scholarly journals Timing of Calorie Restriction in Mice Impacts Host Metabolic Phenotype with Correlative Changes in Gut Microbiota

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Liying Zhang ◽  
Xinhe Xue ◽  
Rui Zhai ◽  
Xin Yang ◽  
Hui Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Calorie Restriction ◽  
Metabolic Phenotype ◽  
Intestinal Barrier Function ◽  
Calorie Intake ◽  
Feeding Time ◽  
Physiological Changes ◽  
Late Night ◽  
Ad Libitum ◽  
The Impact

ABSTRACT Calorie restriction (CR) is accompanied by self-imposed daily restriction of food intake and an extended fasting period between meals. The impact of restricting feeding to the dark or light phase on the effects of CR remains elusive. Here, light-fed CR mice showed physiological changes, such as muscle loss, concomitant with changes in the gut microbiota structure and composition. After switching to ad libitum access to food, light-fed mice had a period of food-craving behavior and short-lived physiological changes, while dark-fed mice displayed lasting changes in fat accumulation, glucose metabolism, intestinal barrier function, and systemic inflammatory markers. Moreover, the gut microbiota was modulated by when the food was consumed, and the most abundant Lactobacillus operational taxonomic unit (OTU) promoted by CR was enhanced in dark-fed mice. After switching to ad libitum feeding, the gut microbiota of dark-fed mice returned to the state resembling that of mice fed normal chow ad libitum, but that of light-fed mice was still significantly different from the other two groups. Together, these data indicate that for CR, restricting food consumption to the active phase brought better metabolic phenotype associated with potentially beneficial structural shifts in the gut microbiota. IMPORTANCE Aberrant feeding patterns whereby people eat more frequently throughout the day and with a bias toward late-night eating are prevalent in society today. However, whether restriction of food to daytime in comparison to nighttime, coupled with restricted calorie intake, can influence gut microbiota, metabolism, and overall health requires further investigation. We surveyed the effects of the shift in feeding time on gut microbiota and metabolic phenotype in calorie-restricted mice and found that avoiding eating during the rest period may generate more beneficial effects in mice. This work strengthens the evidence for using “when to eat” as an intervention to improve health during calorie restriction.

scholarly journals THE INFLUENCE OF LIFE-EXTENDING MUTATION AND DIETARY INTERVENTION ON GUT MICROBIOTA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S834-S834
Author(s):  
Michal Masternak ◽  
Denise S Wiesenborn ◽  
Augusto Schneider ◽  
Till Strowig ◽  
Karl –Herbert Schafer ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Calorie Restriction ◽  
Dietary Intervention ◽  
Ecological System ◽  
Gastrointestinal Microbiota ◽  
Age Related ◽  
Ames Dwarf ◽  
Feeding Regimen ◽  
Ad Libitum ◽  
The Impact

Abstract The gastrointestinal microbiota represents a large and complex ecological system of different microorganisms. Recently, there is an increasing interest in the impact of microbiota on development of different age-related diseases. We tested the changes of gut microbiota during development in long-living Ames dwarf (df/df) mice and we compared the effects of this life-extending mutation with the impact of calorie restriction (CR). Importantly, the analysis of microbiome showed significant differences in the ratio of Bacteroidetes and Firmicutes when comparing df/df and normal (N) mice (p<0.001). The LefSe analysis showed distinct microbiome distribution between CR and ad libitum (AL) feeding regimen in N animals (p<0.004), yet there was lack of similar changes in response to CR in df/df mice. In summary, our study showed significant genotype impact on gut microbiota and we showed that life-extending CR regimen provide divergent effects on gut microbiota in N when comparing with df/df mice.

