Microbial Ecosystem Therapeutic-2 Intervention in People With Major Depressive Disorder and Generalized Anxiety Disorder: Phase 1, Open-Label Study

Abstract

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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“…Oral administration of Lactobacillus plantarum PS128 led to a significant remission in depressive symptoms of MDD patients [115,116] . Furthermore, the encapsulated microbial therapeutic MET-2, which contains 40 strains of bacteria, was effective in reducing the mean Montgomery–Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scores in MDD patients [117] …”

“…[115,116] Furthermore, the encapsulated microbial therapeutic MET-2, which contains 40 strains of bacteria, was effective in reducing the mean Montgomery-Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scores in MDD patients. [117] Previous studies have found that gut microbiota dysbiosis may participate in the pathogenesis of MDD by regulating multiple molecular metabolic pathways, e.g., carbohydrate, GABA, phenylalanine, and tryptophan. [24,114] Clinicallybased findings provide good evidence for MDD analysis; however, clinical samples are susceptible to confounding factors, such as drugs, diet, and geography.…”

“…CAG:237 [114] phenylalanine, tryptophan, [24,114] glycerophospholipids, and sphingolipids metabolism, [118] as well as the CREB, Ras/MAPK signaling pathways, [119][120][121][122] and endocannabinoid signaling pathway [123] distinguishes the subjects with MDD from those with HC with a high diagnostic accuracy of 96% [113] ; a combinatorial marker panel of these six biomarkers discriminates MDD from healthy controls with high classification power in both the discovery (AUC = 0.98) and validation sets (AUC = 0.90) [114] containing 40 strains of bacteria reduces mean MADRS and GAD-7 scores in MDD patients [117] The references indicated with an asterisk ( * ) represent studies conducted with animals. a-Syn: a-synuclein; function of gut microbiota.…”

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