Effect of a vegetarian diet on the gut microbiome and major depressive disorder

Abstract

Major depressive disorder (MDD) is one of the leading contributors to global disease burden. There are several mechanisms that might affect MDD. First of all, several neurotransmitters are involved in MDD; reduced levels of serotonin, dopamine noradrenaline, norepinephrine, epinephrine and GABA are associated with MDD. Contrarily, excessive levels of glutamate can aggravate depressive symptoms. Besides neurotransmitters, levels of brain-derived neurotrophic factor (BDNF) are reduced in MDD patients. Furthermore, MDD is characterized by a hyperactive hypothalamic-pituitary-adrenal (HPA) axis. Lastly, inflammation seems to aggravate depressive symptoms. The gut-brain axis has been demonstrated to be involved in the pathogenesis of depression. First of all, gut microbes can regulate the synthesis of neurotransmitters, which can signal the vagus nerve or enter the blood circulatory system. Furthermore, the gut can produce metabolites that affect the brain, most prominently short-chain fatty acids (SCFAs). Lastly, gut microbes can have (anti-)inflammatory effects on the host. Although gut microbes can affect the brain via the gut-brain axis, there is no clear shift in the microbiome composition of MDD patients, as literature reports are conflicting. Nonetheless, probiotic studies indicate that Lactobacillus and Bifidobacterium can alleviate depressive symptoms. A vegetarian diet decreased Bifidobacterium species and Lactobacillus amylovorus, suggesting a disadvantageous effect of a vegetarian diet on MDD. Meat consumption enhances serotonin and tryptophan (serotonin precursor) levels in the gut. However, this does not necessarily enhance serotonergic neurotransmission in the brain. Besides serotonin, tryptophan is also a precursor for kynurenine. Kynurenine can induce a neurotoxic effect. Meat consumption may inhibit kynurenine pathway by increasing Lactobacillus. However, meat-induced inflammation may upregulate the neurotoxic pathway of kynurenine. Besides tryptophan, tyrosine might also affect MDD. Tyrosine is a precursor for dopamine, epinephrine and norepinephrine. Tyrosine is synthesized in the gut. However, dietary tyrosine did not induce antidepressant effects. Thus, the effect of tyrosine metabolism on MDD remains unclear. Vitamins might affect MDD as well. Both vitamins abundant in a vegetarian diet (folate) as well as in an omnivorous diet (B12) could enhance monoaminergic neurotransmission. Moreover, meat, which is high in sulfide and zinc, seems to stimulate GABAergic neurotransmission and inhibit glutamergic neurotransmission. D-amino acids, which are abundant in a vegetarian diet, may stimulate glutamatergic neurotransmission, whilst folate seems to reduce it. Moreover, both a vegetarian and omnivorous diet can result in metabolites that enhance BDNF levels. Lastly, it is important to emphasize that an omnivorous diet induces inflammation, which could aggravate MDD. Hence, through different metabolites, a vegetarian and omnivorous diet are able to either positively or negatively impact MDD. The conflicting results might suggest there is no direct relation between a vegetarian diet and MDD. Nonetheless, ambiguous results might also suggest the need for additional research, as the relation between diet, the gut microbiome and cognitive functioning is very complex.