Steroids, stress and the gut microbiome‐brain axis

Abstract

It is becoming well established that the gut microbiome has a profound impact on human health and disease. In this review, we explore how steroids can influence the gut microbiota and, in turn, how the gut microbiota can influence hormone levels.Within the context of the gut microbiome-brain axis, we discuss how perturbations in the gut microbiota can alter the stress axis and behaviour. In addition, human studies on the possible role of gut microbiota in depression and anxiety are examined. Finally, we present some of the challenges and important questions that need to be addressed by future research in this exciting new area at the intersection of steroids, stress, gutbrain axis and human health. K E Y W O R D Sandrogen, microbiota, oestrogen, steroid hormones, stress | INTRODUCTIONWithin each human gastrointestinal tract, there is an exclusive combination of different communities of organisms, including bacteria, viruses, archaea, protozoa and fungi, which are collectively referred to as the gut microbiota and outnumber the total amount of human cells in the human body.1 The collection of these microorganisms, their genomes and the factors that they produce are all part of the gut microbiome. 2 Increasing evidence suggests that these microorganisms actively participate in shaping and maintaining our physiology almost as an extra organ. ranging from obesity 7 and asthma 8 to a variety of brain disorders. 3,9-14The gut microbiota helps break down food and, in doing so, produces metabolites that can directly influence the physiology of host cells, including brain cells. Moreover, immune responses to pathogenic bacteria produce cytokines and lymphokines that can affect brain physiology. 15Because the nervous system is a master regulator of host function, this allows microbes to influence a broad range of complex physiologicalprocesses. An improved mechanistic understanding of how bacterial molecules act on the nervous system could yield improved therapeutics for treating behavioural and neurological disorders. 16The human gut microbiota is usually stable and resilient to transient perturbations. 17 However, microbial composition or activity of the gut can be modified by a variety of factors, including internal factors such as hormonal changes, or external factors such as diet, antibiotics and stress. 3,18 In this review, the influence of steroids and stress on the gut microbiome-brain axis is discussed, as well as the challenges that face future research in this area. | STEROID HORMONES INFLUENCE THE GUT MICROBIOTAThere is mounting evidence that steroid hormones can affect the gut microbiota. In support of steroids influencing the gut bacterial communities, sex differences have been noted in the composition of the gut microbiota, with specific phyla, family and genera variances occurring with clear effects of gonadectomy and hormone replacement on gut bacteria in rodents. [19][20][21] In mice, the sex differences in the gut microbiota observed between males and females are decreased after castration, indicating a...

Influence of Early Life, Diet, and the Environment on the Microbiome

“…109,110 Therefore, real or perceived stress can modulate this bidirectional communication in a way that increases dysbiosis and increases an individual’s propensity to develop disease. 111,112 For example, stress can trigger the flight or fight response, increasing the production of corticotropin-releasing-hormone and catecholamine production from the central nervous system (CNS) which then modulates gut microbiome function. 112,113 On the other hand, bottom up processes involving release of microbial products such as tryptophan or serotonin during stressful events can contribute to the enteric dysbiosis, increased intestinal permeability and the release of certain neurotransmitters associated with certain diseases.…”

Perceived Stress in First-Year Medical Students and its Effect on Gut Microbiota

“…Prior work in the field of metagenomics has emphasized the role of microbiome stability on host physiology (Lozupone et al, 2012;Faith et al, 2013;Mehta et al, 2018;Tetel et al, 2018). What we found in this study was that phylogenetic assembly of longitudinal participant data by microbiome state may be an option to identify participants experiencing microbiome disruption events.…”

“…What we found in this study was that phylogenetic assembly of longitudinal participant data by microbiome state may be an option to identify participants experiencing microbiome disruption events. There are two proposed mechanisms of how microbiome function may be a feature of stress resilience, in which the microbiome may act through bottom up or top down effects contributing to the observed stress phenotype (Foster et al, 2017;Tetel et al, 2018). In the top down hypothesis, the physiologic effects of stress changes the innervation of the gastrointestinal system, leading to a new physiological state and ultimately to novel niche selection within the gut lumen (Kelly et al, 2015).…”

Cortisol-induced signatures of stress in the fish microbiome

“…Recent research has revealed the diverse influence of microbiota and their metabolites on many aspects of host health and fitness, including digestion and nutrient uptake, metabolism and immune development (Hooper et al 2012; Rea et al 2016). In mammals, stress is well known to disrupt the diversity, structure and function of the microbiome which, in turn, has been associated with long term health effects in the host, including metabolic and immune impairment, and a range of diseases (Foster et al 2017; Tetel et al 2018). The mechanisms by which stress impacts the microbiome are complex, and not fully understood.…”