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Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity.

ABSTRACT: Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.

SUBMITTER: Mohr AE

PROVIDER: S-EPMC9644216 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity.

Mohr Alex E AE Jasbi Paniz P Bowes Devin A DA Dirks Blake B Whisner Corrie M CM Arciero Karen M KM Poe Michelle M Gu Haiwei H Gumpricht Eric E Sweazea Karen L KL Arciero Paul J PJ

Frontiers in nutrition 20221026

Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-con ...[more]

PMID: 36386914

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Project description:BackgroundIntermittent fasting (IF), consisting of either a one-day (IF1) or two consecutive days (IF2) per week, is commonly used for optimal body weight loss. Our laboratory has previously shown an IF1 diet combined with 6d/week of protein pacing (P; 4-5 meals/day evenly spaced, ~ 30% protein/day) significantly enhances weight loss, body composition, and cardiometabolic health in obese men and women. Whether an IF1-P or IF2-P, matched for weekly energy intake (EI) and expenditure (EE), is superior for weight loss, body composition, and cardiometabolic health is unknown.MethodsThis randomized control study directly compared an IF1-P (n = 10) versus an IF2-P (n = 10) diet on weight loss and body composition, cardiovascular (blood pressure and lipids), hormone, and hunger responses in 20 overweight men and women during a 4-week weight loss period. Participants received weekly dietary counseling and monitoring of compliance from a registered dietitian. All outcome variables were assessed pre (week 0) and post (week 5).ResultsBoth groups significantly reduced body weight, waist circumference, percent body fat, fat mass, hunger, blood pressure, lipids, glucose, and increased percent fat-free mass (p < 0.05). However, IF2-P resulted in significantly greater reductions in body weight (-29%) and waist circumference (-38%) compared to IF1-P (p < 0.05), and showed a strong tendency for greater reductions in fat mass, glucose, and hunger levels (p < 0.10) despite similar weekly total EI (IF1-P, 9058 ± 692 vs. IF2-P, 8389 ± 438 kcals/week; p = 0.90), EE (~ 300 kcals/day; p = 0.79), and hormone responses (p > 0.10).ConclusionsThese findings support short-term IF1-P and IF2-P to optimize weight loss and improve body composition, cardiometabolic health, and hunger management, with IF2-P providing enhanced benefits in overweight women and men.Trial registrationThis trial was registered March 03, 2020 at www.Clinicaltrialsgov as NCT04327141 .

Project description:Clinical trials have demonstrated the health benefits of intermittent fasting (IF). However, the potential mechanism of IF in alleviating dextran sulfate sodium (DSS)-induced colitis is not fully understood. The present study was mainly designed to explore the dynamic changes in the gut microbiota and metabolome after short-term (2 weeks) or long-term (20 weeks) IF and therefore clarify the potential mechanisms by which IF ameliorates DSS-induced colitis in a murine model. Thirty-two C57BL/6 male mice were equally divided into four groups and underwent IF intervention for 2 weeks (SIF group, n = 8), 20 weeks (LIF group, n = 8), or were allowed free access to food for 2 weeks (SAL group, n = 8) or 20 weeks (LAL group, n = 8). The thirty-two C57BL/6 male mice were accepted for the diet intervention of 2 weeks of IF or fed ad libitum. Colitis was induced by drinking 2% DSS for 7 days. Our findings showed that short-term IF prominently elevates the abundance of Bacteroides, Muibaculum and Akkermansia (p < 0.001, p < 0.001, p < 0.001, respectively), and decreased the abundance of Ruminiclostridium (p < 0.05). Long-term IF, however, decreased the abundance of Akkermansia and obviously increased the abundance of Lactobacillus (p < 0.05, p < 0.001, respectively). Metabolites mainly associated with nucleoside, carbohydrate, amino acid, bile acid, fatty acid, polyol, steroid and amine metabolism were identified in the faeces using untargeted GC/MS. In particular, inosine was extremely enriched after short-term IF and long-term IF (p < 0.01, p < 0.01, respectively); butyrate, 2-methyl butyric acid and valeric acid were significantly decreased after short-term IF (p < 0.001, p < 0.001, p < 0.01, respectively); and 2-methyl butyric acid was significantly increased after long-term IF (p < 0.001). The abundance of lithocholic acid (LCA), one of the secondary bile acids, increased significantly after short-term and long-term IF based on UPLC-MS/MS (p < 0.001, p < 0.5, respectively). Of note, IF markedly mitigated DSS-induced acute colitis symptoms and down-regulated pro-inflammatory cytokines IL-1α, IL-6, keratinocyte-derived chemokine (KC) and G-CSF levels in the serum (p < 0.01, p < 0.001, p < 0.05, p < 0.001, respectively). Furthermore, a correlation analysis indicated that the disease activity index (DAI) score and serum levels of IL-1α, IL-6, KC, and G-CSF were negatively correlated with the relative abundance of Akkermansia and the faecal metabolites LCA and inosine. This study confirmed that IF altered microbiota and reprogramed metabolism, which was a promising development in the attempt to prevent DSS-induced colitis. Moreover, our findings provide new insights regarding the correlations among the mucosal barrier dysfunction, metabolome, and microbiome.

