Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders

Abstract

There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health, and for several brain disorders. The BGM system is made up of neuroendocrine, neural, and immune communication channels which establish a network of bidirectional interactions between the brain, the gut and its microbiome. Diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels. In this review, we summarize the evidence available from preclinical and clinical studies on the influence of dietary habits and interventions on a selected group of psychiatric and neurologic disorders including depression, cognitive decline, Parkinson's disease, autism spectrum disorder and epilepsy. We will particularly address the role of diet-induced microbiome changes which have been implicated in these effects, and some of which are shared between different brain disorders. While the majority of these findings have been demonstrated in preclinical and in cross-sectional, epidemiological studies, to date there is insufficient evidence from mechanistic human studies to make conclusions about causality between a specific diet and microbially mediated brain function. Many of the dietary benefits on microbiome and brain health have been attributed to anti-inflammatory effects mediated by the microbial metabolites of dietary fiber and polyphenols. The new attention given to dietary factors in brain disorders has the potential to improve treatment outcomes with currently available pharmacological and non-pharmacological therapies.

Fig. 1. The influence of food on the brain gut microbiome system.

The brain connectome, gut connectome and microbiome make up the 3 hubs in the larger BGM network. All hubs are linked by bidirectional connections with multiple feedback loops generating a non-linear system. Different components of food influence the brain, the gut and the gut microbiome via different communication channels. Dietary components can influence the gut directly and reach the brain after absorption in the small intestine. In addition, diet can influence gut microbial composition and diversity, and after microbial metabolism can modulate the gut connectome. Some of the microbial derived molecules are absorbed and reach the brain via the systemic circulation and/or the vagus nerve (see Fig. 2) Similarly, the brain can modulate the microbiome directly through the effect of neuroactive substances released into the gut lumen affecting gene expression and behavior of microbes, or indirectly via alterations of the gut microbial environment. Modified with permission from Martin et al., 2018.

Fig. 2. Gut microbes generate neuroactive metabolites from tryptophan.

The essential amino acid Tryptophan is the precursor for a number of neuroactive signaling molecules including serotonin, kynurenine and indoles. Whereas microbes only play a modulatory role in the generation of serotonin and kynurenine, the synthesis of indoles is fully dependent on gut microbial metabolism. The relative abundance of the 3 metabolites is dependent on tryptophan intake, on the relative abundance of involved microbial taxa and on stress induced input from the autonomic nervous system. Modified with permission from Martin et al., 2018.

Fig. 3. Four sources for gut microbial signaling molecules.

Gut microbial signaling molecules are derived from at least 4 different sources: Diet-derived, microbe-derived, host-derived and newly synthesized molecules. Chemical transformation of these molecules results in a vast number of signaling molecules which can influence not only cells in the gut (immune, nerve, endocrine cells), but following dissemination throughout the body are able to modulate all organs, including the brain. Certain diet-derived microbial metabolites have neuroactive effects on the central and autonomic nervous system, while microbial cell wall components can activate the immune system by interacting with TLRs. Some microbial metabolites (in particular the SCFA butyrate) exert anti-inflammatory effects. Modified with permission from Needham et al., 2020.