Diet and the microbiota - gut - brain-axis: a primer for clinical nutrition

Abstract

Purpose of review: Diet is an essential modulator of the microbiota - gut - brain communication in health and disease. Consequently, diet-induced microbiome states can impact brain health and behaviour. The integration of microbiome into clinical nutrition perspectives of brain health is sparse. This review will thus focus on emerging evidence of microbiome-targeted dietary approaches with the potential to improve brain disorders.

Recent findings: Research in this field is evolving toward randomized controlled trials using dietary interventions with the potential to modulate pathways of the microbiota - gut - brain-axis. Although most studies included small cohorts, the beneficial effects of Mediterranean-like diets on symptoms of depression or fermented foods on the immune function of healthy individuals shed light on how this research line can grow. With a clinical nutrition lens, we highlight several methodological limitations and knowledge gaps, including the quality of dietary intake information, the design of dietary interventions, and missing behavioural outcomes.

Summary: Findings in diet - microbiome - brain studies can have groundbreaking implications in clinical nutrition practice and research. Modulating brain processes through diet via the gut microbiota raises numerous possibilities. Novel dietary interventions targeting the microbiota - gut - brain-axis can offer various options to prevent and treat health problems such as mental disorders. Furthermore, knowledge in this field will improve current nutritional guidelines for disease prevention.

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FIGURE 1

Interactions between diet and microbiota–gut–brain-axis mechanisms. A healthy diet comprising foods with complex food matrices, varied sources of dietary fibre, phytochemicals, or live bacteria (green box, 1) results in the growth of beneficial bacteria, production of neuroactive molecules and other health-promoting metabolites such as short-chain fatty acids (SCFA), 2. SCFA can act on enteroendocrine L cells secreting the anorexigenic peptides glucagon-like peptide-1 (GLP-1) and peptide Y.Y. (PYY), acting on hypothalamic centres for homeostatic control of feeding behaviour (3). SCFAs also contribute to the host intestinal barrier integrity and immunity, regulating the suppression of cytokine production from myeloid cells and differentiating T regulatory and T helper cell differentiation (4). In addition, gut bacteria can stimulate the conversion of neurotransmitter precursors into active forms, such as the dietary tryptophan (Trp) into 5-hydroxytryptamine (5-HT) by Enterochromaffin cells (5). Other bacteria can produce active neurotransmitters such as norepinephrine and dopamine that can interact with the enteric nervous system or stimulate vagal sensory neurons (e.g., neuropod) in the gut (6), leading to activation in the brain structures, controlling homeostatic and reward-related feeding behaviour (7). Contrary, a western-like dietary pattern comprising processed foods lacking dietary fibre and with higher content of saturated fat, salt, and food additives (red box, 8) can lead to decreased gut microbiome's diversity, altered bile acids metabolism, lower abundance of mucus-stimulating microorganisms and consequently, compromised gut-barrier integrity, including loosening of tight-junctions (9). In addition, the release of intestinal inflammation markers and translocation of endotoxins from the gut lumen to the bloodstream can induce a low-grade systemic inflammation (10) that has been associated with mental illness and impaired metabolic regulation.