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
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Health ◽  
Metabolic Phenotype ◽  
Intermittent Fasting ◽  
High Fat ◽  
Eating Pattern ◽  
Positive Effects ◽  
Normal Chow ◽  
Ad Libitum

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.

scholarly journals Gut Microbiota Composition and Predicted Microbial Metabolic Pathways of Obesity Prone and Obesity Resistant Outbred Sprague-Dawley CD Rats May Account for Differences in Their Phenotype

2021 ◽  
Vol 8 ◽  
Author(s):  
Diana N. Obanda ◽  
Michael J. Keenan ◽  
Ryan Page ◽  
Anne M. Raggio ◽  
Christopher M. Taylor ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Phase 1 ◽  
Alpha Diversity ◽  
Metabolic Phenotype ◽  
Calorie Intake ◽  
Microbiota Composition ◽  
Phase 2 ◽  
Sprague Dawley ◽  
Uncultured Bacterium ◽  
Gut Microbiota Composition

Like humans, outbred Sprague-Dawley CD rats exhibit a polygenic pattern of inheritance of the obese phenotype and not all individuals exposed to a high calorie intake develop obesity. We hypothesized that differences in gut microbiota composition account for phenotype differences between obese prone (OP) and obese resistant (OR) rats. We studied the gut microbiota composition of OPand OR rats after a high fat (HF) diet and how they respond to fermentation of resistant starch (RS). In phase 1 of the study 28 OP and 28 OR rats were fed a HF diet. In order to determine causal role of microbiota on phenotypes, In phase 2, a microbiota transplant between the two phenotypes was performed before switching all rats to a HF diet supplemented with 20% RS. We determined microbiota composition by 16S sequencing and predicted microbiota function by PICRUSt2. Despite a similar calorie intake, in phase 2 OP rats gained more weight and accumulated more abdominal fat in both phase 1 and 2 compared to OR rats (P < 0.001; n = 6). The OP rats fermented RS more robustly compared with OR rats with an increase in total bacteria, short chain fatty acids, and increased weight of the cecum, but microbiota of OP rats had much lower alpha diversity and evenness. The microbiota of OP rats, had higher amounts of bacteria from order Bacteroidales, specifically family Muribaculaceae (S24-7), which is known to possess several starch degrading enzymes and was reported in previous studies to increase with fermentation of RS. The OR rats fermented RS less but had higher bacterial diversity and evenness and had significantly higher bacterial counts from phylum Firmicutes particularly order Clostridiales, genus Clostridium and an uncultured bacterium of the genus Akkermansia. The microbiota of OR rats had enhanced bacterial chemotaxis, phosphotransferase system (PTS), and fatty acid biosynthesis compared to OP rats whose microbiota had higher glycan degradation and LPS biosynthesis pathways. The microbiota transplant did not change obesity phenotype or microbiota composition. In conclusion, a higher alpha-diversity and evenness of the microbiota and higher proportions of Clostridiales and Akkermansia in OR rats were associated with a better metabolic phenotype with lower body fat. However, robust RS fermentation caused a lower diversity and evenness and did not result in a leaner phenotype.

scholarly journals Metabolic Responses to Butyrate Supplementation in LF- and HF-Fed Mice Are Cohort-Dependent and Associated with Changes in Composition and Function of the Gut Microbiota

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3524
Author(s):  
Sunhye Lee ◽  
Trina A. Knotts ◽  
Michael L. Goodson ◽  
Mariana Barboza ◽  
Elyse Wudeck ◽  
...  
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
Feeding Behavior ◽  
Intestinal Permeability ◽  
Intestinal Inflammation ◽  
Metabolic Phenotype ◽  
Metabolic Responses ◽  
Intestinal Barrier Function ◽  
Fecal Microbiome ◽  
Beneficial Effects

