scholarly journals The effect of calorie intake, fasting, and dietary composition on metabolic health and gut microbiota in mice

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziyi Zhang ◽  
Xiaoyu Chen ◽  
Yuh Jiun Loh ◽  
Xin Yang ◽  
Chenhong Zhang

Abstract Background Calorie restriction (CR) and intermittent fasting (IF) can promote metabolic health through a process that is partially mediated by gut microbiota modulation. To compare the effects of CR and IF with different dietary structures on metabolic health and the gut microbiota, we performed an experiment in which mice were subjected to a CR or IF regimen and an additional IF control (IFCtrl) group whose total energy intake was not different from that of the CR group was included. Each regimen was included for normal chow and high-fat diet. Results We showed that in normal-chow mice, the IFCtrl regimen had similar positive effects on glucose and lipid metabolism as the CR regimen, but the IF regimen showed almost no influence compared to the outcomes observed in the ad libitum group. IF also resulted in improvements, but the effects were less marked than those associate with CR and IFCtrl when the mice were fed a high-fat diet. Moreover, CR created a stable and unique gut microbial community, while the gut microbiota shaped by IF exhibited dynamic changes in fasting-refeeding cycles. At the end of each cycle, the gut microbiota of the IFCtrl mice was similar to that of the CR mice, and the gut microbiota of the IF mice was similar to that of the ad libitum group. When the abundance of Lactobacillus murinus OTU2 was high, the corresponding metabolic phenotype was improved regardless of eating pattern and dietary structure, which might be one of the key bacterial groups in the gut microbiota that is positively correlated with metabolic amelioration. Conclusion There are interactions among the amount of food intake, the diet structure, and the fasting time on metabolic health. The structure and composition of gut microbiota modified by dietary regimens might contribute to the beneficial effects on the host metabolism.

Author(s):  
Sik Yu So ◽  
Qinglong Wu ◽  
Kin Sum Leung ◽  
Zuzanna Maria Kundi ◽  
Tor C Savidge ◽  
...  

Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-week dietary supplementation in healthy mice to evaluate effects of different fiber composition (soluble vs particulate Y-BG) and dose (0.1 vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver Cyp7a1 mRNA abundance and bile acid synthesis. These diet-induced responses were notably different when compared to the prebiotic inulin, and included a marked reduction in fecal Bilophila abundance which we demonstrated as translatable to obesity in population-scale American Gut and TwinsUK clinical cohorts. This prompted us to test whether 2% Y-BG maintained metabolic health in mice fed 60% HFD over 13 weeks. Y-BG consistently altered the gut microbiota composition and reduced Bilophila abundance, with trends observed in improvement of metabolic phenotype. Notably, Y-BG improved insulin sensitization and this was associated with enhanced ileal Glpr1r mRNA accumulation and reduced Bilophila abundance. Collectively, our results demonstrate that Y-BG modulates gut microbiota community composition and bile acid signaling, but the dietary regime needs to be optimized to facilitate clinical improvement in metabolic phenotype in an aggressive high-fat diet animal model.


Author(s):  
Haley A. Hallowell ◽  
Keah V. Higgins ◽  
Morgan Roberts ◽  
Robert M. Johnson ◽  
Jenna Bayne ◽  
...  

