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The Role of the Microbiome on Human Health
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Rodney R. Dietert, Janice M. Dietert
Gut microbiota can communicate with the brain using immune, neuro, and endocrine pathways (Slyepchenko et al. 2014). Probiotics are becoming a useful tool in the treatment of depression and anxiety. Vlainić et al. (2016) described the value in probiotic adjunct therapy for treating major depressive disorder (MDD). Part of the basis for microbiome adjustments in MDD is the fact that the gut microbiome plays a major role both directly and indirectly in the production of neurotransmitters, neuroactive peptides, and glutamatergic and GABAergic transmission (e.g., GABA, serotonin, norepinephrine, dopamine) (Cryan and Dinan 2015). Additionally, the microbiome profile largely determines the balance of pro- and anti-inflammatory cytokines that play a role in MDD (Dinan and Cryan 2016). The control of mood and behavior is so extensive that researchers recently coined the term psychobiotics to refer to mind altering probiotics (Wall et al. 2014). Some gut microbes have the potential to regulate myelination in the prefrontal cortex via changes in gene expression (Hoban et al. 2016). Among the potential candidate probiotics to treat depression and anxiety are: Bifidobacterium longum (B.) 1714 and B. breve 1205 (Savignac et al. 2014).
Probiotics and Depression
Published in Martin Colin R, Derek Larkin, Probiotics in Mental Health, 2018
Psychobiotics is an approach that combines two avenues, namely probiotics and psychiatric illness (Dinan et al., 2013). Dinan et al. (2013) describes psychobiotics as “a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness”. The National Institute of Health in the USA has funded many projects which appear to be yielding promising results. Currently the Human Microbiome Project is funding projects exploring, pregnancy and preterm birth, onset of inflammatory bowel disease, and onset of Type II diabetes. In 2012 Thomas Insel, Director of the National Institute of Mental Health in the USA, referred to the study of macrobiotics “How these differences in our microbial would influence the development of the brain and behavior will be one of the greatest frontiers of clinical neuroscience in the next decade” (Insel, 2012). Research in recent years appears to be yielding promising results which indicate that cognitive and emotional processes can be altered by microbes acting through the brain-gut axis (Dinan et al., 2013; Heijtz et al., 2011).
Stress and the brain-gut axis across the spectrum of digestive disorders
Published in Simon R. Knowles, Laurie Keefer, Antonina A. Mikocka-Walus, Psychogastroenterology for Adults, 2019
These observations have raised the possibility of the use of probiotic supplements as ‘psychobiotics’ to regulate brain function in the setting of mood or pain disorders [38]. In healthy individuals, the use of a combination probiotic preparation including a Lactobacillus and Bifidobacterium species led to significant changes in emotion-affective, viscero-sensory and somato-sensory network responses to an emotional faces recognition task [53]. These changes occurred without any measurable changes in mood on self-report instruments, and without discernible changes to gut microbiota, suggesting the observed benefits were mediated by an effect on inflammatory or neurotransmitter intermediates. In a double-blinded study of a Bifidobacterium probiotic in IBS patients, decreased emotional arousal network responses to negative stimuli were seen on functional magnetic resonance imaging in the probiotic-treated group [54]. Probiotics also hold the potential to modulate CNS function in patients without GI conditions [55]. In a clinical trial of patients with major depression disorder (MDD), a Lactobacillus/Bifidobacterium probiotic significantly lowered depression scores, and also positively impacted insulin resistance and inflammatory markers [56]. Another study of women with post-partum depression demonstrated improvement in both anxiety and depression scores [57]. For more detailed reviews relating to the interactions between microbiota, BGA, mental health, and potential therapeutic interventions, see [58–61]. Figure 5.4 illustrates an overview of the bi-directional interactions, key effectors, and functions of the BGM axis.
Does the gut microbiome mediate antipsychotic-induced metabolic side effects in schizophrenia?
