  
And Function

<b>Objective:</b> To determine the longer-term effects of metformin and behavioral weight loss on gut microbiota and SCFAs. <p><b>Methods: </b>We conducted a parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n=121) to: 1) metformin (up to 2000mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n=114), 6 months (n=109) and 12 months (n=105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. </p> <p><b>Results: </b>Of the 121 participants, 79% were female, 46% were black, and the mean age was 60y. Only metformin intervention significantly altered microbiota composition. Compared to control, metformin increased <i>E. Coli</i> and <i>Ruminococcus torques</i> and decreased <i>Intestinibacter Bartletti</i> at both 6 and 12 months, and decreased the genus <i>Roseburia (genus)</i>, including <i>R. faecis</i> and <i>R. intestinalis,</i> at 12 months. Effects were similar when comparing metformin to the behavioral weight loss group. Metformin also altered 62 metagenomic functional pathways and increased butyrate, acetate, and valerate at 6 months. Behavioral weight loss vs. control did not significantly alter microbiota composition, but did increase acetate at 6 months. Increases in acetate were associated with decreases in fasting insulin.</p> <p><b>Conclusions:</b> Metformin, but not behavioral weight loss, impacted gut microbiota composition and function at 6 months and 12 months. Both metformin and behavioral weight loss altered 6-month SCFAs, including increasing acetate which correlated with improved insulin sensitivity.</p>

scholarly journals Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

Diabetes Care ◽  
2021 ◽  
pp. dc202257
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa M. Maruthur ◽  
Stephen P. Juraschek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Randomized Trial ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Microbiome Composition ◽  
And Function ◽  
Chain Fatty Acids

scholarly journals Dietary Inulin Supplementation Modulates Short-Chain Fatty Acid Levels and Cecum Microbiota Composition and Function in Chickens Infected With Salmonella

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiao Song ◽  
Qinghe Li ◽  
Nadia Everaert ◽  
Ranran Liu ◽  
Maiqing Zheng ◽  
...  
Keyword(s):  
Basal Diet ◽  
Short Chain Fatty Acids ◽  
Nucleotide Metabolism ◽  
Short Chain ◽  
Control Group ◽  
Sequencing Analysis ◽  
Metagenomic Sequencing ◽  
Microbiome Composition ◽  
And Function ◽  
Functional Profiles

The current study investigated the effects of inulin on the gut microbiota, microbiome functions, and short-chain fatty acids (SCFAs) levels in specific pathogen-free (SPF) chickens infected with Salmonella enteritidis (SE). SPF Arbor Acres chickens (n = 240, 1-day-old) were divided into four groups: a control group (CON) fed a basal diet without inulin supplementation or SE infection, and three groups fed a basal diet supplemented with inulin 0, 0.5, and 1% (SE, 0.5%InSE, 1%InSE, respectively) up to 28-days-old, followed by SE challenge at 28 days of age. Cecal SCFA contents and microbiome composition and function were analyzed at 1-day post-infection. The results showed that SE infection significantly decreased cecal butyrate concentrations compared with the CON group (p &lt; 0.05), while inulin supplementation reversed these changes compared with the SE group (p &lt; 0.05). Inulin supplementation at 1% significantly increased the abundances of Lactobacillus and Streptococcus, and significantly decreased the abundances of Subdoligranulum and Sellimonas compared with the SE group (p &lt; 0.05). The functional profiles of microbial communities based on metagenomic sequencing analysis showed that SE infection significantly increased the abundances of pathways related to carbohydrate metabolism, amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and glycan biosynthesis and metabolism (p &lt; 0.05), and significantly decreased the abundances of pathways related to nucleotide metabolism, translation, and replication and repair compared with the CON group (p &lt; 0.05), and these effects were reversed by inulin supplementation (0.5 and 1%) (p &lt; 0.05). In conclusion, inulin modulated the dysbiosis induced by SE infection via affecting SCFA metabolism and microbial functional profiles.

