Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.DesignEighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.ResultsIncreased MD adherence in the MedD group successfully reprogrammed subjects’ intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.ConclusionSwitching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.

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Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Scientific Reports ◽

10.1038/s41598-019-52103-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 9

Author(s):

Mette Simone Aae Madsen ◽

Jacob Bak Holm ◽

Albert Pallejà ◽

Pernille Wismann ◽

Katrine Fabricius ◽

...

Keyword(s):

Gut Microbiome ◽

Receptor Agonist ◽

Plasma Cholesterol ◽

Caloric Intake ◽

Abundant Species ◽

Shotgun Metagenomics ◽

Microbiome Composition ◽

Obesity And Diabetes ◽

Rdna Sequencing ◽

Glucagon Like Peptide

Abstract Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.

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Gut microbiome characteristics at the crossroads of metabolic health and lifestyle patterns in an adult population

Proceedings of The Nutrition Society ◽

10.1017/s0029665120004322 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Evdokia K. Mitsou ◽

M. Pilar Francino ◽

Maria Yannakoulia ◽

Smaragdi Antonopoulou ◽

Adamantini Kyriacou

Keyword(s):

Physical Activity ◽

Gut Microbiota ◽

Mediterranean Diet ◽

Dietary Patterns ◽

Gut Microbiome ◽

Dietary Pattern ◽

Adult Population ◽

Metabolic Health ◽

Activity Level ◽

Obesity Status

AbstractIntroductionCumulative findings have recently highlighted the role of gut microbiota as a novel environmental factor in the fight against obesity and related comorbidities. We aimed to investigate (1) the gut microbiome characteristics of a Greek adult population in terms of adiposity prevalence and (2) to further elucidate the potential effect of physical activity level and adherence to a-priori (Mediterranean Diet) and a-posteriori dietary patterns in gut microbiota profiling after accounting for sex, age and obesity status.Materials and MethodsAdult participants (n = 125) underwent clinical, anthropometric, dietary, physical activity and lifestyle evaluation. Obesity status [normal-weight (NW), overweight (OW), obesity (OB)] was defined based on body weight and height measurements, Body Mass Index calculation and the World Health Organization criteria. Levels of physical activity (low/medium/high) were estimated according to International Physical Activity Questionnaire (IPAQ) scoring. Dietary intake was evaluated through a food frequency questionnaire. Adherence to the Mediterranean diet was based on the MedDietScore and Principal Component Analysis (PCA) was applied for dietary patterns analysis. Gut microbial community characteristics (diversity, richness and proportions at phylum level) were calculated based on 16S rRNA gene sequencing.ResultsA total of 122 subjects (58 females; mean age 42.4 ± 13.1 years) completed the study. OB was characterized by lower proportions of Verrucomicrobia compared to NW state (p = 0.034 for univariate), unidentified bacteria (p = 0.014) and the Archaea Euryarchaeota (p = 0.003) compared to OW status, and the phylum Candidatus Saccharibacteria compared to NW (p = 0.027) and OW (p = 0.039) after sex and age adjustments. Regarding lifestyle parameters, our data proposed no significant effect of total physical activity levels on gut microbiome; notably, a ‘fruit and vegetables’ dietary pattern and adherence to Mediterranean diet were both characterized by lower microbial diversity and proportions of Actinobacteria but higher proportions of Cyanobacteria/Chloroplast and Lentisphaerae, respectively. Furthermore, a Western-type dietary pattern (high in full fat dairy products, potatoes, refined cereals, red meat, snacks and junkfood) was characterized by lower gut microbial richness (Chao1 index), whereas a healthy dietary pattern (high in low fat dairy and wholegrain cereals and low in snack and junk food) was characterized by higher proportion of Firmicutes.DiscussionOur data proposed variable connections of metabolic health and dietary patterns with features of gut microbiota; design of gut microbiome studies is advisable to account for host- and lifestyle-related potential confounders.

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Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: possible links with gut microbiome, insulin resistance and inflammation

European Journal of Nutrition ◽

10.1007/s00394-021-02538-8 ◽

2021 ◽

Author(s):

Silvia Tagliamonte ◽

Manolo Laiola ◽

Rosalia Ferracane ◽

Marilena Vitale ◽

Maria A. Gallo ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Mediterranean Diet ◽

