Draft genomes of 12 Bifidobacterium isolates from human IBD fecal samples.

Twelve Bifidobacterium strains were isolated from fecal samples of inflammatory bowel disease patients and matched "household control" individuals. These include the species Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum.

Compounding Achromobacter Phages for Therapeutic Applications.

Achromobacter species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by Achromobacter xylosoxidans CF418 or Achromobacter ruhlandii CF116 experienced fatal exacerbations. Achromobacter spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of Achromobacter. In this study, thirteen lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Achromobacter Kumeyaay phage collection. Six distinct Achromobacter phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available Achromobacter phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 Achromobacter clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in Achromobacter xylosoxidans CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as Achromobacter phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 109 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill Achromobacter spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.

Host interactions of novel Crassvirales species belonging to multiple families infecting bacterial host, Bacteroides cellulosilyticus WH2.

Bacteroides, the prominent bacteria in the human gut, play a crucial role in degrading complex polysaccharides. Their abundance is influenced by phages belonging to the Crassvirales order. Despite identifying over 600 Crassvirales genomes computationally, only few have been successfully isolated. Continued efforts in isolation of more Crassvirales genomes can provide insights into phage-host-evolution and infection mechanisms. We focused on wastewater samples, as potential sources of phages infecting various Bacteroides hosts. Sequencing, assembly, and characterization of isolated phages revealed 14 complete genomes belonging to three novel Crassvirales species infecting Bacteroides cellulosilyticus WH2. These species, Kehishuvirus sp. 'tikkala' strain Bc01, Kolpuevirus sp. 'frurule' strain Bc03, and 'Rudgehvirus jaberico' strain Bc11, spanned two families, and three genera, displaying a broad range of virion productions. Upon testing all successfully cultured Crassvirales species and their respective bacterial hosts, we discovered that they do not exhibit co-evolutionary patterns with their bacterial hosts. Furthermore, we observed variations in gene similarity, with greater shared similarity observed within genera. However, despite belonging to different genera, the three novel species shared a unique structural gene that encodes the tail spike protein. When investigating the relationship between this gene and host interaction, we discovered evidence of purifying selection, indicating its functional importance. Moreover, our analysis demonstrated that this tail spike protein binds to the TonB-dependent receptors present on the bacterial host surface. Combining these observations, our findings provide insights into phage-host interactions and present three Crassvirales species as an ideal system for controlled infectivity experiments on one of the most dominant members of the human enteric virome. Impact statement: Bacteriophages play a crucial role in shaping microbial communities within the human gut. Among the most dominant bacteriophages in the human gut microbiome are Crassvirales phages, which infect Bacteroides. Despite being widely distributed, only a few Crassvirales genomes have been isolated, leading to a limited understanding of their biology, ecology, and evolution. This study isolated and characterized three novel Crassvirales genomes belonging to two different families, and three genera, but infecting one bacterial host, Bacteroides cellulosilyticus WH2. Notably, the observation confirmed the phages are not co-evolving with their bacterial hosts, rather have a shared ability to exploit similar features in their bacterial host. Additionally, the identification of a critical viral protein undergoing purifying selection and interacting with the bacterial receptors opens doors to targeted therapies against bacterial infections. Given Bacteroides role in polysaccharide degradation in the human gut, our findings advance our understanding of the phage-host interactions and could have important implications for the development of phage-based therapies. These discoveries may hold implications for improving gut health and metabolism to support overall well-being. Data summary: The genomes used in this research are available on Sequence Read Archive (SRA) within the project, PRJNA737576. Bacteroides cellulosilyticus WH2, Kehishuvirus sp. 'tikkala' strain Bc01, Kolpuevirus sp. ' frurule' strain Bc03, and 'Rudgehvirus jaberico' strain Bc11 are all available on GenBank with accessions NZ_CP072251.1 ( B. cellulosilyticus WH2), QQ198717 (Bc01), QQ198718 (Bc03), and QQ198719 (Bc11), and we are working on making the strains available through ATCC. The 3D protein structures for the three Crassvirales genomes are available to download at doi.org/10.25451/flinders.21946034.

Host interactions of novel Crassvirales species belonging to multiple families infecting bacterial host, Bacteroides cellulosilyticus WH2.

Bacteroides, the prominent bacteria in the human gut, play a crucial role in degrading complex polysaccharides. Their abundance is influenced by phages belonging to the Crassvirales order. Despite identifying over 600 Crassvirales genomes computationally, only few have been successfully isolated. Continued efforts in isolation of more Crassvirales genomes can provide insights into phage-host-evolution and infection mechanisms. We focused on wastewater samples, as potential sources of phages infecting various Bacteroides hosts. Sequencing, assembly, and characterization of isolated phages revealed 14 complete genomes belonging to three novel Crassvirales species infecting Bacteroides cellulosilyticus WH2. These species, Kehishuvirus sp. 'tikkala' strain Bc01, Kolpuevirus sp. 'frurule' strain Bc03, and 'Rudgehvirus jaberico' strain Bc11, spanned two families, and three genera, displaying a broad range of virion productions. Upon testing all successfully cultured Crassvirales species and their respective bacterial hosts, we discovered that they do not exhibit co-evolutionary patterns with their bacterial hosts. Furthermore, we observed variations in gene similarity, with greater shared similarity observed within genera. However, despite belonging to different genera, the three novel species shared a unique structural gene that encodes the tail spike protein. When investigating the relationship between this gene and host interaction, we discovered evidence of purifying selection, indicating its functional importance. Moreover, our analysis demonstrated that this tail spike protein binds to the TonB-dependent receptors present on the bacterial host surface. Combining these observations, our findings provide insights into phage-host interactions and present three Crassvirales species as an ideal system for controlled infectivity experiments on one of the most dominant members of the human enteric virome.

Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) refers to 2 chronic inflammatory diseases of the intestine, ie, ulcerative colitis and Crohn's disease. IBD results from environmental factors (eg, bacterial antigens) triggering a dysregulated immune response in genetically predisposed hosts. Although the basis of IBD is incompletely understood, a number of recent studies have implicated defective innate immune responses in the pathogenesis of IBD. In this regard, there is much interest in therapies that activate innate immunity (eg, recombinant granulocyte-macrophage colony-stimulating factor). METHODS: In this study, we screened expression and function of circulating leukocyte granulocyte-macrophage colony-stimulating factor receptor (CD116) messenger RNA and surface protein in 52 IBD patients and 52 healthy controls. RESULTS: Our results show that both granulocyte and monocyte CD116 levels, but not CD114 or interleukin-3Rα, were significantly decreased in IBD compared to control (P<.001) and disease controls (irritable bowel syndrome; P<.001; rheumatoid arthritis; P<.025). IBD-associated CD116 repression was more prominent in patients with ulcerative colitis compared to Crohn's disease (P<.05), was independent of disease activity (P>.05), and was not influenced by current medications (P>.05). Receiver operating characteristic curve analysis revealed that leukocyte CD116 expression is a sensitive (85%) and specific (92%) biomarker for IBD. Moreover, granulocyte CD116-mediated function (phosphorylation of signal transducers and activators of transcription 3) paralleled decreased expression of CD116 in IBD granulocytes compared to control (P<.001). CONCLUSIONS: These studies identify defective expression and function of CD116 as a distinguishing feature of IBD and implicate an associated defect in innate immune responses toward granulocyte-macrophage colony-stimulating factor.

Addressing the Long-Term Care Crisis: Identifying Opportunities for Improvement Using Rapid Reviews.

Background: Long-term care (LTC) facilities require urgent, evidence-based care renewal. During 2020 three medical student-driven research projects aiming to study care satisfaction, patient care team dynamics, and advance care directive effectiveness in a local LTC facility required a marked shift in approach due to COVID-19 regulations. Methods: All three projects were re-invented as rapid reviews from their initial designs intended to provide a baseline for quality improvement projects. English-limited PubMed searches for publications within the past 10 years were undertaken. Review articles were prioritized and supplemented by individual studies. Students reviewed the initial abstracts, reviewed them with a supervisor/mentor, assessed the articles for quality, and synthesized major themes. Results: A total of 52 publications were evaluated for the final synthesis of all three projects. Relevant information was retrieved for all three areas, suitable for local evaluation/intervention at micro, meso, and macro policy levels. Conclusions: Rapid reviews of issue-specific, long-term care literature are low resource avenues towards coordinated care improvement. They may also serve as rapid means for regular policy updates while providing next-generation care providers with improved LTC perspectives.

Level of fellowship training increases adenoma detection rates.

BACKGROUND & AIMS: The adenoma detection rate (ADR) is critical to the success of colonoscopy for colorectal cancer screening. The effects of involving gastroenterology fellows in screening colonoscopies are uncertain. We assessed the effects of gastroenterology fellow participation on ADR and whether outcomes vary with year of fellowship training. METHODS: We performed a retrospective review of all average-risk screening colonoscopies performed from April 2005-April 2007 at the University of Colorado Hospital. A gastroenterology attending physician alone performed 2895 colonoscopies; 699 were performed by a gastroenterology fellow supervised by an attending physician. Statistical analyses of polyp, adenoma, and advanced adenoma (or cancer) detection were performed by using logistic regression. RESULTS: The ADR was significantly higher (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.10-1.59) among colonoscopies that included a gastroenterology fellow compared with those performed by only a gastroenterology attending physician. Similarly, the polyp detection rate was higher (OR, 1.28; 95% CI, 1.08-1.52) among colonoscopies involving a gastroenterology fellow. There was no difference in the detection of advanced adenomas or cancers (OR, 1.05; 95% CI, 0.77-1.44) among colonoscopies involving a gastroenterology fellow. The ADR differed greatly by year of training. Compared with colonoscopies performed by an attending gastroenterologist alone, the ADR increased with each year of training: OR, 0.89 (95% CI, 0.66-1.22) for first-year fellows; OR, 1.31 (95% CI, 0.89-1.93) for second-year fellows; and OR, 1.70 (95% CI, 1.33-2.17) for third-year fellows. CONCLUSIONS: Involvement of fellows in screening colonoscopies increases the ADR, primarily because of the increased ADR in procedures involving third-year gastroenterology fellows.

The role of parenteral nutrition in acute leukemia.

Patients with acute leukemia who undergo hematopoietic stem cell transplantation (HSCT) are susceptible to malnutrition caused by several factors including intensive cytotoxic therapy. This paper discusses the significance of malnutrition in these patients and provides an overview of nutrition therapy by the oral, enteral, and parenteral routes. The goal is to investigate whether the use of parenteral nutrition (PN) produces improved clinical outcomes in patients with acute leukemia and to identify criteria for the selection of patients most likely to benefit from this therapy. Although PN may be appropriate for patients suffering from complications such as graft-versus-host disease (GVHD) and mucositis, the data available at this time do not support PN as first-line therapy for all recipients of HSCT.