Digital Commons Network^™

Liver Injury In A Preclinical Model Of Short Bowel Syndrome Is Associated With Impaired Autophagy, Daniel M Alligood, Alex Park, Kerry Swanson, Naima Pyarali, Evan Mayse, David M Alvarado, Xiuli Liu, Jae-Sung Kim, Nicholas O Davidson, Deborah C Rubin, Jun Guo, Brad W Warner

2020-Current year OA Pubs

Critical for cellular maintenance and repair, autophagy recycles damaged or redundant cellular components. Dysregulated autophagy is associated with progressive cellular injury in various liver pathologies. However, the role of autophagy in intestinal failure-associated liver disease has not previously been investigated. Using a preclinical murine model of short bowel syndrome, we explored the role of autophagy impairment at early and late time points. Regardless of sex, small bowel resected (SBR) mice demonstrated significant liver injury compared to sham controls, exhibiting elevated serum transaminases, altered liver histology, and increased mRNA expression of endoplasmic reticulum stress marker (Ddit3) and oxidative stress marker (Nqo1). …

Insm1 Governs A Neuronal Progenitor State That Drives Glioblastoma In A Human Stem Cell Model, Patrick A Desouza, Matthew Ishahak, Xuan Qu, Colin Mccornack, Devi Annamalai, Diane D Mao, Rajanikanth Vangipurapu, Yiwei Fu, Alexandre T Vessoni, Ryan T Cleary, Rowland H Han, Punn Augsornworawat, Timothy Woodiwiss, Darby Agovino, Braxton Sizemore, Jessica Kline, Maryam Borhani-Haghighi, Hao Chen, Sangami Pugazenthi, Hiroko Yano, Ting Wang, Luis F Z Batista, Jeffrey R Millman, Albert H Kim

2020-Current year OA Pubs

Glioblastoma is a lethal brain cancer marked by functional plasticity driven by tumor cell-intrinsic mutations and their interplay with developmental programs. To investigate how canonical glioblastoma mutations promote functional plasticity, we have developed an isogenic human neural stem cell (NSC) model of glioblastoma by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increases TERT expression during serial mutagenesis, but only triple mutant NSCs reliably form lethal brain tumors in vivo that recapitulate glioblastoma. Tumor cell evolution triggers stress-related metabolic changes and transitions toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed …

Resolving The Mysteries Of Brain Clearance And Immune Surveillance, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Recent advances are transforming our understanding of brain fluid dynamics, highlighting cerebrospinal fluid (CSF) flow as a key process in brain waste clearance. While debates persist regarding its anatomical pathways and regulatory mechanisms, certain core principles have become widely accepted. CSF influx occurs primarily along periarterial spaces, solute clearance follows multiple routes, and glymphatic and meningeal lymphatic systems are functionally connected. Brain clearance is influenced by vascular pulsation, neural activity, and sleep. Immune cells at brain-border niches both monitor solute efflux and modulate flow, linking brain clearance to neuroimmune interactions. A deeper understanding of brain clearance could unlock new therapeutic …

Using Gnotobiotic Mice To Decipher Effects Of Gut Microbiome Repair In Undernourished Children On Tuft And Goblet Cell Function, Yi Wang, Hao-Wei Chang, Jiye Cheng, Daniel M Webber, Hannah M Lynn, Matthew C Hibberd, Clara Kao, Ishita Mostafa, Tahmeed Ahmed, Michael J Barratt, Jeffrey I Gordon

2020-Current year OA Pubs

Studies have implicated perturbations in the postnatal development of the gut microbiome as a contributing factor to childhood undernutrition. Compared to a standard ready-to-use supplementary food, a microbiome-directed complementary food (MDCF-2) designed to repair these perturbations produced superior improvements in ponderal and linear growth in clinical trials of Bangladeshi children with moderate acute malnutrition. Here, "reverse translation" experiments are performed where intact fecal microbiomes collected from trial participants before and at the end of treatment are introduced into female gnotobiotic mice just after delivery of their pups. Pups received diets designed to resemble those consumed by children in the trials …

