Background: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses. Methods: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria. Results: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n = 8), preclinical with human donors (n = 9), or entirely preclinical (n = 11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients. Conclusion: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.
Background: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses. Methods: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria. Results: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n=7), preclinical with human donors (n=7), or entirely preclinical (n=7). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients. Conclusion: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment.
Background Recent studies have investigated the potential of treatments that modify the gut microbiome, such as fecal microbiota transplantation and probiotics, in individuals with psychiatric illnesses. Objective The aim of this study was to investigate the safety, tolerability, and efficacy of a novel gut microbiome therapeutic, Microbial Ecosystem Therapuetic-2 (MET-2), in people with depression and anxiety. Methods In this phase 1, open-label trial, 12 adults diagnosed with major depressive disorder, generalized anxiety disorder, or both were recruited. Over 8 weeks, participants consumed three capsules per day, orally, of an encapsulated microbial therapeutic (MET-2), which contained 40 strains of bacteria that were purified and lab-grown from the stool of a single healthy donor. Participants were assessed biweekly using clinical scales and questionnaires in order to evaluate the safety, efficacy, and tolerability of the therapeutic. Results The therapeutic was found to be generally safe and tolerable, with limited adverse events and side effects and no serious adverse events. Of the 12 individuals included in this study, 9 (75%) responded to treatment (50% improvement in Montgomery-Asberg Depression Rating Scale [MADRS] scores, 7-item Generalized Anxiety Disorder scale [GAD-7] scores, or both, from baseline to the week-8 visit). Over the course of 10 weeks, MET-2 significantly decreased mean MADRS and GAD-7 scores (MADRS: F2.731, 30.05=8.784, P<.001; GAD-7: F2.778, 30.55= 9.638, P<.001). Multiple comparisons with Bonferroni adjustments showed a significant reduction in MADRS scores from baseline (mean 19.00, SD 4.843) to week 6 (mean 11.25, SD 8.001; P=.009), week 8 (mean 8.667, SD 8.732; P=.002), and week 10 (mean 8.250, SD 9.304; P=.006). Multiple comparisons showed a significant reduction in GAD-7 scores from baseline (mean 13.58, SD 4.010) to week 4 (mean 9.167, SD 5.096; P=.03), week 6 (mean 7.667, SD 4.539; P=.004), week 8 (mean 7.333, SD 6.583; P=.03), and week 10 (mean 7.500, SD 6.448; P=.03). Conclusions The findings from this study are the first to provide evidence for the role of microbial ecosystem therapy in treating depression and anxiety. However, a double-blind, randomized controlled trial with a larger sample size is needed for more conclusive results. Trial Registration ClinicalTrials.gov NCT04052451; https://www.clinicaltrials.gov/ct2/show/NCT04052451 International Registered Report Identifier (IRRID) RR2-10.2196/17223
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