Antibiotics May Trigger Mitochondrial Dysfunction Inducing Psychiatric Disorders

Abstract

Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes. Accordingly, perturbation of normative mitochondrial function by select classes of antibiotics is certainly reflective of the high degree of evolutionary pressure designed to maintain ongoing bidirectional signaling processes between cellular compartments. These issues are of critical importance in evaluating potentially severe side effects of antibiotics on complex behavioral functions mediated by CNS neuronal groups. The CNS is extremely dependent on delivery of molecular oxygen for maintaining a required level of metabolic activity, as reflected by the high concentration of neuronal mitochondria. Thus, it is not surprising to find several distinct behavioral abnormalities conforming to established psychiatric criteria that are associated with antibiotic usage in humans. The manifestation of acute and/or chronic psychiatric conditions following antibiotic usage may provide unique insights into key etiological factors of major psychiatric syndromes that involve rundown of cellular bioenergetics via mitochondrial dysfunction. Thus, a potential window of opportunity exists for development of novel therapeutic agents targeting diminished mitochondrial function as a factor in severe behavioral disorders.

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

“…Thus, almost all of the nonantibiotics mentioned above affect mitochondrial functions being either part of their modes of action or potential toxicities. Many antibiotics cause mitochondrial dysfunction, too, thus explaining their anti-neoplastic activities [30], or possibly promoting tumorigenesis [265][266][267][268], obesity [269], and psychiatric disorders [270,271]. Thus, antibiotics as well as non-antibiotics exert beneficial or detrimental antimitochondrial activities.…”

Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

“…Moreover, antibiotic-resistance was not always, but usually, associated with a significant economic burden resulting from (re-)admission to hospital, need for i.v.-administration, or even use of a less well tolerated antibiotic [390][391][392][393][394][395][396]. Antibiotics causing mitochondrial dysfunction may promote tumorigenesis [397][398][399][400], obesity [401], and psychiatric disorders [402,403]. Furthermore, this review has demonstrated that antibiotics may have an unpredictable impact on cell culture metabolism, gene expression and signalling cascades thus supporting a previous study entitled "are cell culture data skewed?"…”

The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling

“…These compounds were demonstrated to activate mitophagy by various mechanisms, including depletion of ATP or adenine nucleotide translocase-2 (ANT2) (Singh et al, 2009; Zhang C. et al, 2015). Interestingly, several antibiotics, including quinolones, aminoglycosides, and β-lactams, were found to damage mitochondria, inducing cellular senescence (Kalghatgi et al, 2013; Stefano et al, 2017). Conversely, tetracycline derivatives, doxycycline, and minocycline were associated with the activation of mitophagy in ECs, suggesting protective effects for biological barriers (Dong et al, 2015; Xing et al, 2017).…”