Beneficial gut microbiome remodeled during intermittent fasting in humans

The obesity epidemic and its metabolic consequences are a major public health problem both in the USA and globally. While the underlying causes are multifactorial, dysregulations within the brain–gut–microbiome (BGM) system play a central role. Normal eating behavior is coordinated by the tightly regulated balance between intestinal, extraintestinal and central homeostatic and hedonic mechanisms, resulting in stable body weight. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food has played a crucial role in shifting this balance towards hedonic eating through both central (disruptions in dopaminergic signaling) and intestinal (vagal afferent function, metabolic toxemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. The balance between homeostatic and hedonic eating behaviors is not only influenced by the amount and composition of the diet, but also by the timing and rhythmicity of food ingestion. Circadian rhythmicity affects both eating behavior and multiple gut functions, as well as the composition and interactions of the microbiome with the gut. Profound preclinical effects of intermittent fasting and time restricted eating on the gut microbiome and on host metabolism, mostly demonstrated in animal models and in a limited number of controlled human trials, have been reported. In this Review, we will discuss the effects of time-restricted eating on the BGM and review the promising effects of this eating pattern in obesity treatment.

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Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival indb/dbMice

Diabetes ◽

10.2337/db18-0158 ◽

2018 ◽

Vol 67 (9) ◽

pp. 1867-1879 ◽

Cited By ~ 61

Author(s):

Eleni Beli ◽

Yuanqing Yan ◽

Leni Moldovan ◽

Cristiano P. Vieira ◽

Ruli Gao ◽

...

Keyword(s):

Gut Microbiome ◽

Intermittent Fasting

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Effect of time restricted feeding on the gut microbiome in adults with obesity: A pilot study

Nutrition and Health ◽

10.1177/0260106020910907 ◽

2020 ◽

Vol 26 (2) ◽

pp. 79-85 ◽

Cited By ~ 3

Author(s):

Kelsey Gabel ◽

Jarrad Marcell ◽

Kate Cares ◽

Faiza Kalam ◽

Sofia Cienfuegos ◽

...

Keyword(s):

Gut Microbiome ◽

Phylogenetic Diversity ◽

Gene Sequencing ◽

Fecal Microbiota ◽

Intermittent Fasting ◽

Restricted Feeding ◽

Total Abundance ◽

Ribosomal Ribonucleic Acid ◽

Stool Samples ◽

16 S Rrna

Background: Time restricted feeding is a form of intermittent fasting where participants shorten the daily window in which they eat. Aim: This is the first study to examine the effects of intermittent fasting on changes in the gut microbiome. Methods: Adults with obesity ( n = 14) participated in a daily 8-hour time restricted feeding intervention (8-hour feeding window/16-hour fasting window) for 12 weeks. Fecal microbiota were determined by 16 S rRNA (ribosomal ribonucleic acid) gene sequencing of stool samples. Results: Body weight decreased ( P < 0.05) by -2 ± 1 kg. Gut microbiota phylogenetic diversity remained unchanged. The two most common phyla were Firmicutes and Bacteroidetes accounting for 61.2% and 26.9% of total abundance at baseline. No significant alterations in the abundance of Firmicutes, Bacteroidetes, or any other phyla were detected after 12 weeks of time restricted feeding. Conclusions: Time restricted feeding did not significantly alter the diversity or overall composition of the gut microbiome.

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Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension

Journal of the American Heart Association ◽

10.1161/jaha.121.022722 ◽

2021 ◽

Author(s):

Sasha Z. Prisco ◽

Megan Eklund ◽

Daphne M. Moutsoglou ◽

Anthony R. Prisco ◽

Alexander Khoruts ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Right Ventricular ◽

Gut Microbiome ◽

Cardiomyocyte Hypertrophy ◽

Intermittent Fasting ◽

Sprague Dawley ◽

Pulmonary Arterial ◽

Ad Libitum ◽

Rv Function

Background Intermittent fasting (IF) confers pleiotropic cardiovascular benefits including restructuring of the gut microbiome and augmentation of cellular metabolism. Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by right ventricular (RV) mitochondrial dysfunction and resultant lipotoxicity and microbiome dysbiosis. However, the effects of IF on RV function in PAH are unexplored. Therefore, we investigated how IF altered gut microbiota composition, RV function, and survival in the monocrotaline model of PAH. Methods and Results Male Sprague Dawley rats were randomly allocated into 3 groups: control, monocrotaline‐ad libitum feeding, and monocrotaline‐IF (every other day feeding). Echocardiography and invasive hemodynamics showed IF improved RV systolic and diastolic function despite no significant change in PAH severity. IF prevented premature mortality (30% mortality rate in monocrotaline‐ad libitum versus 0% in monocrotaline‐IF rats, P =0.04). IF decreased RV cardiomyocyte hypertrophy and reduced RV fibrosis. IF prevented RV lipid accrual on Oil Red O staining and ceramide accumulation as determined by metabolomics. IF mitigated the reduction in jejunum villi length and goblet cell abundance when compared with monocrotaline‐ad libitum. The 16S ribosomal RNA gene sequencing demonstrated IF changed the gut microbiome. In particular, there was increased abundance of Lactobacillus in monocrotaline‐IF rats. Metabolomics profiling revealed IF decreased RV levels of microbiome metabolites including bile acids, aromatic amino acid metabolites, and gamma‐glutamylated amino acids. Conclusions IF directly enhanced RV function and restructured the gut microbiome. These results suggest IF may be a non‐pharmacological approach to combat RV dysfunction, a currently untreatable and lethal consequence of PAH.

