There is a growing emphasis on the relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and brain health. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the brain, glands, gut, immune cells, and gastrointestinal microbiota that communicate in a complex multidirectional manner to maintain homeostasis. Changes in this environment may contribute to the neuroprogression of stress-related disorders by altering physiological processes including hypothalamic-pituitary-adrenal axis activation, neurotransmitter systems, immune function, and inflammatory responses. While appropriate, coordinated physiological responses, such as immune or stress responses, are necessary for survival, the contribution of repeated or chronic exposure to stress may predispose individuals to a more vulnerable state leaving them more susceptible to stress-related disorders. In this chapter, the involvement of the gastrointestinal microbiota in stress- and immune-mediated modulation of neuroendocrine, immune, and neurotransmitter systems and the consequential behavior is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in the effects of the microbiota-gut-brain axis on the neuroprogression of stress-related disorders as a consequence of neuroinflammatory processes.