Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota

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.

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Intermittent Fasting Alleviates Diabetes-induced Cognitive Decline via Gut Microbiota-metabolites-brain Axis (OR32-04-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz052.or32-04-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 2

Author(s):

Zhigang Liu ◽

Tian Yuan ◽

Xiaoshuang Dai ◽

Lin Shi ◽

Xuebo Liu

Keyword(s):

Cognitive Function ◽

Gut Microbiota ◽

Cognitive Decline ◽

Critical Role ◽

Development Program ◽

Plasma Metabolites ◽

Intermittent Fasting ◽

Metabolic Function ◽

Behavioral Tests ◽

Omics Analysis

Abstract Objectives Cognitive decline is one of severe type 2 diabetes complications. Intermittent fasting (IF) is a promising dietary intervention for T2D risk reduction, but its protective effect and mechanism on diabetic cognitive dysfunction remain elusive. Gut microbiota plays a vital role interphasing diet and host physiology and pathology and highly affected by the dietary composition and patterns. It has been reported that the microbiota homeostasis is essential for maintenance of gut health and for modulating cognitive function. We hypothesized that gut microbiota might play a pivotal role in mediating protective effects of IF on diabetes-induced cognitive decline. Methods After a 28-day IF regimen treatment, cognitive behavioral tests and brain insulin signaling were assessed on db/db mice. The microbiota-metabolites-brain axis alterations were detected by multiple-omics analysis (transciptomics, 16S rRNA sequencing and metabolomics). A intergrade multi-omics analysis was performed to analyze the correlation among gut microbiota, plasma metabolites, and hippocampal gene expression. Results Here we found that a 28-day Intermittent fasting (IF) regimen improved cognitive deficits in db/db mice via a microbiota-metabolites-brain axis assessed by behavioral tests and multiple-omics analysis: IF activated AMPK/PGC1α signaling, enhanced mitochondrial biogenesis in hippocampus and elevated genes enriched in hippocampal metabolic function. Moreover, IF re-structured gut microbiota and improved plasma microbial metabolites in relation to diabetes and cognitive function, e.g., serotonin, 3-Indolepropionic acid, and bile acids. Integration of multi-omics data demonstrated strong links between IF-related genes, gut microbiome and metabolites. Furthermore, removal of gut microbiota with antibiotics partly abolished the observed benefits of IF on cognition and hippocampal metabolic function. Conclusions Taken together, the present study suggests a critical role of gut microbiota in connecting peripheral metabolism with brain function, which could lead to novel interventions against metabolism-implicated neurodegenerative pathophysiologies. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China.

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Intermittent Fasting Improves Lipid Metabolism Through Changes in Gut Microbiota in Diet-Induced Obese Mice

Medical Science Monitor ◽

10.12659/msm.926789 ◽

2020 ◽

Vol 26 ◽

Author(s):

Ya Deng ◽

Wanjun Liu ◽

Jianqing Wang ◽

Jun Yu ◽

Li-qi Yang

Keyword(s):

Lipid Metabolism ◽

Gut Microbiota ◽

Intermittent Fasting ◽

Obese Mice

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Abstract P241: Intermittent Fasting Lowers Blood Pressure In A Rat Model Of Hypertension By Modulating The Gut Microbiota

Hypertension ◽

10.1161/hyp.76.suppl_1.p241 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Huanan Shi ◽

Taylor Abo-Hamzy ◽

Robert M Bryan ◽

David J Durgan

Keyword(s):