scholarly journals Changes in the Gut Microbiota During a Weight Loss Intervention of Daily Caloric Restriction Versus Intermittent Fasting: The DRIFT2 Randomized Clinical Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1588-1588
Author(s):  
Maggie Stanislawski ◽  
Purevsuren Jambal ◽  
Diana Ir ◽  
Danielle Ostendorf ◽  
Kristen Bing ◽  
...  
Keyword(s):  
Weight Loss ◽  
Waist Circumference ◽  
Gut Microbiota ◽  
Caloric Restriction ◽  
Intermittent Fasting ◽  
Microbiota Composition ◽  
Weight Loss Intervention ◽  
Behavioral Weight Loss ◽  
Behavioral Weight Loss Intervention ◽  
Over Time

Abstract Objectives Intermittent fasting (IMF) is an alternative to the standard weight loss approach of daily caloric restriction (DCR). Although altered gut microbiota has been linked to obesity and may influence weight loss, it is unknown how the gut microbiota is impacted by these weight loss strategies or its association with responsiveness. In this study, we examine the gut microbial diversity and composition during an intervention of DCR versus IMF. Methods Fecal microbiota communities were profiled by 16S rRNA gene sequencing in 59 individuals with overweight and obesity (mean BMI: 33.1 (SD: 4.4) kg/m2, age: 40.7 (SD: 9.8) years; 76.3% female) undergoing a comprehensive, group-based behavioral weight loss intervention of DCR (n = 25) versus IMF (n = 34) at baseline and 3-months into the intervention. Mixed effects linear regressions, permutational ANOVA, and ANCOM were used to examine differences in gut microbiota over time and by intervention group, and regression-based methods were used to examine the association between baseline gut microbiota and percentage change in weight and waist circumference. Results Overall, participants lost 5.9 (SD: 3.7) kilograms at 3 months. Weight loss within groups is not reported, as the trial is ongoing. Alpha diversity increased in both intervention groups (P &lt; 0.034), with no significant differences between groups (P &gt; 0.847). Microbiota composition (beta diversity) changed significantly (R2 = 7.1%; P = 0.001) over the course of the intervention, with no significant differences between groups (P &gt; 0.325). Numerous taxa showed changes over time with differences between groups (FDR &lt; 0.05). Baseline gut microbiota composition significantly predicted change in waist circumference (P = 0.009) but not in weight (P = 0.172). Conclusions Our results support that a behavioral weight loss intervention of reduced energy intake impacts gut microbiota with some differences between DCR and IMF, which may provide insight into the physiological effects of these weight loss approaches. The baseline gut microbiota was significantly associated with decrease in waist circumference. These results may inform ways to target the gut microbiota before initiating weight loss in order to improve responsiveness. Funding Sources NIH NIDDK R01; AHA Innovative Project Award.

scholarly journals The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre

2021 ◽  
Author(s):  
Dominic Salamone ◽  
Angela Albarosa Rivellese ◽  
Claudia Vetrani
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Dietary Fibre ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Microbiota Composition ◽  
The Relationship ◽  
Chain Fatty Acids

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.

A Crucial Role for Diet in the Relationship Between Gut Microbiota and Cardiometabolic Disease

2020 ◽  
Vol 71 (1) ◽  
pp. 149-161 ◽  
Author(s):  
Ilias Attaye ◽  
Sara-Joan Pinto-Sietsma ◽  
Hilde Herrema ◽  
Max Nieuwdorp
Keyword(s):  
Gut Microbiota ◽  
Global Scale ◽  
Cardiometabolic Disease ◽  
Microbiota Composition ◽  
Dietary Interventions ◽  
Fermentable Carbohydrates ◽  
Cost Efficient ◽  
And Function ◽  
Gut Microbiota Composition

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.