Molecular Response To The Non-Lytic Peptide Bac7 (1-35) Triggers Disruption Of Klebsiella Pneumoniae Biofilm, Robert L Beckman I V, Berta Martinez, Flor Z. Santiago, Gabriela N. Echeverria, Bruno V. Pinheiro, Marcelo D. T. Torres, Logan Suits, Shantal Garcia, Paeton L. Wantuch, Cesar De La Fuente-Nunez, Prahathees Eswara, David A. Rosen, Renee M. Fleeman

2020-Current year OA Pubs

Klebsiella pneumoniae is becoming increasingly difficult to treat as multidrug-resistant (MDR) strains become more prevalent. The formation of biofilm heightens this threat by embedding bacterial cells in a polysaccharide-rich matrix that limits antibiotic penetration. Here we dissect the anti-biofilm bovine host-defense cathelicidin peptide fragment bac7 (1-35), exploring its anti-biofilm mechanism, evaluating its ability to curb colonization of the vital organs by hypervirulent K. pneumoniae, and testing its breadth of activity against diverse clinical isolates. Transcriptomic profiling revealed that bac7 (1-35) simultaneously compromises the bacterial membrane and inhibits ribosomal function, a dual assault that precipitates rapid biofilm collapse and blocks bacterial …

Improved Accuracy For Myocardial Blood Flow Mapping With Deep Learning-Enabled Cmr Arterial Spin Labeling (Deepmasl): Validation By Microsphere In Vivo, Ran Li, Caleb Berberet, Qi Huang, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Current myocardial arterial spin labeling (ASL) methods are sensitive to noise (background and physiology), which limits the accuracy of myocardial blood flow (MBF) measurement. In this study, we demonstrated a new deep learning-enabled myocardial ASL approach (DeepMASL) and evaluated its accuracy to quantify MBF in a canine model of coronary arterial disease in vivo. The reference method was invasive microsphere measurements.

METHODS: Eighteen mongrel dogs were divided into two groups: healthy (n = 9) and coronary stenosis (n = 9). The latter was induced in an open-chest model with 3 types of stenosis: 50% (n= 3), 70% (n = …

Muc15 Ectodomain Architecture Regulates Integrin Clustering To Control Cancer Metastasis, Simei Zhang, Guy M Genin, Et Al.

2020-Current year OA Pubs

Cancer metastasis is governed by physical cues at the cell-matrix interface, with matrix stiffness, ligand density, and topography established as key determinants. Here, a fourth critical factor in cancer metastasis, the architecture of the cell-surface glycocalyx is identified. Using MUC15 as a representative small glycoprotein, mathematical modeling and domain truncation experiments are combined to show that glycoprotein size distribution governs integrin adhesion states and metastatic outcomes. MUC15 localizes to focal adhesions and interact with integrins, while larger glycoproteins such as MUC1 are sterically excluded. These physical effects, rather than intracellular signaling, dictate adhesion state transitions: removing MUC15's ectodomain eliminated its …

Renal Replacement Therapy In Lupus Nephritis-Related End-Stage Kidney Disease: A Systematic Review And Meta-Analysis, Hassan Kawtharany, Jessica N Williams, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To assess the impact of renal replacement therapy in people with lupus nephritis (LN)-associated end-stage kidney disease (ESKD) and support the development of the 2024 American College of Rheumatology LN treatment guidelines.

