Targeting the microbiome-gut-brain axis for improving cognition in schizophrenia and major mood disorders: A narrative review.
08 Mar 2021-Progress in Neuro-psychopharmacology & Biological Psychiatry (Elsevier)-Vol. 105, pp 110130-110130
TL;DR: Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.
Abstract: Cognitive impairment has been consistently found to be a core feature of serious mental illnesses such as schizophrenia and major mood disorders (major depression and bipolar disorder). In recent years, a great effort has been made in elucidating the biological causes of cognitive deficits and the search for new biomarkers of cognition. Microbiome and gut-brain axis (MGB) hormones have been postulated to be potential biomarkers of cognition in serious mental illnesses. The main aim of this review was to synthesize current evidence on the association of microbiome and gut-brain hormones on cognitive processes in schizophrenia and major mood disorders and the association of MGB hormones with stress and the immune system. Our review underscores the role of the MGB axis on cognitive aspects of serious mental illnesses with the potential use of agents targeting the gut microbiota as cognitive enhancers. However, the current evidence for clinical trials focused on the MGB axis as cognitive enhancers in these clinical populations is scarce. Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.
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TL;DR: In this article, the relevance of microbiome alterations in the polyriboinosinic-polyribocytidylic (PolyI:C) mouse model to human schizophrenia was explored.
Abstract: Background Immunopathological concepts have been intensively discussed for schizophrenia. The polyriboinosinic–polyribocytidylic (PolyI:C) mouse model has been well validated to invasively study this disease. The intestinal microbiome exhibits broad immunological and neuronal activities. The relevance of microbiome alterations in the PolyI:C model to human schizophrenia should be explored. Methods Feces of offspring from mice mothers, who were administered to PolyI:C or NaCl (controls) at ED 9, were collected at PND 30 and 180 (PolyI:C and control mice (N = 32 each; half males and females). This was analyzed for bacterial 16S ribosomal DNA (rDNA) using a gut microbiome polymerase chain reaction (PCR) microarray tool. Results Differences were found in species richness of microbiome between animals of different ages (PND 30 and 180), but also between offspring from PolyI:C vs. NaCl treated mothers. In female mice at PND 30, the abundance of Prevotellaceae and Porphyromonadaceae was lower and that of Lactobacillales was higher, whereas in male mice at the same time point the abundance of four families of the Firmicutes phylum (Clostridia vadinBB60 group, Clostridiales Family XIII, Ruminococcaceae and Erysipelotrichaceae) was increased relative to the control group. Limitations No further analyses of cell types or cytokines involved in autoimmune gut and brain processes. Conclusions These finding seem to be similar to microbiome disturbances in patients with schizophrenia. The differential bacterial findings at day 30 (i.e., similar to the prodromal phase in patients with schizophrenia) correspond to the tremendous activation of the immune system with a strong increase in microglial cells which might be responsible for neuroplasticity reduction in cortical areas in patients with schizophrenia.
15 citations
TL;DR: In this article, the authors discuss the ways severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially disrupts the gut-brain-lung axis.
Abstract: The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID-19) pandemic. Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms, including fever, cough, fatigue, and loss of smell and taste. However, many individuals develop pneumonia, acute respiratory distress syndrome, septic shock, and multiorgan dysfunction. In addition to these primarily respiratory symptoms, SARS-CoV-2 can also infiltrate the central nervous system, which may damage the blood-brain barrier and the neuron's synapses. Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves, leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions. Additionally, SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier. As a result, this exacerbates pro-inflammatory responses both locally and systemically, resulting in impaired clinical outcomes. Recent evidence has highlighted the complex interactions that mutually modulate respiratory, neurological, and gastrointestinal function. In this review, we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis. We further highlight targeting specific responses to SARS-CoV-2 for the development of novel, urgently needed therapeutic interventions. Finally, we propose a prospective related to the individuals from Low- and Middle-Income countries. Here, the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.
9 citations
TL;DR: In this paper , a review summarizes the importance and involvement of probiotics and diet in neuroprotection and managing representative neurological disorders, injuries and mood states, and concludes that probiotics could be considered an adjunct therapy to manage metabolic and psychiatric diseases.