The gut microbiota and associated metabolites have emerged as potential modulators of pathophysiological changes in obesity and related metabolic disorders. Butyrate, a product of bacterial fermentation, has been shown to have beneficial effects in obesity and rodent models of diet-induced obesity. Here, we aimed to determine the beneficial effects of butyrate (as glycerol ester of butyrate monobutyrin, MB) supplementation on metabolic phenotype, intestinal permeability and inflammation, feeding behavior, and the gut microbiota in low-fat (LF)- and high-fat (HF)-fed mice. Two cohorts (separated by 2 weeks) of male C57BL/6J mice (n = 24 in each cohort, 6/group/cohort; 6 weeks old) were separated into four weight-matched groups and fed either a LF (10 % fat/kcal) or HF (45% fat/kcal) with or without supplementation of MB (LF/MB or HF/MB) at 0.25% (w/v) in drinking water for 6 weeks. Metabolic phenotypes (body weight and adiposity), intestinal inflammation, feeding behavior, and fecal microbiome and metabolites were measured. Despite identical genetic and experimental conditions, we found marked differences between cohorts in the response (body weight gain, adiposity, and intestinal permeability) to HF-diet and MB. Notably, the composition of the gut microbiota was significantly different between cohorts, characterized by lower species richness and differential abundance of a large number of taxa, including subtaxa from five phyla, including increased abundance of the genera Bacteroides, Proteobacteria, and Parasutterella in cohort 2 compared to cohort 1. These differences may have contributed to the differential response in intestinal permeability to the HF diet in cohort 2. MB supplementation had no significant effect on metabolic phenotype, but there was a trend to protect from HF-induced impairments in intestinal barrier function in cohort 1 and in sensitivity to cholecystokinin (CCK) in both cohorts. These data support the concept that microbiota composition may have a crucial effect on metabolic responses of a host to dietary interventions and highlight the importance of taking steps to ensure reproducibility in rodent studies.

scholarly journals Cats reorganise their feeding behaviours when moving from ad libitum to restricted feeding

2020 ◽  
Vol 22 (10) ◽  
pp. 953-958
Author(s):  
Séverine Ligout ◽  
Xuemei Si ◽  
Hanne Vlaeminck ◽  
Sandra Lyn
Keyword(s):  
Calorie Restriction ◽  
Feeding Behaviour ◽  
Test Group ◽  
Feeding Strategies ◽  
Agonistic Interactions ◽  
Entire Study ◽  
Ad Libitum ◽  
The Impact ◽  
Ad Libitum Feeding ◽  
Feeding Behaviours

Objectives One identified solution to prevent obesity in cats is to control and limit their calorie intake. The objective of the present work was to better elucidate the impact of calorie cut-off on the feeding behaviour of cats. Methods A control (n = 31) and a test group of cats (n = 38) were included in the present study. Both groups received the same food variety during the study. A period of ad libitum feeding was initially set (T0), followed by a 9-month mild calorie restriction period for the test group only (T9; average calorie restriction = 6%), and a final period of ad libitum feeding (T10). The individual cat feeding behaviours were measured via an electronic feeding system, and agonistic interactions between cats during food anticipation via video observations. Generalised linear mixed models were fitted to compare all feeding parameters between periods by group. No statistical analyses could be performed on the agonistic interactions data owing to their structure. Results The feeding behaviour of the control group remained stable during the entire study, while the test group showed fewer but larger meals taken at shorter time intervals and a faster eating rate in response to calorie restriction. The average total number of agonistic interactions per cat increased during the calorie cut-off period in the test group only. One month after returning to ad libitum feeding, all behaviours were largely restored to baseline values. Conclusions and relevance Behavioural changes expressed by cats under calorie restriction can explain some of the difficulties obtaining cat owners’ compliance with dietary restriction, especially in multi-cat households. Feeding strategies should be utilised to help cats be less impulsive and maintain normal feeding patterns when moving away from ad libitum feeding.

scholarly journals Effects of Dietary Calorie Restriction or Exercise on the PI3K and Ras Signaling Pathways in the Skin of Mice

2007 ◽  
Vol 282 (38) ◽  
pp. 28025-28035 ◽  
Author(s):  
Linglin Xie ◽  
Yu Jiang ◽  
Ping Ouyang ◽  
Jie Chen ◽  
Hieu Doan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Fat ◽  
Calorie Restriction ◽  
Weight Control ◽  
Mapk Pathway ◽  
Subcutaneous Fat ◽  
Tumor Promoter ◽  
Calorie Intake ◽  
Ras Signaling ◽  
Ad Libitum