METHODS: We conducted a systematic literature review and meta-analysis to address three Population, Intervention, Comparison, and Outcome (PICO) questions related to renal replacement therapy for ESKD due to LN, including comparisons of kidney transplant versus dialysis, hemodialysis versus peritoneal dialysis, and preemptive kidney transplant versus no preemptive kidney transplant. Outcomes of interest included mortality, cardiovascular (CV) events, infections, lupus flares, disease-related damage, graft failure, and quality of …

Adverse Experiences, Protective Factors, And Obesity In Latinx And Hispanic Youths, Victoria Goldman, Sevan Esaian, Miguel Ángel Rivas Fernández, Jonatan Ottino Gonzalez, Nicole Karcher, Jeffrey I Gold, Alaina P Vidmar, Shana Adise

2020-Current year OA Pubs

IMPORTANCE: Pediatric obesity rates are rising, and adverse childhood experiences (ACEs) may contribute by promoting stress-induced weight gain. Few studies have examined the association of ACEs with body mass index (BMI) and youth-reported protective factors, particularly among Latinx and Hispanic youths, who face higher rates of ACEs and obesity.

OBJECTIVE: To evaluate the association of ACEs with BMI in a population-based cohort and determine whether youth-reported protective factors (eg, self-coping skills, caregiver or friend support, or overall support) moderate this association, with a focus on Latinx and Hispanic youths.

DESIGN, SETTING, AND PARTICIPANTS: This large, cross-sectional study of youths aged …

Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.

OBJECTIVES: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the 2 species.

METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc

RESULTS: Diet-induced obesity reduced survival in …

In Situ Structural Mechanism Of Epothilone-B-Induced Cns Axon Regeneration, Satish Bodakuntla, Kenichiro Taira, Yurika Yamada, Pelayo Alvarez-Brecht, A King Cada, Nirakar Basnet, Rui Zhang, Antonio Martinez-Sanchez, Christian Biertümpfel, Naoko Mizuno

2020-Current year OA Pubs

Axons in the adult central nervous system (CNS) do not regenerate following injury, in contrast to neurons in the peripheral nervous system and neuronal growth during embryonic development. The molecular mechanisms that prevent regeneration of neurons in the CNS remain largely unknown

Early Life Infection With Cryptosporidium Parvum Induces Inflammatory Responses To Dietary Antigens, Iti Saraav, Wanyi Huang, Jisun Jung, Rui Xu, Yong Fu, Keely Mcdonald, Lawrence A Schriefer, Rachel Rodgers, Megan T Baldridge, Rodney D Newberry, Chyi-Song Hsieh, L David Sibley

2020-Current year OA Pubs

To examine the effect of early-life infection with

Pan-Cancer Single Cell Transcriptomic Clustering Reveals Heterogeneous Cd8+ Exhausted T Cell Populations With Different Immune Checkpoint Inhibitor Responses, Rui Mu, Rasha Barakat, David H Gutmann

2020-Current year OA Pubs

In most cancers, T lymphocytes comprise an essential cellular component of the non-neoplastic microenvironment, where they have the capacity to both suppress and support tumor growth. One specialized T lymphocyte population is the CD8

Lymphoid Gene Expression Supports Neuroprotective Microglia Function, Pinar Ayata, Maud Gratuze, Jason D Ulrich, David M Holtzman, Et Al.

2020-Current year OA Pubs

Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer's disease (AD)

Age-Dependent Zap70 Expression In Thymocytes Regulates Selection Of The Neonatal Regulatory T Cell Repertoire, Brian D Stadinski, Robert A Campbell, Et Al.

2020-Current year OA Pubs

The Foxp3⁺ regulatory T (T

Semi-Annual And Annual Mass Drug Administration Of Diethylcarbamazine And Albendazole Are Equally Effective Regimens For Eliminating Lymphatic Filariasis In Papua New Guinea, Michael C. Payne, Nelly Sanuku, Brooke E. Mancuso, Yao-Chieh Cheng, Gary J. Weil, Peter U. Fischer, Moses Laman, Leanne J. Robinson, Daniel J. Tisch, Christopher L King