Due to its immunomodulatory potential, the intestinal microbiota has been implicated as a contributing factor in the development of the meta-inflammatory state that drives obesity-associated insulin resistance and type 2 diabetes. A better understanding of this link would facilitate the development of targeted treatments and therapies to treat the metabolic complications of obesity. To this end, we validated and utilized a novel swine model of obesity, the Mangalica pig, to characterize changes in the gut microbiota during the development of an obese phenotype, and in response to dietary differences. In the first study, we characterized the metabolic phenotype and gut microbiota in lean and obese adult Mangalica pigs. Obese or lean groups were created by allowing either ad libitum (obese) or restricted (lean) access to a standard diet for 54 weeks. Mature obese pigs were significantly heavier and exhibited 170% greater subcutaneous adipose tissue mass, with no differences in muscle mass compared to their lean counterparts. Obese pigs displayed impaired glucose tolerance and hyperinsulinemia following oral glucose challenge, indicating that a metabolic phenotype also manifested with changes in body composition. Consistent with observations in human obesity, the gut microbiota of obese pigs displayed altered bacterial composition. In the second study, we characterized the longitudinal changes in the gut microbiota in response to diet and aging in growing Mangalica pigs that were either limit fed a standard diet, allowed ad libitum access to a standard diet, or allowed ad libitum access to a high fat-supplemented diet over an 18-week period. As expected, weight gain was highest in pigs fed the high fat diet compared to ad libitum and limit fed groups. Furthermore, the ad libitum and high fat groups displayed significantly greater adiposity consistent with the development of obesity relative to the limit fed pigs. The intestinal microbiota was generally resilient to differences in dietary intake (limit fed vs ad libitum), though changes in the microbiota of pigs fed the high fat diet mirrored changes observed in mature obese pigs during the first study. This is consistent with the link observed between the microbiota and adiposity. In contrast to intestinal bacterial populations, bacteriophage populations within the gut microbiota responded rapidly to differences in diet, with significant compositional changes in bacteriophage genera observed between the dietary treatment groups as pigs aged. These studies are the first to describe the development of the intestinal microbiota in the Mangalica pig, and are the first to provide evidence that changes in body composition and dietary conditions are associated with changes in the microbiome of this novel porcine model of obesity.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Wong ◽  
Rafael de Cabo ◽  
Michel Bernier ◽  
Alberto Diaz-Ruiz ◽  
Tyler Rhinesmith ◽  
...  

Abstract Objectives 4:10 periodic fasting schedule is proposed to improve biomarkers of healthspan through metabolic flexibility in mice on both standard and high fat diets. Methods Our study adopted the 4:10 fasting schedule using the fasting-mimicking diet (FMD) as our model. FMD is a plant-based, low-protein, and low-sugar diet regime implemented for four days every two-week cycle. Its regenerative effect is observed in the refeeding phase following starvation, allowing for the breakdown of cells via increased autophagy. In comparison to stricter fasting regimes such as intermittent fasting, chronic caloric restriction, and periodic fasting, FMD is well-tolerated in the clinical setting. 74 12-month old C57BL/6 mice were randomized into two diet groups: standard diet or high-fat diet. For 4 days out of every fourteen days, the mice were severely caloric restricted and refed with ad-libitum of either standard or high fat diets for the remaining 10 days, matching the controls who were fixed on the ad-libitum diet. The 4:10 fasting schedule was repeated 11 times before the mice were sacrificed. To measure metabolic flexibility, metabolic cages, ELISA, and glucose meters were used. Results Body weight and composition, metabolic flexibility, and insulin sensitivity indicate differences between fasting on diet composition. Not only did those on the fasting high-fat diet (FHFD) remain overweight, identical to their HFD controls, insulin sensitivity was also attenuated in FHFD groups. Fasting standard diet (FSD) had a reduction of 5% in body weight and 15% in body fat. Carbohydrate and lipid metabolism differences indicated by the respiratory exchange ratio as well as motor function performance differences further support the positive impact of fasting on SD groups, not HFD groups. Characteristic of positive healthspan biomarkers, reduced leptin and improved insulin sensitivity was observed with FSD, not FHFD. Conclusions We found that while the FMD schedule improved healthspan as indicated by biomarkers of healthy aging for mice on the standard diet, it could not counteract the negative health effects of the obesogenic diet. These results demonstrate the importance of not only time of feeding but also diet composition in respect to healthspan. Funding Sources National Institute on Aging (NIA) – National Institutes of Health (NIH).


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2188 ◽  
Author(s):  
Ning-Ning Zhang ◽  
Wen-Hui Guo ◽  
Han Hu ◽  
A-Rong Zhou ◽  
Qing-Pei Liu ◽  
...  

This study investigated the influence of Canarium album extract (CAext) on intestinal microbiota composition of mice fed a high-fat diet (HFD). Kun Ming (KM) mice were fed either a normal chow diet or a HFD for six weeks. At the seventh week, HFD-fed mice were gavaged daily with saline, or a different dose of CAext for four weeks, respectively. Then, the composition of the gut microbiota was analyzed by high-throughput sequencing technology. Analysis of fecal microbial populations, grouped by phyla, showed significant increases of Firmicutes and Verrucomicrobia, but a decrease of Bacteroidetes in all CAext-fed mice. Particularly, CAext gavage in a low dose or a medium dose caused a significant increase in the proportion of Akkermansia. These findings suggested that CAext can alter the gut microbiota composition of HFD-fed mice, and had a potential prebiotic effects on Akkermansia.


