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Brain–gut–microbiome interactions in obesity and food addiction

Nature Reviews Gastroenterology & Hepatology volume 17, pages 655–672 (2020)Cite this article

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Abstract

Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain–gut–microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis.

Key points

  • Food addiction refers to maladaptive ingestive behaviours resulting from a shift from primarily homeostatic to hedonic regulatory mechanisms of food intake; this shift reflects alterations at all levels of the brain–gut–microbiome (BGM) axis.

  • Normal ingestive behaviour is the result of the tightly regulated interplay between orexigenic and anorexigenic gut hormones, leptin signalling from adipose tissue, hypothalamic nuclei, the dopaminergic reward system and prefrontal inhibitory influences.

  • In food addiction, a disinhibition of reward and anorexigenic mechanisms at all levels of the BGM axis results in unrestrained craving for food.

  • Several adverse early-life events, including nutrition, stress and antibiotic intake, can influence the development of BGM interactions and of ingestive behaviour.

  • Lifelong dietary choices can modulate BGM interactions and eating behaviours; for example, chronic ingestion of a Western diet can result in systemic low-grade immune system activation, reducing feedback inhibitory mechanisms restraining food intake.

  • Pharmacological treatment options for food addition are limited and bariatric surgery is the only therapy providing long-term benefits; however, novel treatment approaches, including time-restricted eating and cognitive behavioural interventions, are being evaluated.

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Fig. 1: Model of brain–gut–microbiome interactions in ingestive behaviour.
Fig. 2: Model of altered brain network interactions in food addiction.
Fig. 3: Mechanisms in the homeostatic and hedonic systems leading to food addiction.
Fig. 4: Interactions between food, gut microbiota and intestinal permeability in the regulation of ingestive behaviour.
Fig. 5: Circular model of brain–gut–microbiome interactions in obesity and targets for intervention.

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Acknowledgements

We acknowledge C. P. Sanmiguel for her contributions in making editorial suggestions to the gut-directed therapies section of this review and C. Liu for invaluable editorial services. E.A.M. has been supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK048351, DK064539 and DK096606). A.G. has been supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK106528) and CURE at the University of California, Los Angeles/Clinical and Translational Science Institute (ULTR001881/DK041301).

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Authors and Affiliations

  1. G. Oppenheimer Family Center for Neurobiology of Stress and Resilience, Ingestive Behavior and Obesity Program, University of California Los Angeles, Los Angeles, CA, USA

    Arpana Gupta, Vadim Osadchiy & Emeran A. Mayer

  2. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Arpana Gupta, Vadim Osadchiy & Emeran A. Mayer

  3. Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA, USA

    Arpana Gupta & Emeran A. Mayer

  4. Ahmanson-Lovelace Brain Mapping Center at University of California Los Angeles, University of California Los Angeles, Los Angeles, CA, USA

    Emeran A. Mayer

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Correspondence to Emeran A. Mayer.

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

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Nature Reviews Gastroenterology & Hepatology thanks R. Brown, E. Jerlhag, P. Kenny and L. Leggio for their contribution to the peer review of this work.

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Glossary

Systems biology

An interdisciplinary field of study that focuses on complex interactions within multiple biological systems, rather than focusing on individual mechanisms.

Hedonic-driven eating behaviour

The continued consumption of highly palatable foods even after energy requirements have been met (also known as ‘food addiction’).

Dopaminergic reward system

The extensive network of neurons in the extended reward network that depend on dopamine as the primary neurotransmitter for reward-related processing.

Extended reward network

A network comprising interconnecting brain networks such as reward and salience networks, associated with processing of reward stimuli and modulation of food-seeking behaviours (used interchangeably with ‘greater reward system’).

Neural substrates

A brain region or network associated with a specific behaviour.

Cortical performance monitoring

Processes associated with reward sensitivity, motivation, interoceptive awareness, stress reactivity and self-control.

Nucleus accumbens

Region of the basal ganglia and a key hub for the core reward system, responsible for many dopaminergic processes, especially those related to pleasure, motivation and aversion.

Ventral tegmental area

Key region of the midbrain that houses the dopaminergic cell bodies that project to all regions of the core and extended reward network.

Salience network

The brain network responsible for monitoring the homeostatic state of the body to make adaptive adjustments to real or expected disturbances in homeostasis through the autonomic nervous system and behavioural responses.

Corticostriatal communication

The extensive communication network between the cortex, which houses the extended reward network (including the frontal cortex and insula) and the striatum, which houses the core reward network (nucleus accumbens, basal ganglia).

Prebiotic

Dietary fibre or other substrates that can only be digested by commensal gut microorganisms, thereby promoting gut microbiota diversity and health.

Maladaptive coping

Behaviours used to cope with stressful situations to alleviate the stress or symptoms, but are not necessarily healthy and do not address the core cause of the stress.

Psychosocial stress

Stress originating from the environment that is sufficient to cause dysregulation of homeostatic responses and physical or psychological symptoms.

Perceived stress

Stress from events in an individual’s life perceived as stressful. The most widely used scale for perceived stress is the Perceived Stress Scale.

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Gupta, A., Osadchiy, V. & Mayer, E.A. Brain–gut–microbiome interactions in obesity and food addiction. Nat Rev Gastroenterol Hepatol 17, 655–672 (2020). https://doi.org/10.1038/s41575-020-0341-5

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