Abstract: Alzheimer’s (AD) and Parkinson’s diseases (PD) are common in older people. Autism spectrum disorders (ASD), anxiety, depression, stress, and cognitive impairment are prevalent among people irrespective of age. The incidence of neurological disorders has been increasing in recent decades. Communication between the gut microbiota and the brain is intrinsically complicated, and it is necessary for the maintenance of the gut, brain, and immune functions of the host. The bidirectional link among the gut, gut microbiota and the brain is designated as the “microbiota–gut–brain axis.” Gut microbiota modulates the host immune system and functions of tissue barriers such as gut mucosa and blood–brain barrier (BBB). Gut microbial dysfunction disturbs the gut–brain interplay and may contribute to various gut disorders, neurocognitive and psychiatric disorders. Probiotics could protect intestinal integrity, enhance gut functions, promote intestinal mucosal and BBB functions, and support the synthesis of brain-derived neurotrophic factors, which enhance neuronal survival and differentiation. Probiotics could be considered an adjunct therapy to manage metabolic and psychiatric diseases. Predominantly, Lactobacillus and Bifidobacterium strains are documented as potent probiotics, which help to maintain the bidirectional interactions between the gut and brain. The consumption of probiotics and probiotics containing fermented foods could improve the gut microbiota. The diet impacts gut microbiota, and a balanced diet could maintain the integrity of gut–brain communication by facilitating the production of neurotrophic factors and other neuropeptides. However, the beneficial effects of probiotics and diet might depend upon several factors, including strain, dosage, duration, age, host physiology, etc. This review summarizes the importance and involvement of probiotics and diet in neuroprotection and managing representative neurological disorders, injuries and mood states.
9 citations
30 Apr 2021
TL;DR: The following review presents the objective of developing a search in various sources of information on the relevance of food and nutrition for the maintenance and balance of the microbiota in older people and mentions some contributions from new research.
Abstract: The global demographic transition has allowed to identify a growing increase in the population over 60 years old, which entails the need to generate policies, programs or actions that preserve or improve the quality of life of people at this stage of life. A balanced and sufficient diet guarantees an integral well-being; however, globalization has permeated the conceptions of a healthy diet, a situation that has favored the presence of malnutrition and, therefore, the deterioration of systems and organs including the gastrointestinal tract. In care for elderly aging, gastrointestinal health is of outstanding importance, due to the role that the microbiota is currently recognized in the gut-brain axis, in the modulation of the immune system and in the etiology of inflammatory, neurodegenerative or mental health diseases. The following review presents the objective of developing a search in various sources of information on the relevance of food and nutrition for the maintenance and balance of the microbiota in older people. Among their results, general concepts about the microbiota and the intertwining that is generated with nutrition and food are recognized. On the above, the review focuses on the role of the microbiota in older people, mentions some contributions from new research and ends with reflections about the importance of incorporating microbiota care in maintaining healthy lifestyles.
7 citations
6 citations
References
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TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Abstract: The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
10,126 citations
TL;DR: The long-term effect of the physiologic response to stress is reviewed, which I refer to as allostatic load, which is the ability to achieve stability through change.
Abstract: Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .
5,932 citations
TL;DR: The emerging concept of a microbiota–gut–brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
Abstract: Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
3,058 citations
TL;DR: It is demonstrated that Indigenous spore-forming bacteria from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5- HT to the mucosa, lumen, and circulating platelets and elevating luminal concentrations of particular microbial metabolites increases colonic and blood5-HT in germ-free mice.
2,047 citations
TL;DR: Exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation, and results suggest that commensal microbiota can affect the postnatal development of the Hpa stress response in mice.
Abstract: Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. To test the idea that such microbes may affect the development of neural systems that govern the endocrine response to stress, we investigated hypothalamic–pituitary–adrenal (HPA) reaction to stress by comparing germfree (GF), specific pathogen free (SPF) and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not in response to stimulation with ether. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassociation with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced the response to stress. Importantly, the enhanced HPA response of GF mice was partly corrected by reconstitution with SPF faeces at an early stage, but not by any reconstitution exerted at a later stage, which therefore indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of the HPA stress response in mice.
2,023 citations