Interleukin-17 directly stimulates tumor infiltrating Tregs to prevent cancer development.

Background: Interleukin-17 (IL-17) family cytokines promote protective inflammation for pathogen resistance, but also facilitate autoimmunity and tumor development. A direct signal of IL-17 to regulatory T cells (Tregs) has not been reported and may help explain these dichotomous responses. Methods: We generated a conditional knockout of Il17ra in Tregs by crossing Foxp3-YFP-Cre mice to Il17ra-flox mice (Il17ra ΔTreg mice). Subsequently, we adoptively transferred bone marrow cells from Il17ra ΔTreg mice to a mouse model of sporadic colorectal cancer (Cdx2-Cre +/Apc F/+), to selectively ablate IL-17 direct signaling on Tregs in colorectal cancer. Single cell RNA sequencing and bulk RNA sequencing were performed on purified Tregs from mouse colorectal tumors, and compared to those of human tumor infiltrating Treg cells. Results: IL-17 Receptor A (IL-17RA) is expressed in Tregs that reside in mouse mesenteric lymph nodes and colon tumors. Ablation of IL-17RA, specifically in Tregs, resulted in increased Th17 cells, and exacerbated tumor development. Mechanistically, tumor-infiltrating Tregs exhibit a unique gene signature that is linked to their activation, maturation, and suppression function, and this signature is in part supported by the direct signaling of IL-17 to Tregs. To study pathways of Treg programming, we found that loss of IL-17RA in tumor Tregs resulted in reduced RNA splicing, and downregulation of several RNA binding proteins that are known to regulate alternative splicing and promote Treg function. Conclusion: IL-17 directly signals to Tregs and promotes their maturation and function. This signaling pathway constitutes a negative feedback loop that controls cancer-promoting inflammation in CRC.

Urine output is an early and strong predictor of acute kidney injury and associated mortality: a systematic literature review of 50 clinical studies.

BACKGROUND: Although the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype. METHODS: The systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle-Ottawa Quality Assessment Scale for observational studies. RESULTS: A total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4-46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality. CONCLUSIONS: Evidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI.

A Comparative Analysis of the Efficacy of Local Anesthetics and Systemic Anesthetics in the Red-Headed Versus Non-Red-Headed Patient Population: A Comprehensive Review.

Researchers have found that individuals with red hair often require higher doses of anesthetic medications to achieve the same level of pain relief or sedation compared to people with other hair colors. This review investigates the effects of local and systemic anesthetics in individuals with red hair compared to the general population. Focusing on both local and systemic anesthesia, this research aims to elucidate any distinctive responses or complications among the red-haired demographic. Utilizing a systematic review approach, we analyzed a wide array of previous research papers published over the last two decades to gather relevant data. Our findings suggest that people with red hair may exhibit variations in their response to both local and systemic anesthesia compared to non-red-haired individuals, indicating the necessity for tailored anesthetic approaches in clinical settings. Previous studies have found that individuals with red hair, as well as those with the corresponding melanocortin-1 receptor (MC1R) mutations, exhibit a greater resistance to the effects of systemic and local anesthetics. This review provides valuable insights that could help healthcare professionals optimize anesthetic management and improve patient outcomes, particularly for those with red hair.

Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.

Intestinal ischemic injury damages the epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined. We hypothesized that by identifying a subpopulation of restituting enterocytes by their expression of cell migration transcriptional pathways, we can then predict novel upstream regulators of age-dependent restitution response programs. Superficial mucosal epithelial cells from recovering ischemic jejunum of juvenile pigs were processed for single cell RNA sequencing analysis, and predicted upstream regulators were assessed in a porcine intestinal epithelial cell line (IPEC-J2) and banked tissues. A subcluster of absorptive enterocytes expressed several cell migration pathways key to restitution. Differentially expressed genes in this subcluster predicted their upstream regulation included colony stimulating factor-1 (CSF-1). We validated age-dependent induction of CSF-1 by ischemia and documented that CSF-1 and CSF1R co-localized in ischemic juvenile, but not neonatal, wound-adjacent epithelial cells and in the restituted epithelium of juveniles and rescued (but not control) neonates. Further, the CSF1R inhibitor BLZ945 reduced restitution in scratch wounded IPEC-J2 cells. These studies validate an approach to inform potential novel therapeutic targets, such as CSF-1, to improve outcomes in neonates with intestinal injury in a unique pig model. NEW & NOTEWORTHY: These studies validate an approach to identify and predict upstream regulation of restituting epithelium in a unique pig intestinal ischemic injury model. Identification of potential molecular mediators of restitution, such as CSF-1, will inform the development of targeted therapeutic interventions for medical management of patients with ischemia-mediated intestinal injury.