Published in Expert Opinion on Drug Safety, 2022
Svetlina S. Vasileva, Jack Tucker, Dan Siskind, Darryl Eyles
Psychobiotic treatment also has the potential to improve emotional well-being and decrease depression and anxiety. A cross-sectional cohort study in patients with either schizophrenia or bipolar disorder, compared the microbiome of those treated with an SGA and those treated with lithium/lamotrigine [133]. It was found that people treated with SGAs had decreased levels of the members of the Alistipes group from the Bacteroidetes phylum. Females treated with SGAs exhibited reduced α diversity compared to those undertaking lithium treatment, however there was no difference in males. Next, patients on SGA treatment received a resistant starch prebiotic supplementation for 2 weeks. This did not have an effect on weight gain, bacterial α diversity, or mood but was associated with an improvement in the emotional well-being domain, an increase in the Actinobacteria phylum, and a fourfold increase in the resistant starch-degrading species Bifidobacterium faecale and Bifidobacterium adolescentis. The hypothesized probiotic effect on major butyrate-producing bacteria was not observed, and thus it was unclear what mechanisms drove the observed improvement of well-being.
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Published in Gut Microbes, 2020
Aimée Parker, Sonia Fonseca, Simon R. Carding
Probiotic treatments have been associated with modulating mood and anxiety in animal models and humans. The first reported trial of using probiotic bacteria to treat mental health conditions was published in the early 20th century and described the use of lactic acid bacteria to successfully treat melancholia and constipation.194 The term “psychobiotics” has since been coined to describe bacteria which, when ingested in adequate amounts, have a positive mental health effect.140 Several human interventions provided evidence that psychobiotics can alter mental state. The intake of Lactobacillus helveticus and Bifidobacterium longum reduced 24-hour urinary free cortisol, a biomarker for stress response, in healthy volunteers.195 Healthy students consuming fermented milk containing Lactobacillus casei strain Shirota had lower plasma cortisol compared to placebo group on the day before an examination,196 and a probiotic strain of Lactobacillus rhamnosus exhibited a protective effect on symptoms of postpartum depression.197 One possible mechanism for the mood-altering effects of psychobiotics is by enhancing production of neurotransmitters, such as GABA and glutamate which control neural excitation-inhibition balance, and BDNF which is implicated in learning processes and control of fear.198 Another possible mechanism is by altering the balance of circulating pro-and anti-inflammatory cytokines, restoring inflammation-induced BBB permeability, preventing potentially harmful material from entering the brain,199 and promoting mental health and psychological resilience.140
The gut microbiome as a target for adjuvant therapy in obstructive sleep apnea
Published in Expert Opinion on Therapeutic Targets, 2020
Mohammad Badran, Saif Mashaqi, David Gozal
In the past decades, the gut microbiota emerged as a key regulator of the gut-brain axis. Evidence from germ free mice showed that myelination, dendritic growth, neurogenesis, blood brain barrier (BBB), microglia, neurotransmitters, and synaptic plasticity are all affected in the absence of microbiota [103]. Alterations in behavior in animals and humans given specific strains of bacteria, and the long-lasting effects of antibiotics on the brain in early life indicate that the microbiota can exert a considerable influence over host cognitive, mood and behavioral processes [103]. Pathways of communication between the gut microbiota and the brain are bidirectional and include: i) the vagus nerve [104] – Vagotomy can decrease the benefits of L. rhamnosus [105] while enteroendocrine cells can release glutamate that activates the vagal pathways [106]; ii) Intestinal microbiota can generate bioactive molecules including SCFAs that regulate microglial inflammatory responses [107], and modulate neurotransmitter release and activity like dopamine, λ-aminobutyric acid (GABA) and norepinephrine, as well as serotonin (through tryptophan metabolism) [103]; iii) the immune system is considered the most important communication pathway since the intestines contains a condensed concentration of immune cells that produces a variety of inflammatory cytokines, which can be transmitted to the central nervous system (CNS) via the circulatory and nervous systems [108]. Pro-inflammatory cytokines can reach the CNS through the humoral route (via saturable transporters at the BBB), neural route (via afferent neurons), and cellular route (immune cells migrating to the brain vasculature and parenchyma) [109]. CNS inflammation is initiated when the microglia become activated and release pro-inflammatory cytokines including IL-1β, which eventually induces the production of the stress hormone cortisol [110,111]. It is well-documented that inflammation is the main underlying mechanism in many neurodegenerative and neuropsychiatric disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and major depressive disorder (MDD) [112]. Thus, gut dysbiosis can be linked to neurobehavioral disorders [113]. Pre- and probiotics that influence the gut-brain -axis are called ‘psychobiotics’ and a significant number of studies have recently shown anxiolytic, anti-depressant, emotional, and systemic effects, and also beneficial cognitive effects [114].