Gut Microbiome ◽

Plasma Concentrations ◽

Endocannabinoid System ◽

Model Assessment ◽

Weight Changes ◽

Body Weight Changes ◽

Obese Subjects

Abstract Purpose To investigate whether a Mediterranean diet (MD) affected the plasma concentrations of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their specific ratios in subjects with lifestyle risk factors for metabolic diseases. To identify the relationship between circulating levels of these compounds and gut microbiome, insulin resistance and systemic inflammation. Methods A parallel 8-week randomised controlled trial was performed involving 82 overweight and obese subjects aged (mean ± SEM) 43 ± 1.4 years with a BMI of 31.1 ± 0.5 kg/m2, habitual Western diet (CT) and sedentary lifestyle. Subjects were randomised to consume an MD tailored to their habitual energy and macronutrient intake (n = 43) or to maintain their habitual diet (n = 39). Endocannabinoids and endocannabinoid-like molecules, metabolic and inflammatory markers and gut microbiome were monitored over the study period. Results The MD intervention lowered plasma arachidonoylethanolamide (AEA, p = 0.02), increased plasma oleoylethanolamide/palmitoylethanolamide (OEA/PEA, p = 0.009) and OEA/AEA (p = 0.006) and increased faecal Akkermansia muciniphila (p = 0.026) independent of body weight changes. OEA/PEA positively correlated with abundance of key microbial players in diet–gut–health interplay and MD adherence. Following an MD, individuals with low-plasma OEA/PEA at baseline decreased homeostatic model assessment of insulin resistance index (p = 0.01), while individuals with high-plasma OEA/PEA decreased serum high-sensitive C-reactive protein (p = 0.02). Conclusions We demonstrated that a switch from a CT to an isocaloric MD affects the endocannabinoid system and increases A. muciniphila abundance in the gut independently of body weight changes. Endocannabinoid tone and microbiome functionality at baseline drives an individualised response to an MD in ameliorating insulin sensitivity and inflammation. Clinical Trial Registry number and website NCT03071718; www.clinicaltrials.gov

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Nutritional intervention promoting Mediterranean diet improves dietary intake and enhances score adherence in adolescent athletes

Mediterranean Journal of Nutrition and Metabolism ◽

10.3233/mnm-200414 ◽

2020 ◽

Vol 13 (3) ◽

pp. 237-253

Author(s):

Rokia Sahnoune ◽

Malika Bouchenak

Keyword(s):

Mediterranean Diet ◽

Energy Intake ◽

Nutritional Intervention ◽

Fiber Intake ◽

Adequate Intake ◽

Total Proteins ◽

Adolescent Athletes ◽

24 Hour Recall ◽

The Impact ◽

Kidmed Index

BACKGROUND: Appropriate nutrition is important to maintain health, growth, and development of adolescent athlete performance. OBJECTIVE: To evaluate the impact of nutritional intervention (NI) promoting Mediterranean diet (MD), on food consumption, and adherence to MD, in scholar adolescent athletes. METHODS: Eighty athletes (Females/Males, 39/41) aged 15±1 years participated to NI. MD Adherence was assessed, using Kidmed index, at baseline, and at 6 months. Food intake was evaluated by 24-hour recall at baseline, and at four NI times. RESULTS: At baseline, 61% of athletes had poor MD adherence, and after NI, this value decreased to 10%. At 6 months of NI, 73% of males vs 46% of females had good MD adherence (≥8). Energy intake represented 2369 Kcal/d, at baseline, and was less than recommended value. After NI, significant increase was observed in energy intake (p = 0.001). Mean fiber intake (19 and 21 g/d in females and males, respectively) was less than adequate intake (26/38 g/d), but increased after NI (p = 0.000). Enhancement was noted in total, and complex carbohydrates, and total proteins, and values were increased with time (p = 0.000, p = 0.000, p = 0.003). CONCLUSION: Nutritional intervention, based on Mediterranean diet, improves total energy, and macronutrients intake, and increases MD adherence scores in adolescents athletes.

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Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial

EBioMedicine ◽

10.1016/j.ebiom.2021.103443 ◽

2021 ◽

Vol 69 ◽

pp. 103443

Author(s):

Brooke C. Wilson ◽

Éadaoin M. Butler ◽

Celia P. Grigg ◽

José G.B. Derraik ◽

Valentina Chiavaroli ◽

...

Keyword(s):

Caesarean Section ◽

Oral Administration ◽

Gut Microbiome ◽

Controlled Trial ◽

Microbiome Development

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Subcutaneous Oxyntomodulin Reduces Body Weight in Overweight and Obese Subjects: A Double-Blind, Randomized, Controlled Trial

Diabetes ◽

10.2337/diabetes.54.8.2390 ◽

2005 ◽

Vol 54 (8) ◽

pp. 2390-2395 ◽

Cited By ~ 287

Author(s):

K. Wynne ◽

A. J. Park ◽

C. J. Small ◽

M. Patterson ◽

S. M. Ellis ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Body Weight ◽

Controlled Trial ◽

Double Blind ◽

Randomized Controlled ◽

Obese Subjects

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Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial

Trials ◽

10.1186/s13063-021-05060-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Edward C. Deehan ◽

Eloisa Colin-Ramirez ◽

Lucila Triador ◽

Karen L. Madsen ◽

Carla M. Prado ◽

...