The tidyomics ecosystem: enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis and integration. Addressing these challenges, Bioconductor provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming offers a revolutionary data organization and manipulation standard. Here we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analyzing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas, spanning six data frameworks and ten analysis tools.

Association between switching to integrase strand transfer inhibitors and incident diabetes in people with HIV: a longitudinal cohort study.

OBJECTIVE: Integrase strand transfer inhibitors (INSTI) are associated with weight gain in people with HIV (PWH), but their impact on diabetes is unclear. We evaluated the association between switching from nonnucleoside reverse-transcriptase inhibitors (NNRTI) or protease inhibitors (PI) to INSTI and incident diabetes. DESIGN: Longitudinal cohort study. METHODS: We included PWH aged ≥18 years from the Johns Hopkins HIV Clinical Cohort (2007-2023) without history of diabetes who had used NNRTI or PI for ≥180 days. We followed participants up to 10 years from HIV primary care visits where they switched to INSTI or continued NNRTI or PI. We estimated the hazard of incident diabetes associated with switching to INSTI using weighted Cox regression with robust variance estimator. RESULTS: We included 2,075 PWH who attended 22,116 visits where they continued NNRTI or PI and 631 visits where they switched to INSTI. Switching to INSTI was associated with a weighted hazard ratio (wHR) of 1.11 (95% confidence interval [CI], 0.77-1.59) for incident diabetes. The association if no weight gain occurred during the first two years was not qualitatively different (wHR 1.22; 95% CI, 0.82-1.80). In a posthoc analysis, switching to INSTI conferred a significant wHR of 1.79 (95% CI, 1.13-2.84) for diabetes within the first two years but not after. CONCLUSIONS: Switching from NNRTI or PI to INSTI did not significantly increase overall diabetes incidence in PWH, although there may be elevated risk in the first two years. These findings can inform considerations when switching to INSTI-based regimens.

Cryoablation Utilizing the KODEX-EPD Mapping System Versus Conventional Cryoballoon Ablation in the Management of Patients With Atrial Fibrillation: A Literature Review and Meta-Analysis.

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia globally. AF is associated with different consequences, such as peripheral vascular embolism, stroke, dementia, heart failure, and death. Catheter ablation (CA) has become a reliable therapeutic option for symptomatic AF. Utilizing mapping systems in conducting cryoablation is supposed to improve pulmonary vein isolation (PVI) durability and overall treatment success rate. We performed a review of relevant articles. We formulated a search strategy as follows: (atrial fibrillation AND ("cryoballoon ablation" OR cryoablation) AND (KODEX-EPD AND KODEX OR mapping). Data were collected from Web of Science, PubMed, Cochrane Library, and SCOPUS databases. We assessed the efficacy, procedural characteristics, and safety of cryoablation using the KODEX-EPD mapping system versus conventional cryoablation. We demonstrated the superiority of cryoablation guided by the KODEX-EPD system as it was associated with a significantly lower recurrence rate after the procedure (RR = 0.61, P = 0.03). Furthermore, it allowed a significant reduction in the volume of contrast medium used during the procedure (MD = -20.46, P = 0.04) when compared to the conventional cryoablation. We found no significant difference between both procedures in terms of successful cryoballoon-based PVI (P = 1.00), procedural duration (P = 0.95), procedural complications (P = 0.607), fluoroscopic time (P = 0.36), and fluoroscopic dose (P = 0.16). The use of the novel KODEX-EPD mapping system in the cryoablation procedure was associated with a significant reduction of the volume of contrast medium use and the recurrence rate compared with the conventional cryoablation while preserving similar efficacy, safety profile, and procedure time.

Ulnocarpal Abutment Syndrome With Triquetrum Degeneration.

We present the case of a 47-year-old patient with a congenital positive ulnar variance and elucidate its effects on nearby structures in relation to ulnocarpal abutment syndrome (UAS). While magnetic resonance imaging (MRI) helped to identify soft tissue changes in the wrist, the use of an arthrogram, in this case, allowed for a more comprehensive and detailed analysis of the ligaments and soft tissues. Image findings included a complex degenerative tear of the disc of the triangular fibrocartilage (TFCC), a degenerated triquetrum, and partial tears of the scapholunate and lunotriquetral ligaments. Mild dorsal angulation of the lunate was noted, representing dorsal intercalated segmental instability (DISI), suggesting scapholunate ligament injury. Palmar classification was utilized to classify the extent of the TFCC injury as Type IIE. This case shines a light on the presentation of UAS in a patient that was not the usual demographic affected by this pathology, as well as their UAS affecting the triquetrum rather than the more commonly associated lunate.