Blood Pressure ◽

Gut Microbiota ◽

Intermittent Fasting ◽

Microbial Metabolites ◽

Targeted Metabolomics ◽

Oral Gavage ◽

Spontaneously Hypertensive ◽

Germ Free ◽

Wistar Kyoto ◽

Principle Coordinate Analysis

Studies have demonstrated that disruption of the gut microbiota, termed gut dysbiosis, plays a causal role in the development of hypertension (HT) in animal models and patients. Recent studies revealed that intermittent fasting alters the gut microbiota and the production of microbial metabolites. Thus, we hypothesized that every-other-day-fasting (EODF) would prevent elevations of blood pressure (BP) in spontaneously hypertensive stroke prone rat (SHRSP) by maintaining a healthy gut microbiota. Five-week old SHRSP rats and normotensive Wistar Kyoto (WKY) rats were randomized to be fed ad lib or on EODF for 10 weeks. BP was measured weekly, and cecal content and plasma were collected at the end of the study. To examine the roles of gut microbiota and microbial metabolites in hypertension, we performed whole-genome shotgun sequencing on cecal samples and non-targeted metabolomics on cecal contents and plasma. To examine the direct effects of the EODF altered microbiota on BP regulation and eliminate the confounding variable of fasting, pooled cecal contents of SHRSP and WKY animals fed ad lib or EODF were given to germ free (GF) rats by oral gavage. We found that ten-weeks EODF was able to prevent elevations of systolic BP (SBP) in SHRSP compared to ad lib fed SHRSP (~220 vs. ~170mmHg; n=6-8, p<0.05), and that germ free rats transplanted with SHRSP ad lib microbiota had a significantly higher SBP as compared to those transplanted with SHRSP EODF microbiota (~152 vs. ~140 mmHg; n=6-7, p<0.01), indicating that microbiota and their metabolites are accountable for the effects of EODF. Principle coordinate analysis showed that EODF significantly altered the overall composition of both WKY and SHRSP microbiota (WKY p<0.01, SHRSP p<0.009). Multi-omics analysis indicates distinct microbiome and metabolome in SHRSP compared to WKY, and significant alterations to each induced by EODF. These findings suggest that EODF is able to prevent hypertension in SHRSP, and this involves altering the gut microbiota and metabolome.

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Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Nature Communications ◽

10.1038/s41467-020-14676-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 16

Author(s):

Zhigang Liu ◽

Xiaoshuang Dai ◽

Hongbo Zhang ◽

Renjie Shi ◽

Yan Hui ◽

...

Keyword(s):

Cognitive Impairment ◽

Gut Microbiota ◽

Intermittent Fasting

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The beneficial effects of intermittent fasting: an update on mechanism, and the role of circadian rhythm and gut microbiota

HepatoBiliary Surgery and Nutrition ◽

10.21037/hbsn-20-317 ◽

2020 ◽

Vol 9 (5) ◽

pp. 597-602

Author(s):

Dandan Hu ◽

Zhibo Xie ◽

Yuqian Ye ◽

Suhad Bahijri ◽

Minshan Chen

Keyword(s):

Circadian Rhythm ◽

Gut Microbiota ◽

Intermittent Fasting ◽

Beneficial Effects

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Intermittent fasting - a potential approach to modulate the gut microbiota in humans? A systematic review

Nutrition and Healthy Aging ◽

10.3233/nha-200098 ◽

2021 ◽

pp. 1-8

Author(s):

Kate Llewellyn-Waters ◽

Mohammad M. Abdullah

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Gut Microbiota ◽

Dietary Habits ◽

Intermittent Fasting ◽

Gut Health ◽

Medline Search ◽

Beneficial Effects ◽

The Rich ◽

The Impact

Research on gut microbiota has increased in popularity over the past decade, with evidence associating different dietary habits with changes in the makeup of the rich ecosystem of microorganisms that performs a variety of functions and induces a range of health effects, within and well beyond the gastrointestinal tract. Similarly, intermittent fasting (IF), an umbrella term describing various regimens of periods of voluntary abstinence from food and drink, has classically been associated with favourable impacts on cardiovascular risk factors, body weight, circadian biology, and, more recently, the gut health..The objective of this PRISMA systematic review was to summarize the peer-reviewed literature of clinical trials related to the impact of IF regimens on the gut microbiota. A MEDLINE search was conducted using PubMed and the keywords “intermittent fasting”, “gut microbiota”, “microbes”, and others. Whilst the field is still in its infancy, an emerging body of evidence suggests beneficial effects of IF on the health of the gut through increasing the microbial diversity and abundance, with possible clinical implications related to improving the immune function and ameliorating the metabolic status. Further research in larger clinical trials is warranted before practical recommendations for the public health can be made.

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Intermittent Fasting Reshapes the Gut Microbiota and Metabolome and Reduces Weight Gain More Effectively Than Melatonin in Mice

Frontiers in Nutrition ◽

10.3389/fnut.2021.784681 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jingliang Liu ◽

Yifan Zhong ◽

Xin M. Luo ◽

Yanfei Ma ◽

Jianxin Liu ◽

...