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Intermittent fasting contributes to aligned circadian rhythms through interactions with the gut microbiome

Beneficial Microbes ◽

10.3920/bm2020.0149 ◽

2021 ◽

pp. 1-16

Author(s):

M.C. Daas ◽

N.M. de Roos

Keyword(s):

Circadian Rhythms ◽

Gut Microbiome ◽

Short Chain Fatty Acids ◽

Intermittent Fasting ◽

Bacterial Populations ◽

Signalling Molecules ◽

Treatment And Prevention ◽

Wide Range ◽

Dietary Strategy ◽

The Impact

The timing of food consumption is considered to be an important modulator of circadian rhythms, regulating a wide range of physiological processes which are vital to human health. The exact mechanisms underlying this relationship are not fully understood, but likely involve alterations in the structure and functioning of the gut microbiome. Therefore, this narrative review aims to clarify these mechanisms by focusing on intermittent fasting as a dietary strategy of food timing. A literature search identified 4 clinical and 18 preclinical studies that examined either (1) the impact of intermittent fasting on the gut microbiome, or (2) whether circadian rhythms of the host are subject to changes in the bacterial populations in the gut. Results reveal that intermittent fasting directly influences the gut microbiome by amplifying diurnal fluctuations in bacterial abundance and metabolic activity. This in turn leads to fluctuations in the levels of microbial components (lipopolysaccharide) and metabolites (short-chain fatty acids, bile acids, and tryptophan derivates) that act as signalling molecules to the peripheral and central clocks of the host. Binding of these substrates to pattern-recognition receptors on the surface of intestinal epithelial cells in an oscillating manner leads to fluctuations in the expression of circadian genes and their transcription factors involved in various metabolic processes. Intermittent fasting thus contributes to circadian rhythmicity in the host and could hold promising implications for the treatment and prevention of diseases associated with disordered circadian rhythms, such as obesity and metabolic syndrome. Future intervention studies are needed to find more evidence on this relationship in humans, as well as to clarify the optimal fasting regimen for balanced circadian rhythms.

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Recent advances and health implications of dietary fasting regimes on the gut microbiome

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00475.2020 ◽

2021 ◽

Author(s):

Alex E Mohr ◽

Eric Gumpricht ◽

Dorothy D Sears ◽

Karen L. Sweazea

Keyword(s):

Calorie Restriction ◽

Gut Microbiome ◽

Dietary Intervention ◽

Health Impact ◽

Intermittent Fasting ◽

Clinical Effects ◽

Ongoing Research ◽

Clinical Benefits ◽

Methodological Considerations ◽

The Impact

Calorie restriction is a primary dietary intervention demonstrated over many decades in cellular and animal models to modulate aging pathways, positively affect age-associated diseases, and, in clinical studies, to promote beneficial health outcomes. Because long-term compliance with daily calorie restriction has proven problematic in humans several intermittent fasting (IF) regimens, including alternate day fasting (ADF) and time-restricted feeding (TRF), have evolved revealing similar clinical benefits as calorie restriction. Despite significant research on the cellular and physiological mechanisms contributing to, and responsible for, these observed benefits, relatively little research has investigated the impact of these various fasting protocols on the gut microbiome (GM). Reduced external nutrient supply to the gut may beneficially alter the composition and function of a 'fed' gut microflora. Indeed, the prevalent, obesogenic Western diet can promote deleterious changes in the GM, signaling intermediates involved in lipid and glucose metabolism, and immune responses in the gastrointestinal tract. This review describes recent preclinical and clinical effects of varying fasting regimens on GM composition and associated physiology. Although the number of preclinical and clinical interventions are limited, significant data thus far suggest fasting interventions impact GM composition and physiology. However, there are considerable heterogeneities of study design, methodological considerations, and practical implications. Ongoing research on the health impact of fasting regimes on GM modulation is warranted.

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Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000624 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sunmin Park ◽

Sunna Kang ◽

Da Sol Kim

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Insulin Signaling ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Memory Function ◽

Amyloid Β ◽

Impaired Memory ◽

Ca1 Region ◽

Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

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