Project description:BackgroundIntermittent fasting is a popular dietary intervention with perceived relatively easy compliance and is linked to various health benefits, including weight loss and improvement in blood glucose concentrations. The mechanistic explanations underlying the beneficial effects of intermittent fasting remain largely obscure but may involve alterations in the gut microbiota.ObjectivesWe sought to establish the effects of 1 mo of intermittent fasting on the gut microbiome.MethodsWe took advantage of intermittent fasting being voluntarily observed during the Islamic faith-associated Ramadan and sampled feces and blood, as well as collected longitudinal physiologic data in 2 cohorts, sampled in 2 different years. The fecal microbiome was determined by 16S sequencing. Results were contrasted to age- and body weight-matched controls and correlated to physiologic parameters (e.g., body mass and calorie intake).ResultsWe observed that Ramadan-associated intermittent fasting increased microbiome diversity and was specifically associated with upregulation of the Clostridiales order-derived Lachnospiraceae [no fasting 24.6 ± 13.67 compared with fasting 39.7 ± 15.9 in relative abundance (%); linear discriminant analysis = 4.9, P < 0.001 by linear discriminant analysis coupled with effect size measurements] and Ruminococcaceae [no fasting 13.4 ± 6.9 compared with fasting 23.2 ± 12.9 in relative abundance (%); linear discriminant analysis = 4.7, P < 0.001 by linear discriminant analysis coupled with effect size measurements] bacterial families. Microbiome composition returned to baseline upon cessation of intermittent feeding. Furthermore, changes in Lachnospiraceae concentrations mirrored intermittent fasting-provoked changes in physiologic parameters.ConclusionsIntermittent fasting provokes substantial remodeling of the gut microbiome. The intermittent fasting-provoked upregulation of butyric acid-producing Lachnospiraceae provides an obvious possible mechanistic explanation for health effects associated with intermittent fasting.

Project description:Aim and backgroundA growing body of evidence supports the impact of intermittent fasting (IF) on normalizing body weight and that the interaction between body genes and environmental factors shapes human susceptibility to developing obesity. FTO gene is one of these genes with metabolic effects related to energy metabolism and body fat deposition. This research examined the changes in FTO gene expression upon Ramadan intermittent fasting (RIF) in a group of metabolically healthy subjects with overweight and obesity.MethodsSixty-three (63) subjects were recruited, of which 57 (17 males and 40 females, mean age 38.4 ± 11.2 years) subjects with overweight and obesity (BMI = 29.89 ± 5.02 kg/m2were recruited and monitored before and at the end of Ramadan month), and 6 healthy subjects with normal BMI (21.4 ± 2.20 kg/m2) recruited only to standardize the reference for normal levels of FTO gene expression. In the two-time points, anthropometric, biochemical, and dietary assessments were undertaken, and FTO gene expression tests were performed using RNA extracted from the whole blood sample.ResultsIn contrast to normal BMI subjects, the relative gene expressions in overweight/obese were significantly decreased at the end of Ramadan (-32.30%, 95% CI-0.052 -0.981) in comparison with the pre-fasting state. Significant reductions were found in body weight, BMI, fat mass, body fat percent, hip circumference, LDL, IL-6, TNF-α (P<0.001), and in waist circumference (P<0.05), whilst HDL and IL-10 significantly increased (P<0.001) at the end of Ramadan in comparison with the pre-fasting levels. Binary logistic regression analysis for genetic expressions showed no significant association between high-energy intake, waist circumference, or obesity and FTO gene expression.ConclusionsRIF is associated with the downregulation of the FTO gene expression in subjects with obesity, and this may explain, at least in part, its favorable metabolic effects. Hence, RIF presumably may entail a protective impact against body weight gain and its adverse metabolic-related derangements in subjects with obesity.

