Fecal Microbial and Metabolomic Change during treatment course for depression: An Observational Study.

BACKGROUND: There is growing evidence regarding the connection between alterations in gut microbiota and their metabolites in patients with depressive disorders, suggesting a potential role in pathophysiology. Our study aimed to investigate the relationship between microbial, metabolomic features and the course of treatment for depression in a real-world clinical setting. METHODS: Patients diagnosed with depressive disorders were recruited, and their stool was collected at three time points during their depression treatments. Patients were divided into three groups: non-responders, responders, and stable remitters. Gut microbiomes were analyzed using 16S rRNA gene sequencing, and gut metabolomes were analyzed by a mass spectrometry approach. Microbiomes/metabolomes were compared between groups cross-sectionally and longitudinally. RESULTS: A total of 33 patients were recruited and divided into non-responders (n = 16), responders (n = 11), and stable remitters (n = 6). Non-responders presented lower alpha diversity in the Phylogenic Diversity index compared to responders during the treatment course (p = 0.003). Non-responders presented increased estimated glutamate synthesis functions by the microbiota compared to responders and stable remitters (p = 0.035). There were no specific microbiota or metabolome that differentiated the three groups. LIMITATIONS: Small sample size with no healthy controls. CONCLUSIONS: Our results indicate that both cross-sectional microbial features and longitudinal microbial transitions are different depending on the treatment course of depression. Controlled studies, as well as animal studies, are needed in the future to elucidate the causal relationship between microbiota and depression.

Asymmetric Direct Vinylogous Conjugate Addition of Substituted Furanone Derivatives to Benzoyl Acrylonitrile: Stereoselective Synthesis Toward Bicyclic γ-Lactams.

A diaminomethylenemalononitrile organocatalyst efficiently promotes the asymmetric direct vinylogous conjugate additions of α-angelica lactones to benzoyl acrylonitrile derivatives, resulting in the corresponding addition products bearing vicinal tertiary and quaternary stereogenic centers with excellent enantioselectivities (up to 99% ee). This report is the first successful example of the asymmetric conjugate additions of α-angelica lactone to benzoyl acrylonitriles. The chiral γ,γ-disubstituted γ-butenolides obtained can be readily transformed to the bicyclic γ-lactam derivative as a valuable synthetic intermediate.

Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting.

BACKGROUND: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. METHOD: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. RESULTS: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively). CONCLUSION: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

Synthesis of Chiral γ,γ-Disubstituted γ-Butenolides via Direct Vinylogous Aldol Reaction of Substituted Furanone Derivatives with Aldehydes.

An organocatalyzed method for synthesizing chiral γ,γ-disubstituted γ-butenolides via direct vinylogous aldol reactions of γ-substituted ß,γ-butenolides with aldehydes is reported. This reaction is catalyzed by a squaramide-sulfonamide organocatalyst to afford a range of anti-aldol adducts possessing vicinal quaternary and tertiary stereocenters with high to excellent enantioselectivities (reaching 95% ee). This is the first report of a successful stereoselective direct vinylogous aldol reaction of aldehydes with γ-substituted ß,γ-butenolides.

Two modes of autoregulation of the murR repressor in Escherichia coli.

The murPQ operon of Escherichia coli encoding the enzymes for degradation of MurNAc is derepressed by MurR (YfeT) in the presence of MurNAc-6-phosphate. MurR also represses its own expression. We found that murR is stimulated in rich medium. This activation involves MurR and most of the IIBC components of the phosphotransferase system, suggesting auto-induction of murR by an activated form of MurR.