Comparative Analysis of Slow Mohs Surgery in Melanoma and Mohs Micrographic Surgery in Squamous Cell Carcinoma and Basal Cell Carcinoma.

Skin cancer is one of the most common types of cancer worldwide, and it can affect people of all ages, races, and genders. Mohs micrographic surgery (MMS), a specialized type of skin cancer surgery, boasts the highest cure rates for various types of skin malignancies. Slow Mohs surgery (SMS) is a methodical and meticulous approach to MMS that involves careful and deliberate examination of tissue samples to ensure the complete removal of skin cancer while preserving as much healthy tissue as possible. Both SMS and MMS have been indicated to be effective treatment options for skin cancer, depending on the type and stage of cancer. This case-control study analysis compares the efficacy of SMS for melanoma with that of MMS for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). We analyzed data from the past two decades to assess recurrence rates and treatment-related complications. Our findings suggest that SMS for melanoma achieves comparable outcomes to MMS in SCC and BCC. Both approaches demonstrated similar cure rates and complication profiles. However, further prospective studies are necessary to solidify these findings and refine the specific role of SMS in melanoma therapy.

Efficacy of Laser Therapy in Comparison With Other Methods for the Treatment of Onychomycosis: A Systematic Review and Meta-Analysis.

Onychomycosis, a fungal infection of the nails, presents a significant challenge in clinical management due to its chronic nature and resistance to conventional therapies. This study aims to evaluate the efficacy of laser therapy in treating onychomycosis compared to traditional methods such as terbinafine. A systematic review and meta-analysis were conducted to analyze existing literature on the subject. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram illustrates the selection process of studies. Findings suggest that laser therapy demonstrates promising results in the treatment of onychomycosis, with comparable efficacy to terbinafine and fewer adverse effects. Further large-scale randomized controlled trials are warranted to validate these findings and establish laser therapy as a standard treatment option for onychomycosis.

Establishment of a Four-Cell In Vitro Blood-Brain Barrier Model With Human Primary Brain Cells.

The blood-brain barrier (BBB) constitutes a crucial protective anatomical layer with a microenvironment that tightly controls material transit. Constructing an in vitro BBB model to replicate in vivo features requires the sequential layering of constituent cell types. Maintaining heightened integrity in the observed tight junctions during both the establishment and post-experiment phases is crucial to the success of these models. We have developed an in vitro BBB model that replicates the cellular composition and spatial orientation of in vivo BBB observed in humans. The experiment includes comprehensive procedures and steps aimed at enhancing the integration of the four-cell model. Departing from conventional in vitro BBB models, our methodology eliminates the necessity for pre-coated plates to facilitate cell adhesion, thereby improving cell visualization throughout the procedure. An in-house coating strategy and a simple yet effective approach significantly reduce costs and provides superior imaging of cells and corresponding tight junction protein expression. Also, our BBB model includes all four primary cell types that are structural parts of the human BBB. With its innovative and user-friendly features, our in-house optimized in vitro four-cell-based BBB model showcases novel methodology and provides a promising experimental platform for drug screening processes. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Coating and culture system Basic Protocol 2: Cell seeding and Transwell insert handling Basic Protocol 3: Assessment of model functionality.

A Dwindling Matter: An Analysis of Medicare Reimbursement for Endocrine Surgery Procedures from 2000-23.

OBJECTIVE: To evaluate Medicare reimbursement trends for endocrine surgeries from 2000-23. BACKGROUND: As the population ages, demand for endocrine surgeries is expected to increase. Understanding reimbursement trends is essential to ensure the financial sustainability of endocrine surgery. METHODS: Data were extracted from Medicare Inpatient and Outpatient Hospital datasets, National Summary, and Physician Fee Look-up Files for nine common thyroid, parathyroid and adrenal surgeries. Data were adjusted for inflation. Descriptive statistics, compound annual growth rate (CAGR), and linear regression models were built to evaluate practice and reimbursement trends. RESULTS: From 2000-23, there was a 63.8% increase in endocrine surgery volume. However, inflation-adjusted average procedure reimbursements decreased by 43.2% from $1709 to $972 (CAGR -2.4%), which is the largest decrease for any surgical subspecialty reported in the published literature. At the current CAGR, the average estimated reimbursement is projected to decrease to $868 by 2030 (P<0.001). Average facility reimbursements for inpatient and outpatient hospitalizations increased. However, substantial practice pattern shifts in the study period led to decreased overall facility reimbursements, with a $17.9 million decrease in total inpatient reimbursements between 2016-21 that was only partially offset by a $3.2 million increase in outpatient hospital reimbursements. CONCLUSION: Medicare procedure reimbursements for endocrine surgeries have been outpaced by inflation, with large decreases since 2000. Concurrent changes in practice patterns have also resulted in markedly fewer inpatient stays leading to lower total facility reimbursements. Our data raise concern over the financial sustainability of the endocrine surgery field as the demand for endocrine surgery procedures increases.