Weight control by exercise and dietary calorie restriction (DCR) has been associated with reduced cancer risk, but the underlying mechanisms are not well understood. This study was designed to compare the effects of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways. SENCAR mice were randomly assigned to one of the following five groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AL+Exe), exercise but pair-fed at the amount as controls (PF+Exe), 20% DCR, and 20% DCR plus exercise (DCR+Exe). After 10 weeks, body weight and body fat significantly decreased in the groups of DCR, DCR+Exe, and PF+Exe when compared with the controls. AL+Exe did not induce weight loss due to, at least in part, increased food intake. Plasma IGF-1 levels reduced significantly in DCR and DCR+Exe but not PF+Exe. The protein H-Ras and activated Ras-GTP significantly decreased in TPA-induced skin tissues of DCR-fed mice but not exercised mice. PI3K protein, phosphoserine Akt, and p42/p44-MAPK were reduced, however, in both DCR and PF+Exe groups. Immunohistochemistry demonstrated that the significantly reduced H-Ras occurred in subcutaneous fat cells, while the reduced PI3K and PCNA took place only in the epidermis. Plasma leptin decreased in PF+Exe, DCR, and DCR+Exe, while the caspase-3 activity increased in DCR+Exe only. Genomic microarray analysis further indicated that the expression of 34 genes relevant to PI3K and 31 genes to the MAPK pathway were significantly regulated by either DCR or PF+Exe treatments. The reduced PI3K in PF+Exe mice was partially reversed by IGF-1 treatment. The overall results of this study demonstrated that DCR abrogated both Ras and PI3K signaling, which might inhibit TPA-induced proliferation and anti-apoptosis. Selective inhibition of PI3K by PF+Exe but not AL+Exe seems more attributable to the magnitude of the caloric deficit and/or body fat loss than diet versus exercise comparison.

scholarly journals Adverse metabolic phenotype in low-birth-weight lambs and its modification by postnatal nutrition

2011 ◽  
Vol 107 (4) ◽  
pp. 510-522 ◽  
Author(s):  
Jacqueline M. Wallace ◽  
John S. Milne ◽  
Clare L. Adam ◽  
Raymond P. Aitken
Keyword(s):  
Birth Weight ◽  
Glucose Metabolism ◽  
Low Birth Weight ◽  
Fasting Glucose ◽  
Negative Relationship ◽  
Metabolic Phenotype ◽  
Gestation Length ◽  
Dietary Intakes ◽  
Ad Libitum ◽  
The Impact

Both high and low maternal dietary intakes adversely affect fetal nutrient supply in adolescent sheep pregnancies. Aims were: (a) to assess the impact of prenatal nutrition on pregnancy outcome, offspring growth and offspring glucose metabolism and (b) to determine whether the offspring metabolic phenotype could then be altered by modifying postnatal nutrition. Dams carrying a single fetus were offered either an optimal control (C) intake to maintain adiposity throughout pregnancy, undernourished to maintain weight at conception but deplete maternal reserves (UN), or overnourished to promote rapid maternal growth and adiposity (ON). Placental weight and gestation length were reduced in ON dams and lamb birth weights were C>UN>ON (P < 0·001). All offspring were fed ad libitum from weaning to 6 months of age. ON offspring exhibited rapid catch-up growth and had increased fasting glucose and relative glucose intolerance compared with C offspring (P < 0·05). Irrespective of prenatal diet and sex, birth weight correlated negatively with these indices of glucose metabolism. From 7 to 12 months offspring either had continued ad libitum diet (ADLIB; to induce an obesogenic state) or a decreased ration appropriate for normal growth (NORM). At 12 months, the negative relationship between birth weight and indices of glucose metabolism persisted in ADLIB females (for example, fasting glucose, r − 0·632; P < 0·03) but was absent in NORM females and in both male groups. Therefore, low-birth-weight offspring from differentially achieved prenatal malnutrition exhibit an early adverse metabolic phenotype, and this can apparently be ameliorated by postnatal nutrition in females but not in males.

Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice

Science ◽  
2020 ◽  
Vol 367 (6481) ◽  
pp. eaaw8429 ◽  
Author(s):  
Ikuo Kimura ◽  
Junki Miyamoto ◽  
Ryuji Ohue-Kitano ◽  
Keita Watanabe ◽  
Takahiro Yamada ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Dietary Habits ◽  
Developmental Process ◽  
Short Chain Fatty Acids ◽  
Metabolic Phenotype ◽  
Metabolic System ◽  
Postnatal Environment ◽  
The Impact

Antibiotics and dietary habits can affect the gut microbial community, thus influencing disease susceptibility. Although the effect of microbiota on the postnatal environment has been well documented, much less is known regarding the impact of gut microbiota at the embryonic stage. Here we show that maternal microbiota shapes the metabolic system of offspring in mice. During pregnancy, short-chain fatty acids produced by the maternal microbiota dictate the differentiation of neural, intestinal, and pancreatic cells through embryonic GPR41 and GPR43. This developmental process helps maintain postnatal energy homeostasis, as evidenced by the fact that offspring from germ-free mothers are highly susceptible to metabolic syndrome, even when reared under conventional conditions. Thus, our findings elaborate on a link between the maternal gut environment and the developmental origin of metabolic syndrome.

scholarly journals Longitudinal Analysis of the Intestinal Microbiota in the Obese Mangalica Pig Reveals Alterations in Bacteria and Bacteriophage Populations Associated With Changes in Body Composition and Diet

2021 ◽  
Vol 11 ◽  
Author(s):  
Haley A. Hallowell ◽  
Keah V. Higgins ◽  
Morgan Roberts ◽  
Robert M. Johnson ◽  
Jenna Bayne ◽  
...  
Keyword(s):  
Body Composition ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
High Fat Diet ◽  
Metabolic Phenotype ◽  
Oral Glucose ◽  
Standard Diet ◽  
High Fat ◽  
Metabolic Complications ◽  
Ad Libitum

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.

scholarly journals A More Robust Gut Microbiota in Calorie-Restricted Mice Is Associated with Attenuated Intestinal Injury Caused by the Chemotherapy Drug Cyclophosphamide

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Tao Liu ◽  
Yanqiu Wu ◽  
Linghua Wang ◽  
Xiaoyan Pang ◽  
Liping Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Side Effects ◽  
Gut Microbiota ◽  
Cancer Chemotherapy ◽  
Calorie Restriction ◽  
Bacterial Translocation ◽  
Epithelial Stem Cells ◽  
Gut Barrier Function ◽  
Potential Benefits ◽  
Ad Libitum

ABSTRACTCyclophosphamide (CTX) is widely used in cancer chemotherapy, but it often induces mucositis, in which the disruption of the gut microbiota might play a pivotal role. Whether the manipulation of the gut microbiota can be used as a strategy to improve CTX-induced mucositis remains to be studied. Here we observed the effects of a 4-week calorie restriction (CR) on CTX-induced mucositis. Compared withad libitum-fed mice, CR mice showed significantly less mucositis in response to CTX, including lower intestinal permeability, less bacterial translocation, higher number of epithelial stem cells, and less epithelium damage. CTX induced significant shifts of the gut microbiota of the gut microbiota inad libitum-fed control mice. In contrast, CR mice showed no significant change in their gut microbiota in responding to CTX treatment. CR significantly enriched the gut microbiota inLactobacillusandLachnospiraceaewhich are known to mitigate inflammation and improve gut barrier function. These findings suggest that CR remodeled gut microbiota is more robust and may contribute to attenuate the side effects of cyclophosphamide, which supports the concept that cancer chemotherapy would benefit from strategies targeting the gut microbiota.IMPORTANCEImproving the gut microbiota via calorie restriction is beneficial for human health. Our findings showed differential responses between calorie-restricted mice andad libitum-fed mice. Compared with thead libitum-fed mice, the calorie-restricted mice were less susceptible to cyclophosphamide side effects otherwise observed on the gut integrity and its microbiota. These results show the potential benefits of manipulating the gut microbiota with CR prior to cancer chemotherapy.

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