Differential Response and Recovery Dynamics of HSPC Populations Following Infection.

Severe infections such as malaria are on the rise worldwide, driven by both climate change and increasing drug resistance. It is therefore paramount that we better understand how the host responds to severe infection. Hematopoiesis is particularly of interest in this context because hematopoietic stem and progenitor cells (HSPCs) maintain the turnover of all blood cells, including all immune cells.

Sleeve Gastrectomy Protects Against Hypertension in Rats due to Changes in the Gut Microbiome.

Introduction: Sleeve gastrectomy (SG), results in improvement in hypertension. We have previously published that rodent SG improves hypertension independent of weight loss associated with unique shifts in the gut microbiome. We tested if the gut microbiome directly improves blood pressure by performing fecal material transfer (FMT) from post-SG rats to surgery-naïve animals.

Differences in intestinal bacteria in traumatic injury survivors with and without probable posttraumatic stress disorder.

Background: Posttraumatic stress disorder (PTSD) is a common consequence of traumatic injury, yet certain biological factors contributing to PTSD are poorly understood. The gut microbiome may influence mental health outcomes, but its role in heterogeneous PTSD presentations requires elucidation.

Methods: Bacterial composition was examined in adults 2-4 years post-trauma with probable PTSD (n = 24) versus trauma-exposed controls without probable PTSD (n = 24).

Reciprocal regulation of enterococcal cephalosporin resistance by products of the autoregulated yvcJ-glmR-yvcL operon enhances fitness during cephalosporin exposure.

Enterococci are commensal members of the gastrointestinal tract and also major nosocomial pathogens. They possess both intrinsic and acquired resistance to many antibiotics, including intrinsic resistance to cephalosporins that target bacterial cell wall synthesis. These antimicrobial resistance traits make enterococcal infections challenging to treat.

A serum-induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease.

Objective: Pediatric nonalcoholic fatty liver disease (NAFLD) is a growing problem, but its underlying mechanisms are poorly understood. We used transcriptomic reporter cell assays to investigate differences in transcriptional signatures induced in hepatocyte reporter cells by the sera of children with and without NAFLD.

Methods: We studied serum samples from 45 children with NAFLD and 28 children without NAFLD.

Thiocillin contributes to the ecological fitness of ATCC 14579 during interspecies interactions with .

The soil-dwelling delta-proteobacterium is a model organism to study predation and competition. preys on a broad range of bacteria mediated by lytic enzymes, exopolysaccharides, Type-IV pilus-based motility, and specialized metabolites. Competition between and prey bacterial strains with various specialized metabolite profiles indicates a range of fitness, suggesting that specialized metabolites contribute to prey survival.

The intestinal microbiome of children with initial and recurrent nephrolithiasis: A pilot study and exploratory analysis.

Introduction: Kidney stone disease in children is rising disproportionate to the general population, representing a disease population with a distinct biological mechanism as compared to adults. Factors influencing recurrent kidney stone disease in children are poorly characterized and the associations of the intestinal microbiome within sub-populations of kidney stone formers, however, are not well described. We evaluated a pilot cohort of children with nephrolithiasis comparing patients based on recurrent kidney stone episodes and abnormal 24-h urinary parameters, with dual aims to compare the microbiome signal in children with initial and recurrent nephrolithiasis and to explore additional associations in microbiome composition and diversity within this population.

Impact of auricular percutaneous electrical nerve field stimulation on gut microbiome in adolescents with irritable bowel syndrome: A pilot study.

Objectives: Percutaneous electrical nerve field stimulation (PENFS) has documented efficacy for irritable bowel syndrome (IBS) via plausible vagal neuromodulation effects. The vagus nerve may affect gut microbiome composition via brain-gut-microbiome signaling. We aimed to investigate gut microbiome alterations by PENFS therapy in adolescent IBS patients.

Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape.

Succinate produced by the commensal protist () stimulates chemosensory tuft cells, resulting in intestinal type 2 immunity. Tuft cells express the succinate receptor SUCNR1, yet this receptor does not mediate antihelminth immunity nor alter protist colonization. Here, we report that microbial-derived succinate increases Paneth cell numbers and profoundly alters the antimicrobial peptide (AMP) landscape in the small intestine.

