Although there are number of available therapies for ulcerative colitis (UC), many patients are unresponsive to these treatments or experience secondary failure during treatment. Thus, the development of new therapies or alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis of gut microbiota have been tested in the management of UC due to the unquestionable role of gut microbiota in the etiology of UC. Advanced molecular analyses of gut microbiomes revealed evident dysbiosis in UC patients, characterized by a reduced biodiversity of commensal microbiota. Administration of conventional probiotic strains is a commonly applied approach in the management of the disease to modify the gut microbiome, improve intestinal barrier integrity and function, and maintain a balanced immune response. However, conventional probiotics do not always provide the expected health benefits to a patient. Their benefits vary significantly, depending on the type and stage of the disease and the strain and dose of the probiotics administered. Their mechanism of action is also strain-dependent. Recently, new candidates for potential next-generation probiotics have been discovered. This could bring to light new approaches in the restoration of microbiome homeostasis and in UC treatment in a targeted manner. The aim of this paper is to provide an updated review on the current options of probiotic-based therapies, highlight the effective conventional probiotic strains, and outline the future possibilities of next-generation probiotic and postbiotic supplementation and fecal microbiota transplantation in the management of UC.

The ascomycetous family Chaetomiaceae (class Sordariomycetes) includes numerous soilborn, saprophytic, endophytic and pathogenic fungi which can adapt to various growth conditions and living niches by providing a broad armory of oxidative and antioxidant enzymes. We release the 34.7 Mbp draft genome of Chaetomium cochliodes CCM F-232 consisting of 6036 contigs with an average size of 5756 bp and reconstructed its phylogeny. We show that this filamentous fungus is closely related but not identical to Chaetomium globosum and Chaetomium elatum. We screened and critically analysed this genome for open reading frames coding for essential antioxidant enzymes. It is demonstrated that the genome of C. cochliodes contains genes encoding putative enzymes from all four known heme peroxidase superfamilies including bifunctional catalase-peroxidase (KatG), cytochrome c peroxidase (CcP), manganese peroxidase, two paralogs of hybrid B peroxidases (HyBpox), cyclooxygenase, linoleate diol synthase, dye-decolorizing peroxidase (DyP) of type B and three paralogs of heme thiolate peroxidases. Both KatG and DyP-type B are shown to be introduced into ascomycetes genomes by horizontal gene transfer from various bacteria. In addition, two putative large subunit secretory and two small-subunit typical catalases are found in C. cochliodes. We support our genomic findings with quantitative transcription analysis of nine peroxidase & catalase genes. We delineate molecular phylogeny of five distinct gene superfamilies coding for essential heme oxidoreductases in Chaetomia and from the transcription analysis the role of this antioxidant enzymatic armory for the survival of a peculiar soil ascomycete in various harsh environments.

A bacterial isolate MR-CH-I2 [KC809939] isolated from soil contaminated mainly by high nickel concentrations in southwest Slovakia was previously found carrying ncc A-like heavy-metal resistance determinant, marked as MR-CH-I2-HMR [KF218096]. According to phylogenetic analysis of short (696 bp) 16S rDNA (16S rRNA) sequences this bacterium was tentatively assigned to Uncultured beta proteobacterium clone GC0AA7ZA05PP1 [JQ913301]. ncc A-like gene product was on the same base of its partial (581 bp) sequences tentatively assigned to CzcA family heavy metal efflux pump [YP_001899332] from Ralstonia picketii 12J with 99% similarity. In this study the bacterium MR-CH-I2 and its heavy-metal resistance determinant were more precisely identified. This bacterial isolate was on the base of phylogenetic analysis of almost the whole (1,500 bp) 16S rDNA (16S rRNA) sequence, MR-CH-I2 [MF102046], and sequence for gyr B gene and its product respectively, MR-CH-I2-gyrB [MF134666], assigned to R. picketii 12J [CP001068] with 99 and 100% similarities, respectively. In addition, the whole ncc A-like heavy-metal resistance gene sequence (3,192 bp), marked as MR-CH-I2-nccA [KR476581], was obtained and on the base of phylogenetic analysis its assignment was confirmed to MULTISPECIES: cation efflux system protein CzcA [WP_004635342] from Burkholderiaceae with 98% similarity. Furthermore, although the bacterium carried one high molecular plasmid of about 50 kb in size, ncc A-like gene was not located on this plasmid. Finally, the results from RT-PCR analysis showed that MR-CH-I2-nccA gene was significantly induced only by the addition of nickel.

Fecal microbiota transplantation (FMT) seems to be a promising approach in ulcerative colitis (UC) management with the aim of repopulating a patient’s dysbiotic microbiota with beneficial bacteria and restore its metabolic activity to its healthy characteristics. Metabolites present after FMT may improve the function and integrity of the intestinal barrier, reduce inflammation, and thus induce remission in an UC patient. In this study we evaluated whether the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model may be a suitable non-invasive alternative for studying and modifying the dysbiotic microbiota in UC by FMT application. SHIME® model was used to investigate microbial and metabolic changes in the gut microbiota of UC patient induced by FMT application. FMT-modified metabolites from SHIME® were applied to an in vitro model of the intestinal barrier (differentiated Caco-2 and HT-29-MTX-E12 cell lines) compromised by pro-inflammatory cytokines to study the effect of FMT on the intestinal barrier. Qualitative and quantitative microbial analyses showed that FMT increased the diversity and variability of the microbiota in UC patient associated with a significant increase in total bacteria, Bacteroidota and Lactobacillus, as well as an increase in butyrate levels. In addition, an increase in the relative abundance of some important species such as Faecalibacterium prausnitzii and Bifidobacterium longum was observed, and there was also an enrichment of the microbiota with new species such as Blautia obeum, Roseburia faecis, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans and Eubacterium rectale. Furthermore, microbial metabolites modulated by FMT from the SHIME® model prevented intestinal barrier damage and inhibited interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) secretion when cell barriers were pretreated with FMT medium for 24 h. In summary, this study confirmed that a single dose of FMT beneficially modulated the composition and metabolic activity of the UC microbiota in the SHIME® model. FMT favorably modulates the gut microbiota of UC patient cultured in the SHIME® model. FMT-modulated SHIME-derived microbial metabolites improve intact and inflamed intestinal barrier properties in vitro. Repeated applications are necessary to maintain the beneficial effect of FMT in SHIME® model.