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Review
. 2021 Jul 30;12(4):1239-1285.
doi: 10.1093/advances/nmaa181.

Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health

Kirsten Berding  1 , Klara Vlckova  1 , Wolfgang Marx  2 , Harriet Schellekens  1   3 , Catherine Stanton  1   4 , Gerard Clarke  1   5 , Felice Jacka  2   6   7   8 , Timothy G Dinan  1   5 , John F Cryan  1   3
Affiliations
Review

Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health

Kirsten Berding et al. Adv Nutr. .

Abstract

Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota-gut-brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss potential underlying mechanisms. Additionally, determinants of the responsiveness to a dietary intervention and evidence for the microbiota as an underlying modulator of the effect of diet on brain health are outlined. In particular, we emphasize the understudied use of whole-dietary approaches in this endeavor and the need for greater evidence from clinical populations. While promising results are reported, additional data, specifically from clinical cohorts, are required to provide evidence-based recommendations for the development of microbiota-targeted, whole-dietary strategies to improve brain and mental health.

Keywords: behavior; brain; diet; gut–brain axis; mechanisms; mental health; microbiota; nutrition.

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Figures

FIGURE 1
FIGURE 1
Diet and the microbiota–gut–brain axis at the extremes of life. Diet could influence the microbiota–gut–brain axis across the lifespan. During the prenatal period, maternal diet influences cognitive development of the offspring, potentially through some microbiota-mediated mechanisms. In infancy, breast or formula feeding majorly impact the microbiota composition. Emerging research is suggesting that this could affect brain and behavior. The timing of the “weaning response” could be important in driving the development of the microbiota–brain interaction. Continued development of the microbiota–gut–brain axis during childhood and adolescence could mark additional sensitive periods during which healthy dietary intake might be important for proper development of the axis. In elderly individuals the microbiota again undergoes changes, which could be driven partly by dietary intake. These changes in microbiota could be linked to frailty, “inflamm-aging” and cognitive function.
FIGURE 2
FIGURE 2
Mechanism of the gut–brain communication prone to dietary modulation. Multiple mechanisms exist whereby diet could modulate the gut-to-brain communication, including microbial-derived metabolites, hormonal, immune, metabolic, and neuronal pathways. Healthy dietary intake (e.g., dietary fiber, polyphenols, or fermented foods) can promote the growth of beneficial microbes. These microbes can stimulate production of bioactive metabolites, neurotransmitters [e.g., serotonin (5-HT)], and gut hormones, which can affect brain and behavior through direct or indirect signaling pathways. Another important avenue of communication is stimulation of the vagus nerve through microbial metabolites from food degradation or microbes. Unhealthy dietary habits (e.g., Western diets) can lead to the proliferation of harmful bacteria. This gut “dysbiosis” could result in dysfunctional brain processes and neuroinflammation through alterations in bile acid metabolism, intestinal permeability, inflammation, and metabolic pathways. BBB, blood–brain barrier; HPA, hypothalamic–pituitary–adrenal.
FIGURE 3
FIGURE 3
Mediating compared with moderating interactions between diet, microbiota, and the brain. Both a moderating and a mediating relation between diet, microbiota, and the brain could be proposed. (A) In the moderating relation, diet could strengthen or weaken the microbiota–brain interaction, whereas in a (B) mediating relation diet directly changes the microbiota composition and function to influence brain processes. The potential direct effect of the diet on brain processes is depicted by dashed lines.
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