BestFIT Sequential Multiple Assignment Randomized Trial Results: A SMART Approach to Developing Individualized Weight Loss Treatment Sequences

2021 ◽  
Author(s):  
Nancy E Sherwood ◽  
A Lauren Crain ◽  
Elisabeth M Seburg ◽  
Meghan L Butryn ◽  
Evan M Forman ◽  
...  
Keyword(s):  
Weight Loss ◽  
Randomized Trial ◽  
Controlled Trial ◽  
Response Assessment ◽  
Optimal Time ◽  
Behavioral Weight Loss ◽  
Weight Loss Treatment ◽  
Adaptive Intervention ◽  
Weight Losses ◽  
Multiple Assignment

Abstract Background State-of-the-art behavioral weight loss treatment (SBT) can lead to clinically meaningful weight loss, but only 30–60% achieve this goal. Developing adaptive interventions that change based on individual progress could increase the number of people who benefit. Purpose Conduct a Sequential Multiple Assignment Randomized Trial (SMART) to determine the optimal time to identify SBT suboptimal responders and whether it is better to switch to portion-controlled meals (PCM) or acceptance-based treatment (ABT). Method The BestFIT trial enrolled 468 adults with obesity who started SBT and were randomized to treatment response assessment at Session 3 (Early TRA) or 7 (Late TRA). Suboptimal responders were re-randomized to PCM or ABT. Responders continued SBT. Primary outcomes were weight change at 6 and 18 months. Results PCM participants lost more weight at 6 months (−18.4 lbs, 95% CI −20.5, −16.2) than ABT participants (−15.7 lbs, 95% CI: −18.0, −13.4), but this difference was not statistically significant (−2.7 lbs, 95% CI: −5.8, 0.5, p = .09). PCM and ABT participant 18 month weight loss did not differ. Early and Late TRA participants had similar weight losses (p = .96), however, Early TRA PCM participants lost more weight than Late TRA PCM participants (p = .03). Conclusions Results suggest adaptive intervention sequences that warrant further research (e.g., identify suboptimal responders at Session 3, use PCMs as second-stage treatment). Utilizing the SMART methodology to develop an adaptive weight loss intervention that would outperform gold standard SBT in a randomized controlled trial is an important next step, but may require additional optimization work. Clinical Trial information ClinicalTrials.gov identifier; NCT02368002

scholarly journals Effects of Rich in Β-Glucans Edible Mushrooms on Aging Gut Microbiota Characteristics: An In Vitro Study

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2806 ◽  
Author(s):  
Evdokia K. Mitsou ◽  
Georgia Saxami ◽  
Emmanuela Stamoulou ◽  
Evangelia Kerezoudi ◽  
Eirini Terzi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Wheat Straw ◽  
In Vitro Study ◽  
Short Chain Fatty Acids ◽  
Edible Mushrooms ◽  
Elderly Subjects ◽  
Microbiota Composition ◽  
The Impact ◽  
Gut Microbiota Composition

Alterations of gut microbiota are evident during the aging process. Prebiotics may restore the gut microbial balance, with β-glucans emerging as prebiotic candidates. This study aimed to investigate the impact of edible mushrooms rich in β-glucans on the gut microbiota composition and metabolites by using in vitro static batch culture fermentations and fecal inocula from elderly donors (n = 8). Pleurotus ostreatus, P. eryngii, Hericium erinaceus and Cyclocybe cylindracea mushrooms derived from various substrates were examined. Gut microbiota composition (quantitative PCR (qPCR)) and short-chain fatty acids (SCFAs; gas chromatography (GC)) were determined during the 24-h fermentation. P. eryngii induced a strong lactogenic effect, while P. ostreatus and C. cylindracea induced a significant bifidogenic effect (p for all <0.05). Furthermore, P. eryngii produced on wheat straw and the prebiotic inulin had comparable Prebiotic Indexes, while P. eryngii produced on wheat straw/grape marc significantly increased the levels of tested butyrate producers. P. ostreatus, P. eryngii and C. cylindracea had similar trends in SCFA profile; H. erinaceus mushrooms were more diverse, especially in the production of propionate, butyrate and branched SCFAs. In conclusion, mushrooms rich in β-glucans may exert beneficial in vitro effects in gut microbiota and/or SCFAs production in elderly subjects.

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