Gut microbiota and metabolites drive chronic sickle cell disease pain.

Pain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain.

The CKS1/CKS2 Proteostasis Axis Is Crucial to Maintain Hematopoietic Stem Cell Function.

Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic, and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification, and degradation-broadly termed protein homeostasis or "proteostasis"-in these cells is still in its infancy, with very little known about how the functional state of the proteome is maintained in hematopoietic stem cells.

299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats.

The increasing incidence of Type 1 diabetes has coincided with the emergence of the low-fiber, high-gluten Western diet and other environmental factors linked to dysbiosis. Since 299 v (Lp299v) supplementation improves gut barrier function and reduces systemic inflammation, we studied its effects in spontaneously diabetic DR rats provided a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD). All rats provided ND developed diabetes (62.

Group 3 innate lymphoid cells require BATF to regulate gut homeostasis in mice.

Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s and ILC3-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3 homeostasis in the gut.

A single, peri-operative antibiotic can persistently alter the post-operative gut microbiome after Roux-en-Y gastric bypass.

Introduction: Roux-en-Y gastric bypass (RYGB) significantly alters the gut microbiome and may be a mechanism for post-operative cardiovascular disease improvement. We have previously found an association between the class of peri-operative, intravenous antibiotic administered at the time of RYGB and the resolution rate of hypertension suggesting the gut microbiome as a mechanism. In this study, we performed a prospective study of RYGB to determine if a single intravenous antibiotic could alter the gastrointestinal microbial composition.

A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome.

Background: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach.

Methods: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction.

Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study.

The incidence of type 1 diabetes (T1D) has increased, coinciding with lifestyle changes that have likely altered the gut microbiota. Dysbiosis, gut barrier dysfunction, and elevated systemic inflammation consistent with microbial antigen exposure, have been associated with T1D susceptibility and progression. A 6-week, single-arm, open-label pilot trial was conducted to investigate whether daily multi-strain probiotic supplementation could reduce this familial inflammation in 25 unaffected siblings of T1D patients.

Nicotinamide Riboside-Conditioned Microbiota Deflects High-Fat Diet-Induced Weight Gain in Mice.

The gut microbiome plays an essential role in host energy homeostasis and influences the development of obesity and related conditions. Studies demonstrate that nicotinamide riboside (NR) supplementation for diet-induced obesity (DIO) reduces weight gain and increases energy expenditure in mice. NR is a vitamin B derivative and an NAD precursor with potential for treating human diseases arising from mitochondrial degeneration, including obesity and type 2 diabetes.

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice.

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined.

Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production.

Human rhinovirus (RV) is the most common cause of upper respiratory tract infection (URTI) and chronic airway disease exacerbation. Cough is present in 50-80% of URTI cases, accompanied by heightened airway hypersensitivity, yet no effective treatment currently exists for this infectious cough. The mechanism by which RV causes cough and airway hypersensitivity in URTI is still unknown despite recent advances in potential therapies for chronic cough.

Sleeve gastrectomy prevents hypertension associated with unique shifts in the gut microbiome.

Introduction: Bariatric surgery results in resolution of hypertension in over 50% of patients. While weight loss is a critical component to hypertension resolution after bariatric surgery, there may also be weight loss-independent mechanisms.

Objectives: We hypothesized that sleeve gastrectomy (SG) initiates changes in the gut microbiome which reduce postoperative blood pressure.

Identifying priorities and developing strategies for building capacity in amputation research in Canada.

Background: Compared to other patient population groups, the field of amputation research in Canada lacks cohesion largely due to limited funding sources, lack of connection among research scientists, and loose ties among geographically dispersed healthcare centres, research institutes and advocacy groups. As a result, advances in clinical care are hampered and ultimately negatively influence outcomes of persons living with limb loss.

Objective: To stimulate a national strategy on advancing amputation research in Canada, a consensus-workshop was organized with an expert panel of stakeholders to identify key research priorities and potential strategies to build researcher and funding capacity in the field.