Psychopharmacological interaction of alcohol and posttraumatic stress disorder: Effective action of naringin.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are prevalently co-occurring, important risk factors for a broad array of neuropsychiatric diseases. To date, how these two contrastive concomitant pairs increase the risk of neuropsychiatric states, notably exacerbating PTSD-related symptoms, remains unknown. Moreover, pharmacological interventions with agents that could reverse PTSD-AUD comorbidity, however, remained limited. Hence, we investigated the neuroprotective actions of naringin in mice comorbidly exposed to PTSD followed by repeated ethanol (EtOH)-induced AUD. Following a 7-day single-prolong-stress (SPS)-induced PTSD in mice, binge/heavy drinking, notably related to AUD, was induced in the PTSD mice with every-other-day ethanol (2 g/kg, p.o.) administration, followed by daily treatments with naringin (25 and 50 mg/kg) or fluoxetine (10 mg/kg), from days 8-21. PTSD-AUD-related behavioral changes, alcohol preference, hypothalamic-pituitary-adrenal (HPA)-axis dysfunction-induced neurochemical alterations, oxidative/nitrergic stress, and inflammation were examined in the prefrontal-cortex, striatum, and hippocampus. PTSD-AUD mice showed aggravated anxiety, spatial-cognitive, social impairments and EtOH intake, which were abated by naringin, similar to fluoxetine. Our assays on the HPA-axis showed exacerbated increased corticosterone release and adrenal hypertrophy, accompanied by marked dopamine and serotonin increase, with depleted glutamic acid decarboxylase enzyme in the three brain regions, which naringin, however, reversed, respectively. PTSD-AUD mice also showed increased TNF-α, IL-6, malondialdehyde and nitrite levels, with decreased antioxidant elements in the prefrontal-cortex, striatum, and hippocampus compared to SPS-EtOH-mice, mainly exacerbating catalase and glutathione decrease in the hippocampus relative SPS-mice. These findings suggest that AUD exacerbates PTSD pathologies in different brain regions, notably comprising neurochemical dysregulations, oxidative/nitrergic and cytokine-mediated inflammation, with HPA dysfunction, which were, however, revocable by naringin.

Enhanced Learning and Memory in Patients with CRB1 Retinopathy.

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in CRB1 retinopathy individuals with subjects with other retinopathies and the normal population. METHODS: Neuropsychological tests of cognitive function were used to test individuals with CRB1 and non-CRB1 retinopathies and compare results with a standardised normative dataset. RESULTS: CRB1 retinopathy subjects significantly outperformed those with non-CRB1 retinopathy in list learning tasks of immediate (p = 0.001) and delayed memory (p = 0.007), tests of semantic verbal fluency (p = 0.017), verbal IQ digit span subtest (p = 0.037), and estimation test of higher execution function (p = 0.020) but not in the remaining tests of cognitive function (p > 0.05). CRB1 retinopathy subjects scored significantly higher than the normal population in all areas of memory testing (p < 0.05) and overall verbal IQ tests (p = 0.0012). Non-CRB1 retinopathy subjects scored significantly higher than the normal population in story recall, verbal fluency, and overall verbal IQ tests (p = 0.0016). CONCLUSIONS: Subjects with CRB1 retinopathy may have enhanced cognitive function in areas of memory and learning. Further work is required to understand the role of CRB1 in cognition.

The feasibility, appropriateness, and usability of mobile neuro clinics in addressing the neurosurgical and neurological demand in Uganda.

