Keli Yang

Background & AimsProteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn’s disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD.MethodsProteus spp abundance was assessed by ure gene–specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice.ResultsProteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice.ConclusionsP mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD. Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn’s disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD. Proteus spp abundance was assessed by ure gene–specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice. Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.

Manipulation of gut microbiota by bacterial metabolites has shown protective effects against colitis; while the efficacy is strictly limited by the poor oral delivery efficiency and single drug usage. Here, a novel prebiotics and postbiotics synergistic delivery microcapsule composed of indole-3-propionic acid (IPA) postbiotic and three prebiotics including alginate sodium, resistant starch (RS), and chitosan via microfluidic electrospray for preventing and treating colitis are proposed. It is found that oral administration of IPA microcapsules (IPA@MC) to mice can exert significant protective effects to colitis, suggesting the therapeutic synergy between prebiotics and postbiotics. Furthermore, the mechanism of the IPA@MC is revealed in modulating the gut microbiota, that is by significantly increasing the overall richness and abundance of short-chain fatty acids (SCFA) producing bacteria such as Faecalibacterium and Roseburia. These results indicate that the prebiotics and postbiotics synergistic delivery microcapsules are ideal candidates for treating colitis.

Developing advanced biocompatibility materials is of critical importance in biomedical engineering. Polyhydroxyalkanoates (PHA), being famous for its flexible mechanical properties, thermal properties, biocompatibility, and biodegradability, has been widely used in wound dressings, artificial blood vessels, heart valves, nerve conduits, bone and cartilage scaffolds, surgical sutures, and other fields. However, reports on the application of PHA in tissue repair and regeneration are often lacking in systematics. Here, a comprehensive and in-depth perception of the performance advantages and application value of PHA is provided. In this review, the following applications of PHA in biomedical engineering are covered: i) soft tissue, ii) organ tissue, iii) vascular tissue, iv) heart valve tissue, v) nerve conduit tissue, vi) bone tissue, vii) cartilage tissue and viii) others. Finally, an outlook on the future research directions and challenges of PHA is presented.

AIMS: The aim of this study was to study inactivation of different pathogenic bacteria on agar model surface using TiO2-UV photocatalysis (TUVP). METHODS AND RESULTS: A unified food surface model was simulated using Bacto(™) agar, a routinely used microbial medium. The foodborne pathogenic bacteria Escherichia coli K12 (as a surrogate for E. coli O157:H7), Salmonella Typhimurium, Staphylococcus aureus and Listeria monocytogenes were inoculated onto the agar surface, followed by investigation of TUVP-assisted inactivation and morphological changes in bacterial cells. The TUVP process showed higher bacterial inactivation, particularly for Gram-negative bacteria, than UVC alone and a control (dark reaction). A TUVP treatment of 17·2 mW cm(-2) (30% lower than the UVC light intensity) reduced the microbial load on the agar surface by 4·5-6·0 log CFU cm(-2). UVC treatment of 23·7 mW cm(-2) caused 3·0-5·3 log CFU cm(-2) reduction. CONCLUSIONS: The use of agar model surface is effective for investigation of bacterial disinfection and TUVP is a promising nonthermal technique. SIGNIFICANCE AND IMPACT OF THE STUDY: The results showing effects of photocatalysis and other treatments for inactivation of bacterial pathogens on model surface can be useful for applying such processes for disinfection of fruit, vegetables and other similar surfaces.