Antibiotics and mental health: The good, the bad and the ugly

Abstract

Antibiotics are recognised as, on occasion, producing psychiatric side effects, most notably depression and anxiety. Apart from antimicrobial activity, antibiotics have multiple off-target effects. The brain-gut-microbiota axis has multiple sites for off-target activity, which may produce either positive or negative antibiotic effects. Here we review how antibiotics impact mental health by acting through the brain-gut-microbiota axis. Microbes in the gut influence brain function by acting through the vagus nerve or by altering the production of short-chain fatty acids or the amino acid tryptophan, the building block of serotonin. Not all antimicrobial actions of antibiotics have a negative impact. The first antidepressant discovered was actually an antibiotic: isoniazid is an antibacterial drug developed for treating tuberculo-sis. Minocycline, which enters the brain and mediates its effects through microglia, shows antidepressant activity. Some antibiotics bring about a significant decrease in gut microbial diversity, and this is viewed as a risk factor for depression. Other risk factors induced by antibiotics include altered gut barrier function, activation of the hypothalamic-pituitary-adrenal axis, reducing levels of brain-derived neurotrophic factor or oxytocin and alteration of vagal tone. Although most patients taking antibiotics do not suffer from an iatrogenic psychiatric disorder, some do. As clinicians, we need to keep this in mind. The development of new antibiotics is primarily focused on antibiotic resistance, but efforts should be made to reduce off-target braingut-microbiota effects resulting in mental health problems.

Prophylactic Effect of Bovine Colostrum on Intestinal Microbiota and Behavior in Wild-Type and Zonulin Transgenic Mice

“…Research shows that diet can both modulate the intestinal microbiota for maintaining or boosting/building eubiosis, or in the direction of developing dysbiosis [67][68][69][70][71][72][73][74][75][76][77]. Currently, the best-studied environmental effectors in microbiome variation are diet and antibiotic treatment [67,73,[78][79][80][81][82][83][84][85]. However, understanding intestinal microbiota active modulation through external exposome and its impact on behavior or disease propensity is still in its infancy [15].…”

Constitutively active microglial populations limit anorexia induced by the food contaminant deoxynivalenol

“…In our hands, minocycline pretreatment dramatically reduced CD68 expression within the DVC and hypothalamus and worsened DON-induced anorexia and neuronal activation, as we previously observed after microglia deletion by PLX3397. Minocycline, like most antibiotics, has off-targets such as modulation of iron chelation, oxidative stress or leucocyte functions [ 88 , 89 ], which nevertheless must be kept in mind as interference on the results obtained, even if unlikely. More broadly, even though we used two different pharmacological compounds, i.e., PLX3397 and minocycline, to limit possible non-specific effects, we cannot totally exclude that the modulation of peripheral tissues or cells, such as macrophages contributes, in addition to modulation of microglia activity in CVOs, to exacerbate response to DON.…”

Recent nanoengineered diagnostic and therapeutic advancements in management of Sepsis

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