2021 ◽  
Vol 53 (9) ◽  
pp. 1298-1306
Author(s):  
Dandan Wu ◽  
In Hyuk Bang ◽  
Byung-Hyun Park ◽  
Eun Ju Bae

AbstractIntermittent fasting (IF) is gaining popularity for its effectiveness in improving overall health, including its effectiveness in achieving weight loss and euglycemia. The molecular mechanisms of IF, however, are not well understood. This study investigated the relationship between adipocyte sirtuin 6 (Sirt6) and the metabolic benefits of IF. Adipocyte-specific Sirt6-knockout (aS6KO) mice and wild-type littermates were fed a high-fat diet (HFD) ad libitum for four weeks and then subjected to 12 weeks on a 2:1 IF regimen consisting of two days of feeding followed by one day of fasting. Compared with wild-type mice, aS6KO mice subjected to HFD + IF exhibited a diminished response, as reflected by their glucose and insulin intolerance, reduced energy expenditure and adipose tissue browning, and increased inflammation of white adipose tissue. Sirt6 deficiency in hepatocytes or in myeloid cells did not impair adaptation to IF. Finally, the results indicated that the impaired adipose tissue browning and reduced expression of UCP1 in aS6KO mice were accompanied by downregulation of p38 MAPK/ATF2 signaling. Our findings indicate that Sirt6 in adipocytes is critical to obtaining the improved glucose metabolism and metabolic profiles conferred by IF and that maintaining high levels of Sirt6 in adipocytes may mimic the health benefits of IF.


Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 456
Author(s):  
Mihai V. Curtasu ◽  
Valeria Tafintseva ◽  
Zachary A. Bendiks ◽  
Maria L. Marco ◽  
Achim Kohler ◽  
...  

The metabolome and gut microbiota were investigated in a juvenile Göttingen minipig model. This study aimed to explore the metabolic effects of two carbohydrate sources with different degrees of risk in obesity development when associated with a high fat intake. A high-risk (HR) high-fat diet containing 20% fructose was compared to a control lower-risk (LR) high-fat diet where a similar amount of carbohydrate was provided as a mix of digestible and resistant starch from high amylose maize. Both diets were fed ad libitum. Non-targeted metabolomics was used to explore plasma, urine, and feces samples over five months. Plasma and fecal short-chain fatty acids were targeted and quantified. Fecal microbiota was analyzed using genomic sequencing. Data analysis was performed using sparse multi-block partial least squares regression. The LR diet increased concentrations of fecal and plasma total short-chain fatty acids, primarily acetate, and there was a higher relative abundance of microbiota associated with acetate production such as Bacteroidetes and Ruminococcus. A higher proportion of Firmicutes was measured with the HR diet, together with a lower alpha diversity compared to the LR diet. Irrespective of diet, the ad libitum exposure to the high-energy diets was accompanied by well-known biomarkers associated with obesity and diabetes, particularly branched-chain amino acids, keto acids, and other catabolism metabolites.


2020 ◽  
Author(s):  
Yuqian Ye ◽  
Haopeng Xu ◽  
Zhibo Xie ◽  
Lun Wang ◽  
Yuning Sun ◽  
...  

Abstract Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism. Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints. Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p<0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p<0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes. Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.


2020 ◽  
Vol 7 ◽  
Author(s):  
Yuqian Ye ◽  
Haopeng Xu ◽  
Zhibo Xie ◽  
Lun Wang ◽  
Yuning Sun ◽  
...  