Keyword(s):

Insulin Resistance ◽

Randomized Controlled Trial ◽

Combination Therapy ◽

Gut Microbiome ◽

Controlled Trial ◽

Fecal Microbiota ◽

Metabolic Effects ◽

Microbiota Composition ◽

Randomized Controlled ◽

Secondary Outcomes

Abstract Background Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. Methods This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12–18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. Discussion This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. Trial registration ClinicalTrials.gov NCT04578652. Registered on 8 October 2020.

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Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

The ISME Journal ◽

10.1038/s41396-021-00998-8 ◽

2021 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Gut Microbiome ◽

Human Gut ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

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The Effects of Time-Restricted Eating versus Standard Dietary Advice on Weight, Metabolic Health and the Consumption of Processed Food: A Pragmatic Randomised Controlled Trial in Community-Based Adults

Nutrients ◽

10.3390/nu13031042 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1042

Author(s):

Nicholas Phillips ◽

Julie Mareschal ◽

Nathalie Schwab ◽

Emily Manoogian ◽

Sylvie Borloz ◽

...

Keyword(s):

Weight Loss ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Smartphone Application ◽

Metabolic Health ◽

Dietary Advice ◽

Processed Food ◽

Significant Difference ◽

Randomised Controlled ◽

Pragmatic Randomised Controlled Trial

Weight loss is key to controlling the increasing prevalence of metabolic syndrome (MS) and its components, i.e., central obesity, hypertension, prediabetes and dyslipidaemia. The goals of our study were two-fold. First, we characterised the relationships between eating duration, unprocessed and processed food consumption and metabolic health. During 4 weeks of observation, 213 adults used a smartphone application to record food and drink consumption, which was annotated for food processing levels following the NOVA classification. Low consumption of unprocessed food and low physical activity showed significant associations with multiple MS components. Second, in a pragmatic randomised controlled trial, we compared the metabolic benefits of 12 h time-restricted eating (TRE) to standard dietary advice (SDA) in 54 adults with an eating duration > 14 h and at least one MS component. After 6 months, those randomised to TRE lost 1.6% of initial body weight (SD 2.9, p = 0.01), compared to the absence of weight loss with SDA (−1.1%, SD 3.5, p = 0.19). There was no significant difference in weight loss between TRE and SDA (between-group difference −0.88%, 95% confidence interval −3.1 to 1.3, p = 0.43). Our results show the potential of smartphone records to predict metabolic health and highlight that further research is needed to improve individual responses to TRE such as a shorter eating window or its actual clock time.

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The Influence of Tart Cherry (Prunus cerasus, cv Montmorency) Concentrate Supplementation for 3 Months on Cardiometabolic Risk Factors in Middle-Aged Adults: A Randomised, Placebo-Controlled Trial

Nutrients ◽

10.3390/nu13051417 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1417

Author(s):

Rachel Kimble ◽

Karen M. Keane ◽

John K. Lodge ◽

Glyn Howatson

Keyword(s):

Vascular Function ◽

Controlled Trial ◽

High Sensitivity ◽

Metabolic Health ◽

Cardiometabolic Health ◽

Middle Aged ◽

Concentrate Supplementation ◽

Health Indices ◽

Before And After ◽

Middle Aged Adults

Background: Tart Montmorency cherries (MC) have been shown to be rich in anthocyanins and other phytochemicals known to have anti-inflammatory properties and influence pathways that might improve cardiometabolic health. However, there is limited evidence for the longer-term use of tart cherries on these indices. The aim of the current study was to investigate the influence of MC concentrate on cardiometabolic health indices following a 3-month supplementation period. Methods: Fifty middle-aged adults (34 males and 16 females; mean ± SD age: 48 ± 6 years and BMI: 27.6 ± 3.7 kg/m2) completed a randomised, placebo-controlled parallel study in which they either received MC or an isocaloric placebo. Participants drank 30 mL of their allocated treatment twice per day for 3 months. Vascular function (blood pressure [BP], heart rate [HR], pulse wave velocity and analysis [PWV/A], and flow mediated dilation [FMD]) as well as indices of metabolic health (insulin, glucose, lipid profiles, and high sensitivity C reactive protein) were measured following an overnight fast before and after the 3 months. Results: No effect of the intervention between the groups was observed for vascular function or metabolic health variables following the intervention (p > 0.05). However, MC concentrate was shown to be safe and well-tolerated and, importantly, did not have any deleterious effects on these outcomes. In conclusion, MC has no influence on cardiometabolic indices in middle-aged adults.

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