Keyword(s):

Weight Gain ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Serum Glucose ◽

Potential Interaction ◽

Intermittent Fasting ◽

Adipocyte Size ◽

Metabolome Analysis ◽

Serum Parameters ◽

Fat Liver

Background: Intermittent fasting (IF) can reduce energy intake and body weight (BW). Melatonin has many known functions, which include reducing appetite and preventing excessive weight gain.Objective: This study aimed to investigate the effects of IF on body fat and the gut microbiota and metabolome as well as a potential interaction with melatonin.Methods: Male C57BL/6J mice (23.0 ± 0.9 g, 6 wk old) were randomly assigned into four groups (12 mice/group): control (C), intermittent fasting (F), melatonin (M), and intermittent fasting plus melatonin (MF). The C and M groups mice were provided with ad libitum access to food and water, while the F and MF groups underwent alternative-day feed deprivation (15 cycles total). Melatonin was administered in the drinking water of the M and MF groups. Blood, epididymal fat, liver tissue, and intestinal tissue and contents were collected for lab measurements, histology, and microbiota and metabolome analysis. Main effects and interactions were tested by 2-factor ANOVA.Results: IF significantly reduced BW gain and serum glucose, total cholesterol (TC) and triglyceride (TG) levels. Adipocyte size significantly decreased with IF, then the number of adipocytes per square millimeter significantly increased (P < 0.05). Compared to the C group, the M and MF groups had significantly higher serum melatonin levels (17 and 21%, respectively), although melatonin monotherapy had no effect on serum parameters and adipocytes. There was no interaction between IF and melatonin on BW gain and serum parameters except for on adipocyte area and number per square millimeter, Bacteroidetes and Akkermansia bacterial abundance, and the levels of the intestinal metabolites alanine, valine and isoleucine. IF changed the intestinal microbiota structure, with the F and MF groups clearly separating from the C and M groups. Metabolomic analysis showed that there was obvious separation between all four groups.Conclusions: IF, but neither melatonin nor the interaction between IF and melatonin, could alter intestinal microbiota and metabolism and prevent obesity by reducing BW gain, serum glucose, TC, and TG, and adipocyte size in mice.

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Restructuring the Gut Microbiota by Intermittent Fasting Lowers Blood Pressure

Circulation Research ◽

10.1161/circresaha.120.318155 ◽

2021 ◽

Author(s):

Huanan Shi ◽

Bojun Zhang ◽

Taylor Abo-Hamzy ◽

James W Nelson ◽

Chandra Shekar R Ambati ◽

...

Keyword(s):

Blood Pressure ◽

Gut Microbiota ◽

Intermittent Fasting ◽

Spontaneously Hypertensive ◽

Beneficial Effects ◽

Gut Dysbiosis ◽

Hypertension Prevention ◽

Plasma Metabolome ◽

Genome Shotgun Sequence ◽

G Protein Coupled

Raionale: : In recent years, it has been demonstrated that a pathological change in the gut microbiota, termed gut dysbiosis, can be an underlying factor for the development of hypertension. Prevention of this dysbiosis can attenuate or abolish hypertension. Translational mechanisms to prevent gut dysbiosis as well as understanding of the mechanisms linking gut dysbiosis to hypertension are lacking. Objective: We first examined the efficacy of intermittent fasting (IF) in altering the gut microbiota and lowering blood pressure (BP). Next, we utilized a multi-omics approach to examine microbial influenced metabolites that may serve as the link between the gut microbiota and host BP regulation. Methods and Results: We demonstrate that IF significantly altered the makeup of the gut microbiota, cecal and plasma metabolome, and prevented the development of hypertension in the spontaneously hypertensive stroke-prone rat (SHRSP). The beneficial effects of IF were shown to be due to alterations of the gut microbiota through germ-free (GF) transplantation studies. GF rats receiving microbiota from IF SHRSP had significantly lower BP as compared to GF rats receiving microbiota from ad libitum fed SHRSPs. Through whole genome shotgun sequence analysis of the microbiota and untargeted metabolomics of cecal content and plasma we identified bile acid (BA) metabolism as a potential mediator in BP regulation. Finally, we show supplementation with cholic acid, or activation of the G protein-coupled BA receptor (TGR5), significantly reduced BP of the SHRSP. Conclusions: These studies demonstrate the BP lowering effects of IF involves manipulation of the gut microbiota and metabolome, and implicates disrupted BA signaling as novel mechanisms by which gut dysbiosis contributes to hypertension.

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Intermittent fasting and gut microbiota

The Turkish Journal of Gastroenterology ◽

10.5152/tjg.2019.101219 ◽

2020 ◽

Vol 30 (12) ◽

pp. 1008-1008

Author(s):

Tarkan Karakan ◽

Keyword(s):

Gut Microbiota ◽

Intermittent Fasting

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