UNASSIGNED: Neurosteroids have recently gained in interest as a treatment strategy for affective disorders. Etifoxine is known for its dual mode of action, one of which is to stimulate endogenous neurosteroid synthesis. The gut microbiome has been studied in affective disorders, but it has not been investigated in the context of human etifoxine or neurosteroid interventions.
UNASSIGNED: We performed a crossover study with 36 healthy male volunteers who received etifoxine versus alprazolam and placebo in a balanced Williams design. Participants were randomized into six sequences and went through three 5-day treatments followed by wash-out phases of 9 days. Bacterial compositions in stool samples were determined by high-throughput 16S rRNA amplicon sequencing.
UNASSIGNED: Gut microbiome analyses revealed no relevant effects between treatments with respect to alpha and beta diversity. Differential abundance analyses yielded etifoxine treatment as the only effect related to changes in microbial features with reductions of Faecalibacterium duncaniae, Roseburia hominis and Lactobacillus rogosae (i.e., Bacteroides galacturonicus).
UNASSIGNED: Here we report on the first human investigation of the gut microbiome with short-term etifoxine intervention. Differences in diversity and compositional structure of the microbiome were more likely due to between- subject effects rather than medication. However, five-day treatment with etifoxine reduced the abundance of a few bacterial species. These species are currently seen as beneficial components of a healthy intestinal microbiome. This reduction in abundances may be related to elevated endogenous neurosteroids.

Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we establish a gut epithelium-microbe-immune microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), with CD4+ naïve T cells circulating underneath the colonic epithelium. Multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines being secreted into both apical and basolateral compartments. In contrast, the absence of APCs does not allow reliable detection of these cytokines. In the presence of APCs, F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, but no significant change on the secreted cytokines. In contrast, integration of CD4+ naïve T cells reverses this effect by decreasing the transcription of TLR1, IFNA1, and indoleamine 2,3-dioxygenase, and increasing the F. prausnitzii-induced secretion of pro-inflammatory cytokines such as IL-8, MCP-1/CCL2, and IL1A. These results highlight the contribution of individual innate immune cells in the regulation of the immune response triggered by the gut commensal F. prausnitzii. The successful integration of defined populations of immune cells in this gut microphysiological system demonstrated the usefulness of the GuMI physiomimetic platform to study microbe-epithelial-immune interactions in health and disease.

A strain of the recently validated species Faecalibacterium hominis shares 99.0 % 16S rRNA gene sequence similarity with the type strain of Faecalibacterium duncaniae. The aim of this study was to evaluate the taxonomic relationship between F. hominis and F. duncaniae. F. duncaniae JCM 31915T showed 73.0 % digital DNA-DNA hybridization (dDDH) value with F. hominis JCM 39347T. The average nucleotide identity (ANI) value between these two strains was 96.7 %. These results indicate that F. duncaniae JCM 31915T and F. hominis JCM 39347T represent members of the same species. Based on these data, we propose Faecalibacterium hominis as a later heterotypic synonym of Faecalibacterium duncaniae. An emended description is provided.

Faecalibacterium prausnitzii is one of the most important butyrate-producing bacteria in the human gut. Previous studies have suggested the presence of several phylogenetic groups, with differences at the species level, in the species, and a taxonomic re-evaluation is thus essential for further understanding of ecology of the important human symbiont. Here we examine the phenotypic, physiological, chemotaxonomic and phylogenomic characteristics of six F. prausnitzii strains (BCRC 81047T=ATCC 27768T, A2-165T=JCM 31915T, APC918/95b=JCM 39207, APC942/30-2=JCM 39208, APC924/119=JCM 39209 and APC922/41-1T=JCM 39210T) deposited in public culture collections with two reference strains of Faecalibacterium butyricigenerans JCM 39212T and Faecalibacterium longum JCM 39211T. Faecalibacterium sp. JCM 17207T isolated from caecum of broiler chicken was also included. Three strains of F. prausnitzii (BCRC 81047T, JCM 39207 and JCM 39209) shared more than 96.6 % average nucleotide identity (ANI) and 69.6 % digital DNA-DNA hybridization (dDDH) values, indicating that the three strains are members of the same species. On the other hand, the remaining three strains of F. prausnitzii (JCM 31915T, JCM 39208 and JCM 39210T) were clearly separated from the above three strains based on the ANI and dDDH values. Rather, JCM 39208 showed ANI and dDDH values over the cut-off values of species discrimination (>70 % dDDH and >95-96 % ANI) with F. longum JCM 39211T, whereas JCM 31915T, JCM 39210T and JCM 17207T did not share dDDH and ANI values over the currently accepted cut-off values with any of the tested strains, including among them. Furthermore, the cellular fatty acid patterns of these strains were slightly different from other F. prausnitzii strains. Based on the collected data, F. prausnitzii JCM 31915T, F. prausnitzii JCM 39210T and Faecalibacterium sp. JCM 17207T represent three novel species of the genus Faecalibacterium, for which the names Faecalibacterium duncaniae sp. nov. (type strain JCM 31915T=DSM 17677T=A2-165T), Faecalibacterium hattorii sp. nov. (type strain JCM 39210T=DSM 107841T=APC922/41-1T) and Faecalibacterium gallinarum sp. nov. (type strain JCM 17207T=DSM 23680T=ic1379T) are proposed.