INTRODUCTION: Uganda has a high demand for neurosurgical and neurological care. 78% of the over 50 million population reside in rural and remote communities where access to neurosurgical and neurological services is lacking. This study aimed to determine the feasibility, appropriateness, and usability of mobile neuro clinics (MNCs) in providing neurological care to rural and remote Ugandan populations. METHODS: Neurosurgery, neurology, and mobile health clinic providers participated in an education and interview session to assess the feasibility, appropriateness, and usability of the MNC intervention. A qualitative analysis of the interview responses using the constructs in the updated Consolidated Framework for Implementation Research was performed. Providers' opinions were weighted using average sentiment scores on a novel sentiment-weighted scale adapted from the CFIR. A stakeholder analysis was also performed to assess the power and interest of the actors described by the participants. RESULTS: Twenty-one healthcare providers completed the study. Participants discussed the potential benefits and concerns of MNCs as well as potential barriers and critical incidents that could jeopardize the intervention. Of the five CFIR domains evaluated, variables in the implementation process domain showed the highest average sentiment scores, followed by the implementation climate constructs, inner setting, innovation, and outer setting domains. Furthermore, many interested stakeholders were identified with diverse roles and responsibilities for implementing MNCs. These findings demonstrate that MNC innovation is feasible, appropriate, and usable. CONCLUSION: The findings of this study support the feasibility, appropriateness, and usability of MNCs in Uganda. However, integration of this innovation requires careful planning and stakeholder engagement at all levels to ensure the best possible outcomes.

Large-scale neurophysiology and single-cell profiling in human neuroscience.

Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.

The tidyomics ecosystem: Enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis, and integration. Addressing these challenges, Bioconductor1 provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming2 offers a revolutionary standard for data organisation and manipulation. Here, we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning, and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analysing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas3, spanning six data frameworks and ten analysis tools.

Bellybutton: accessible and customizable deep-learning image segmentation.

The conversion of raw images into quantifiable data can be a major hurdle and time-sink in experimental research, and typically involves identifying region(s) of interest, a process known as segmentation. Machine learning tools for image segmentation are often specific to a set of tasks, such as tracking cells, or require substantial compute or coding knowledge to train and use. Here we introduce an easy-to-use (no coding required), image segmentation method, using a 15-layer convolutional neural network that can be trained on a laptop: Bellybutton. The algorithm trains on user-provided segmentation of example images, but, as we show, just one or even a sub-selection of one training image can be sufficient in some cases. We detail the machine learning method and give three use cases where Bellybutton correctly segments images despite substantial lighting, shape, size, focus, and/or structure variation across the regions(s) of interest. Instructions for easy download and use, with further details and the datasets used in this paper are available at pypi.org/project/Bellybuttonseg .

Prebiotic galactooligosaccharide improves piglet growth performance and intestinal health associated with alterations of the hindgut microbiota during the peri-weaning period.

BACKGROUND: Weaning stress reduces growth performance and health of young pigs due in part to an abrupt change in diets from highly digestible milk to fibrous plant-based feedstuffs. This study investigated whether dietary galactooligosaccharide (GOS), supplemented both pre- and post-weaning, could improve growth performance and intestinal health via alterations in the hindgut microbial community. METHODS: Using a 3 × 2 factorial design, during farrowing 288 piglets from 24 litters received either no creep feed (FC), creep without GOS (FG-) or creep with 5% GOS (FG+) followed by a phase 1 nursery diet without (NG-) or with 3.8% GOS (NG+). Pigs were sampled pre- (D22) and post-weaning (D31) to assess intestinal measures. RESULTS: Creep fed pigs grew 19% faster than controls (P < 0.01) prior to weaning, and by the end of the nursery phase (D58), pigs fed GOS pre-farrowing (FG+) were 1.85 kg heavier than controls (P < 0.05). Furthermore, pigs fed GOS in phase 1 of the nursery grew 34% faster (P < 0.04), with greater feed intake and efficiency. Cecal microbial communities clustered distinctly in pre- vs. post-weaned pigs, based on principal coordinate analysis (P < 0.01). No effects of GOS were detected pre-weaning, but gruel creep feeding increased Chao1 α-diversity and altered several genera in the cecal microbiota (P < 0.05). Post-weaning, GOS supplementation increased some genera such as Fusicatenibacter and Collinsella, whereas others decreased such as Campylobacter and Frisingicoccus (P < 0.05). Changes were accompanied by higher molar proportions of butyrate in the cecum of GOS-fed pigs (P < 0.05). CONCLUSIONS: Gruel creep feeding effectively improves suckling pig growth regardless of GOS treatment. When supplemented post-weaning, prebiotic GOS improves piglet growth performance associated with changes in hindgut microbial composition.