Mitochondria, Microbiome and Their Potential Psychiatric Modulation

Abstract

Pervasive developmental disorders, or autism spectrum disorders, are multifaceted and have a high rate of occurrence. Additionally, the origin of Autism appears to be multidimensional and largely unknown. Thus, it would appear novel approaches and concepts are needed in this area of scientific endeavor. In this regard, microbial cells harbored within the human gut and elsewhere are being studied to understand their multi-functional properties and their ability to affect physiological activities in their "host" organism. The communities of approximately 10 trillion microbial cells that live within the gut are involved in functions such as metabolism, nutrition and immune regulation. We and others surmise this microbiota can contribute to disruption of normal activities, causing harmful pathologies such as gastrointestinal complications, obesity, and diabetes and autism. They have the ability to trigger inappropriate immune activation, especially macrophages, which can travel from the gut and penetrate the blood brain barrier and communicate inappropriately with neural cells, altering behavior. Normally these immune cells can enter the brain and become microglia. However, being abnormally stimulated, many more can enter the brain, awakening the sentinel microglia and establishing a proinflammatory state, inducing hypoxia (altering mitochondrial performance). Thus, the microbiome has the potential to extend its influence into the brain, suggesting this may also take place within the parameters of normal activity. In part, the behavioral outcome of such an inappropriate invasion would depend on the region(s) penetrated, manifesting itself with a multidimensional behavioral profile such as occurs in autism.

Microbiota and Neurological Disorders: A Gut Feeling

“…147 Gut microbial dysregulation can alter one's immune status and cause aberrant social and cognitive behavior. 35 , 148 , 149 This may result in catastrophic consequences during long space flights, as for example, to Mars, if an astronaut's ability to carry out demanding tasks at a high performance and optimal level becomes severely compromised. 150 History shows that addressing the technological challenges space exploration presents has a constructive rippling effect on the technological advances made for a wide range of applications here on Earth.…”

Mitochondrial DNA heteroplasmy in human health and disease

“…The primacy of cancer as a mitochondrial metabolic disease has been proposed ( 31 – 33 ), in marked contrast to widely espoused theories supporting the causative role of multiple somatic mutations in the etiology and persistence of numerous types of cancer. In light of the relatively high somatic mutational rates of mtDNA, the multi-modal coding mechanisms provided by cell-specific patterns of mtDNA heteroplasmy may reflect the evolutionary linkages of mitochondria to primordial protobacterial precursors and trillions of enteric bacteria contained within the human microbiome ( 20 , 34 – 36 ). As a corollary, cellular processes that regulate physiologically compatible patterns of heteroplasmic mtDNA may undergo state-dependent dysregulation resulting in an altered metabolically compromised phenotype characteristic of cancer cells and other pathophysiologically altered cell types ( 22 , 37 ).…”

Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders

“…Finally, dysbiosis of essential strains of gut microflora engendered by dysregulation of biogenic amine signaling pathways may negatively affect essential gut–CNS communication processes at multiple physiological check points that modulate mitochondrial bioenergetics (Petra et al 2015 ; Reigstad et al 2015 ; Scheperjans et al 2015 ; Snyder et al 2015 ; Wallace and Milev 2017a ; Zheng et al 2016 ; Zhou and Foster 2015 ). Recent studies have attempted to elucidate functional associations of impaired mitochondrial function (Stefano and Kream 2016 ; Tobe 2013 ) and/or dysbiosis of gut microflora in the etiology and/or progression of diverse psychiatric and related medical conditions subsumed under the general rubric of AfSD (Thompson et al 2015 ; Tobe 2013 ).…”