Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 10;13(2):584.
doi: 10.3390/nu13020584.

Brain-Gut-Microbiome Interactions and Intermittent Fasting in Obesity

Juliette Frank  1 , Arpana Gupta  1 , Vadim Osadchiy  1 , Emeran A Mayer  1
Affiliations
Review

Brain-Gut-Microbiome Interactions and Intermittent Fasting in Obesity

Juliette Frank et al. Nutrients. .

Abstract

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.

Keywords: diurnal rhythm; food addiction; gut microbiome; ingestive behavior; weight loss.

PubMed Disclaimer

Conflict of interest statement

E.A.M. serves on the scientific advisory boards of Amare, Axial Therapeutics, Bloom Science, Danone, Viome, Pendulum, Mahana Therapeutics and APC Microbiome Ireland. J.F., A.G. and V.O. declare no competing interests.

Figures

Figure 1
Figure 1
Bidirectional interactions within the brain gut microbiome (BGM) system are modulated by diurnal oscillations. Outputs generated by the central autonomic brain network modulate the activity of various components of the gut connectome (immune, endocrine, epithelial cells, gap junctions, smooth muscle, neurons) which influence gut function and interactions of the gut with the microbiome. Sympathetic nervous system outflow from the brain can also modulate gut microbial gene expression and function directly. Both gut and brain induced modulation of gut microbial metabolites and secretion of neuroactive neuroactive and inflammatory signaling molecules feed back to the brain and modulate the activity of brain networks. Diurnal variations (depicted by an oscillating line), food intake, sleep and physical activity modulate autonomic nervous system (ANS) activity as well as gut microbial composition and function. Oscillations between the brain and the gut are synchronized with the central clock in the hypothalamic suprachiasmatic nucleus. Modified with permission from Osadchiy et al. [21] and Chaix et al. [22].
Figure 2
Figure 2
Reported benefits associated with time-restricted eating (TRE). Based largely on preclinical studies a wide range of benefits have been postulated for TRE, while clinical studies are non-conclusive to date. With permission from Chaix et al. [92].
See this image and copyright information in PMC

References

    1. CDC. Centers for Disease Control and Prevention Overweight and Obesity. [(accessed on 19 September 2020)]; Available online: http://www.cdc.gov/obesity/data/adult.html.
    1. Zhang Y., Liu J., Yao J., Ji G., Qian L., Wang J., Zhang G., Tian J., Nie Y., Zhang Y.E., et al. Obesity: Pathophysiology and intervention. Nutrients. 2014;6:5153–5183. doi: 10.3390/nu6115153. - DOI - PMC - PubMed
    1. Hatori M., Vollmers C., Zarrinpar A., DiTacchio L., Bushong E.A., Gill S., Leblanc M., Chaix A., Joens M., Fitzpatrick J.A., et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15:848–860. doi: 10.1016/j.cmet.2012.04.019. - DOI - PMC - PubMed
    1. Lowe D.A., Wu N., Rohdin-Bibby L., Moore A.H., Kelly N., Liu Y.E., Philip E., Vittinghoff E., Heymsfield S.B., Olgin J.E., et al. Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. JAMA Intern. Med. 2020;180:1491–1499. doi: 10.1001/jamainternmed.2020.4153. - DOI - PMC - PubMed
    1. Gupta A., Osadchiy V., Mayer E.A. Brain-gut-microbiome interactions in obesity and food addiction. Nat. Rev. Gastroenterol. Hepatol. 2020;17:655–672. doi: 10.1038/s41575-020-0341-5. - DOI - PMC - PubMed

LinkOut - more resources