Project description:BackgroundOverweight and obesity among adults are a growing global public health threat and an essential risk factor for various noncommunicable diseases. Although intermittent fasting is a generally new dietary approach to weight management that has been increasingly practiced worldwide, the effectiveness of 2 days per week dry fasting remains unclear.ObjectiveThe Cardiometabolic and Anthropometric Outcomes of Intermittent Fasting study aims to determine the cardiometabolic, anthropometric, dietary intake, and quality of life changes among civil servants with overweight and obesity, following combined intermittent fasting and healthy plate (IFHP) and healthy plate (HP) and explore the participants' experiences.MethodsWe designed a mixed methods quasi-experimental study to evaluate the effectiveness of the IFHP and HP methods among adults with overweight and obesity. A total of 177 participants were recruited for this study, of which 91 (51.4%) were allocated to the IFHP group and 86 (48.6%) to the HP group. The intervention comprised 2 phases: supervised (12 weeks) and unsupervised (12 weeks). Data collection was conducted at baseline, after the supervised phase (week 12), and after the unsupervised phase (week 24). Serum and whole blood samples were collected from each participant for analysis. Data on sociodemographic factors, quality of life, physical activity, and dietary intake were also obtained using questionnaires during data collection.ResultsMost of the participants were female (147/177, 83.1%) and Malay (141/177, 79.7%). The expected outcomes of this study are changes in body weight, body composition, quality of life, physical activity, dietary intake, and cardiometabolic parameters such as fasting blood glucose, 2-hour postprandial blood glucose, hemoglobin A1c, fasting insulin, and lipid profile.ConclusionsThe Cardiometabolic and Anthropometric Outcomes of Intermittent Fasting study is a mixed methods study to evaluate the effectiveness of combined IFHP and HP interventions on cardiometabolic and anthropometric parameters and explore participants' experiences throughout the study.Trial registrationClinicalTrials.gov NCT05034653; https://clinicaltrials.gov/ct2/show/NCT05034653.International registered report identifier (irrid)RR1-10.2196/33801.

Project description:IntroductionDuring the holy month of Ramadan, adult healthy Muslims are mandated to abstain from dawn to sunset, with free eating at night hours that may extend up to 12 h. The current work was designed to investigate the metabolomics changes incurred upon the observance of Ramadan diurnal intermittent fasting (RDIF).MethodsTwenty-five metabolically healthy participants with overweight and obesity (7 females and 18 males, with a mean age of 39.48 ± 10.0 years) were recruited for the study and were followed before and at the end of RDIF month. Dietary, anthropometric, biochemical, and physical activity assessments were performed before and at the end of the fasting month. The metabolomic assay was performed using liquid chromatography-mass spectrometry for the two-time points.Results and discussionMetabolomics assay revealed a significant reduction in a few metabolites. The analysis revealed that 27 metabolites differed significantly (P < 0.05) between pre-and post-RDIF. Among the differentially abundant metabolites, 23 showed a decrease with fasting, these included several amino acids such as aspartame, tryptophan, phenylalanine, histidine, and other metabolites including valeric acid, and cortisol. On the other hand, only four metabolites showed increased levels after RDIF including traumatic acid, 2-pyrrolidinone, PC[18:1(9Z)/18:1(9Z)], and L-sorbose. The MetaboAnalyst® platform reported that the top enriched metabolic pathways included: (1) histidine metabolism; (2) folate biosynthesis (3) phenylalanine, tyrosine, and tryptophan biosynthesis; (4) aminoacyltRNA biosynthesis; (5) caffeine metabolism; (6) vitamin B6 metabolism; and several other pathways relating to lipid metabolisms such as arachidonic acid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In conclusion, RDIF entails significant changes in various metabolic pathways that reflect different dietary and lifestyle behaviors practiced during the fasting month.

Project description:Much research has been conducted regarding the impact of diet on the gut microbiota. However, the effects of dietary habits such as intermittent fasting are unclear. This study aimed to investigate the effect of intermittent fasting during Ramadan on the gut microbiota. The study was conducted on 12 healthy adult individuals who practiced fasting 17 h per day for 29 consecutive days during the month of Ramadan. To determine the dietary intake of individuals, a 3-day dietary record was kept at the beginning and end of the study. Reads that passed quality filtering were clustered, and custom-prepared 16S rRNA gene regions of bacteria associated with the human microbiome were used as a reference. Consensus sequences were created, and genus-level taxonomic annotations were determined using a sequence identity threshold of 95%. The correlations between the dietary intake measurements of the participants and the respective relative abundance of bacterial genera were investigated. The results showed that Firmicutes were higher in abundance in the gut microbiota before fasting among participants, while they were significantly lower in abundance at the end of Ramadan fasting (p < 0.05). Proteobacteria were significantly higher in abundance at the end of the month of Ramadan (p < 0.05). Fasting was associated with a significant decrease in levels of seven genera: Blautia, Coprococcus, Dorea, Faecalicatena, Fusicatenibacter, Lachnoclostridium, and Mediterraneibacter. Conversely, the abundances of two bacterial genera were enhanced at the end of the fasting month: Escherichia and Shigella. The results of the dietary intake analysis showed that a negative correlation was detected for three comparisons: Ihubacter and protein (rho = -0.54, p = 0.0068), Fusicatenibacter and vegetables (rho = -0.54, p = 0.0042), and Intestinibacter and nuts (rho = -0.54, p-value = 0.0065). The results suggest that even when the fasting period during Ramadan is consistent, the types of food consumed by individuals can affect the gut microbiota.

Dataset Information

Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity.

Publications

Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity.

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