Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report

Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment

Sound encoding in mutant mice with disrupted action potential generation

Auditory tasks like sound localization or speech recognition require reliable and temporally precise neuronal sound encoding. The neuronal code must accurately preserve signal properties such as intensity and timing. Electrophysiological recordings from single spiral ganglion neuron provide a detailed picture of how auditory sensory information is encoded. Analysis of the response pattern of the cochlear nucleus cells after receiving sensory information encoded at peripheral synapses gives insight into the auditory systems primary processing. Investigation of the response patterns of spiral ganglion neurons and cochlear nucleus cells after mutations in pre- and post-synaptic proteins of inner hair cell ribbon synapse helps to reveal a role of these proteins in synaptic transmission and sound encoding. The synaptic sound encoding and underlying primary mechanisms at the synapses in the central and peripheral auditory system were studied through a combination of in vivo electrophysiology, confocal and high-resolution STED microscopy, and psychophysiological behavioral experiments for the detection of silent gaps in noise and thresholds sensitivity. This thesis investigates the role of four proteins (WRB, otoferlin, ßIV-spectrin, PSD-95) that are crucial for the action potential generation and neuronal sound encoding. WRB was found to regulate the otoferlin expression and localization and hence plays an essential role for inner hair cell exocytosis. Otoferlin was indicated to play a key role in synaptic vesicles replenishment. Its mutation was found to lead to the gap detection impairment in OtofI515T/I515T mice. The gap detection impairment was attributed to the stronger adaptation of acoustically evoked spiral ganglion neuron spike rates, as well as delayed recovery of the sound onset response in spiral ganglion neurons. A similar mechanism might underlie the speech comprehension difficulties in human patients carrying the same mutation. ßIV-spectrin was found to be crucial for the action potential generation in spiral ganglion neuron. PSD-95 in spiral ganglion neuron was indicated to be essential for proper AMPA receptors clustering and their recycling at the post-synaptic membrane and hence plays a role in spikes generation and synaptic sound encoding

Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial

A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov, identifier: NCT02957591