From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

Abstract

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

“…The human gut microbiota is essential for health by supporting the metabolic, immune and neurological functions of the host (El Kaoutari et al 2013, Honda and Littman 2016, Rogers et al 2016. The ecological landscape of the human gut microbiota is highly complex, and consists of trillions of microorganisms including bacteria, archaea, microeukaryotes and viruses (Sender et al 2016).…”

“…Over 2000 species-level phylotypes (prokaryotes including bacteria and archaea) have been detected for the gut microbiota, with each individual estimated to host at least 160 species (Qin et al 2010, Zoetendal et al 2008. The gut microbiota may impact the well-being of human and susceptibility for diseases by interacting with our metabolic, immune and neurological system (Honda and Littman 2016, Koh et al 2016, Rogers et al 2016. Furthermore, the gut microbiota contributes to a variety of metabolic functions and can be seen as an essential part of our digestive system (El Kaoutari et al 2013).…”

Gut thinking: the gut microbiome and mental health beyond the head

“…The observed links between disturbance of the gut microbiome (dysbiosis) and stress, anxiety, and depression have shifted the research ground for mental disorder [12,44,45]. In response to these emerging findings, probiotics and dietary approaches have been explored in terms of their ability to modulate microbiota and address symptoms [46].…”

Exploring the microbiome in health and disease

“…In rodent models, these factors have been shown to be influenced by diet and the gut microbiota. 308 Over the past few years, accumulating evidence has pointed to the critical role played by bidirectional communication between the gut and the brain in neurological disorders.…”