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism.Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints.Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p &lt; 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p &lt; 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes.Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1199-1199
Author(s):  
Theresa Bushman ◽  
Te-Yueh Lin ◽  
Xiaoli Chen

Abstract Objectives Extracellular vesicles (EVs), especially exosomes, have emerged as a critical regulator of intercellular and inter-organ communications. Dysregulation of exosome secretion and exosomal cargo composition has been associated with metabolic diseases. The objective of this study was to determine the effect of intermittent fasting (IF) on the size profile and cargoes of exosomes in diet-induced obesity. Methods Female and male mice (8–10 weeks old) were fed a high-fat diet (HFD) for 18 weeks prior to being placed either in an ad libitum feeding group (HFD-AL) or an IF feeding group (HFD-IF) for an additional 10 weeks. Mice on the normal chow ad libitum (NC-AL) for 28 weeks served as control. The IF group had food available for 10 hours and fasted for 14 hours daily. Serum EVs measured using Nanoparticle Tracking Analysis. Results HFD-AL mice had an increasing trend in mean diameter of serum EVs by 24 nm (P = 0.30) compared to the NC-AL mice. The IF caused a significant decrease in mean diameter of serum EVs by 47.9 nm (P &lt; 0.03) when compared to the HFD-AL mice. However, neither HFD nor IF altered the overall particle amount per mL of serum when compared to NC-AL. The HFD-AL mice had a decreasing trend in the population of small-size EVs but an increase in large-size EVs compared to the NC-AL mice. Mice on long-term HFD with IF had a significant increase in the total amount of small EVs/exosomes (50–100 nm in size) per unit of serum, but a decrease in the amount of large EVs (250–500 nm in size). Moreover, the mean population (particles/ml) of small EVs/exosomes were increased in the HFD-IF mice by an average of 38% (P &lt; 0.03), whereas the population of large-size micro-vesicles (250–300 nm in size) were decreased by an average of 4% (P &lt; 0.01) when compared to the HFD-AL mice. In addition to exosome alterations, the weekly weigh-in differences were significantly higher in the HFD-IF mice compared to the HFD-AL mice (P &lt; 0.02). Lastly, we found that IF could prevent the whitening of brown adipose tissue (BAT) and liver micro-vesicular steatosis induced by a long-term HFD. Conclusions IF significantly alters the profile of serum EVs, which may serve as an important mechanism for the metabolic benefits of IF such as preventing the whitening of BAT and liver micro-vesicular steatosis in obesity. Funding Sources This work was supported by the General Mills Foundation Chair in Genomics for Healthful Foods to X.C.


mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Xiaoyu Gao ◽  
Songlin Chang ◽  
Shuangfeng Liu ◽  
Lei Peng ◽  
Jing Xie ◽  
...  

ABSTRACT Previous studies have shown that α-linolenic acid (ALA) has a significant regulatory effect on related disorders induced by high-fat diets (HFDs), but little is known regarding the correlation between the gut microbiota and disease-related multitissue homeostasis. We systematically investigated the effects of ALA on the body composition, glucose homeostasis, hyperlipidemia, metabolic endotoxemia and systemic inflammation, white adipose tissue (WAT) homeostasis, liver homeostasis, intestinal homeostasis, and gut microbiota of mice fed an HFD (HFD mice). We found that ALA improved HFD-induced multitissue metabolic disorders and gut microbiota disorders to various degrees. Importantly, we established a complex but clear network between the gut microbiota and host parameters. Several specific differential bacteria were significantly associated with improved host parameters. Rikenellaceae_RC9_gut_group and Parasutterella were positively correlated with HFD-induced “harmful indicators” and negatively correlated with “beneficial indicators.” Intriguingly, Bilophila showed a strong negative correlation with HFD-induced multitissue metabolic disorders and a significant positive correlation with most beneficial indicators, which is different from its previous characterization as a “potentially harmful genus.” Turicibacter might be the key beneficial bacterium for ALA-improved metabolic endotoxemia, while Blautia might play an important role in ALA-improved gut barrier integrity and anti-inflammatory effects. The results suggested that the gut microbiota, especially some specific bacteria, played an important role in the process of ALA-improved multitissue homeostasis in HFD mice, and different bacteria might have different divisions of regulation. IMPORTANCE Insufficient intake of n-3 polyunsaturated fatty acids is an important issue in modern Western-style diets. A large amount of evidence now suggests that a balanced intestinal microecology is considered an important part of health. Our results show that α-linolenic acid administration significantly improved the host metabolic phenotype and gut microbiota of mice fed a high-fat diet, and there was a correlation between the improved gut microbiota and metabolic phenotype. Some specific bacteria may play a unique regulatory role. Here, we have established correlation networks between gut microbiota and multitissue homeostasis, which may provide a new basis for further elucidating the relationship between the gut microbiota and host metabolism.


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