2020-Current year OA Pubs

Annual mass drug administration (MDA) is currently recommended for the local elimination of lymphatic filariasis (LF). Modeling studies of LF transmission suggest that conducting MDA twice a year could accelerate LF elimination. To test this idea, we compared the effects of 3 rounds of yearly MDA and 5 rounds of semiannual MDA using diethylcarbamazine with albendazole on LF infection measures in Papua New Guinea (PNG) across 2 treatment areas with high LF prevalence. From 2013 to 2018, we conducted 4 annual community surveys at 4 sentinel sites in each treatment area. We sampled 2,854 people at the start and 2,746, …

Development Of Intestinal Tissue-Resident T Cells In Early-Life Mice Before And After Weaning, Catherine Montenegro, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco

2020-Current year OA Pubs

Intestinal tissue-resident T cells have been poorly characterized during early-life. Here, we phenotypically characterized tissue-resident (intravascular staining negative) CD4

Structure Of An Lgr Dimer, An Evolutionary Predecessor Of Glycoprotein Hormone Receptors, Zhen Gong, Shuobing Chen, Ziao Fu, Brian Kloss, Chi Wang, Jonathan Kim, Oliver B Clarke, Qing R Fan, Wayne A Hendrickson

2020-Current year OA Pubs

Glycoprotein hormones (GpHs) produced in the human pituitary act through receptors (GpHRs) in the gonads to support reproduction and in the thyroid for metabolism. GpHs are heterodimeric cystine-knot proteins; their receptors bind cognate hormones at an extracellular domain and signal through a transmembrane domain to heterotrimeric G proteins. GpHs and GpHRs have co-evolved from invertebrate counterparts. Structures of the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers. Here we characterize the homologous receptor from Caenorhabditis elegans. Its biochemical properties are notably similar to those of the thyroid stimulating …

Maternal Obesogenic Diet Exposure Regulates The Offspring Gut Liver Axis And Fibroinflammatory Liver Disease, Naresh Naik Ramavath, Oğuz Özler, Holly Hinrichs, Francisco R Victorino, Vung Lian, Monica Young, Tarin M Bigley, Michael D Thompson

2020-Current year OA Pubs

Maternal obesogenic diet exposure (MODE) promotes fibroinflammatory liver disease in offspring via vertical transfer of an altered microbiome. The mechanism for how an altered offspring microbiome increases susceptibility to liver disease is not clear. A critical early life event termed the 'weaning reaction' is dependent on the early microbiome and when altered, results in worse pathologic inflammation. MODE attenuates the weaning reaction promoting worse liver disease in mice in an early microbiome-dependent manner. Using our MODE model and cross-fostering approaches we assessed the effect of MODE on neonatal gut-liver axis development. MODE shifts the bile acid (BA) profile, expression of …

Mitochondrial Iron Transport Via Mfrn1 Is Required For Erythroid Cell Cycle Progression, Mark Perfetto, Aidan Danoff, Muhammad Ishfaq, Heidi Monroe, Aiden Mohideen, Meilin Chen, Jesus Tejero, Amber N Stratman, Satoshi Okawa, Yvette Y Yien

2020-Current year OA Pubs

Iron metabolism drives key erythropoietic processes, including hemoglobinization, survival, and proliferation. Here, we developed in vivo methods to interrogate how iron regulates erythropoiesis and report that mitochondrial iron transport via mitoferrin-1 (MFRN1) is essential for erythroid cell cycle progression. mfrn1 embryos had severely decreased erythroid cell number caused by cell cycle arrest at G2/M. They had enlarged nuclei, suggesting a mitotic defect. Iron supplementation rescued the cell cycle defect, implicating mitochondrial iron deficiency as its cause. In contrast, fpn1 mutants, anemic from systemic iron deficiency, had less severe decreases in erythroid mitochondrial iron than mfrn1 mutants and no proliferative defects. …

Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain

2020-Current year OA Pubs

Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in …

Modulation Of Dorsal Hippocampal Sk2 Channels Regulates Morphine-Enhanced Neuronal Oscillations And Morphine-Induced Contextual Memory Encoding And Retrieval, Khairunisa Mohamad Ibrahim, Dominika J Burek, Azra Zec, Olayinka Idowu, Will W Post, Alice Zheng, Basma Daham, Justin D Meyer, Sidney Williams, Nicolas Massaly, Jose A Morón

2020-Current year OA Pubs

Persistent maladaptive drug-context associations are a key component of relapse vulnerability and pose a major obstacle in treating opioid use disorder. Although the dorsal hippocampus (dHPC) is critical for contextual memory formation, the synaptic mechanisms by which opioids alter hippocampal circuits to sustain these associations remain unclear. We previously found that repeated context-paired morphine exposure impairs dHPC long-term potentiation (LTP) through enhanced activity of small-conductance calcium-activated potassium (SK2) channels. Here, we investigated the role of SK2 channels in morphine-context associative learning and memory by combining in vivo electrophysiology, molecular analyses, and behavioral pharmacology with the morphine-conditioned place preference (MorCPP) paradigm …

Depth-Variant Deconvolution Applied To Widefield Microscopy For Rapid Large-Volume Tissue Imaging, Daniel D Lee, Kevin A Telfer, Mark A J Koenis, Yim K Lee, Kevin W Namink, Brian T Saunders, Heyun Lee, Hailey Kelley, Heather S Ruiz, Joseph P Gaut, Gwendalyn J Randolph, Bernd H Zinselmeyer

2020-Current year OA Pubs

Innovations in 3D tissue imaging have revolutionized research, but limitations stemming from lengthy protocols and equipment accessibility persist. Widefield microscopy is fast and accessible but often excluded from 3D imaging workflows due to its lack of optical sectioning. Here we combine tissue clearing with a commercial depth-variant deconvolution approach that we optimized for large-volume widefield imaging. By implementing prefiltering with z-brick splitting, we achieve subnuclear axial resolution in tissues to a depth of 500 µm in multi-tile scan images. We illustrate the utility of this method in a model of ileitis and to gain a 3D perspective in thick brain …

Ptbp1 Variants Displaying Altered Nucleocytoplasmic Distribution Are Responsible For A Neurodevelopmental Disorder With Skeletal Dysplasia, Aymeric Masson, Catherine Gooch, Et Al.

2020-Current year OA Pubs

Polypyrimidine tract-binding protein 1 (PTBP1) is a heterogeneous nuclear ribonucleoprotein primarily known for its alternative splicing activity. It shuttles between the nucleus and cytoplasm via partially overlapping N-terminal nuclear localization (NLS) and export (NES) signals. Despite its fundamental role in cell growth and differentiation, its involvement in human disease remains poorly understood. We identified 27 individuals from 25 families harboring de novo or inherited pathogenic variants - predominantly start-loss (89%) and, to a lesser extent, missense (11%) - affecting NES/NLS motifs. Affected individuals presented with a syndromic neurodevelopmental disorder and variable skeletal dysplasia with disproportionate short stature with short limbs. …

Generation And Characterization Of A Knockout Mouse Of An Enhancer Of Ebf3, Emily Cordova Hurtado, Janine M Wotton, Alexander Gulka, Crystal Burke, Jeffrey K Ng, Ibrahim Bah, Juana Manuel, Hillary Heins, Stephen A Murray, David U Gorkin, Jacqueline K White, Kevin A Peterson, Tychele N Turner

2020-Current year OA Pubs

Genomic studies of neurodevelopmental disorders (NDDs) have identified several relevant genomic variants. EBF3 is a gene with an excess of protein-coding de novo variants and underlies Hypotonia, Ataxia, and Delayed Development Syndrome. We previously identified noncoding de novo variants in an enhancer of EBF3 and further found enrichment of deletions of this enhancer in NDDs. In this study, we generated a novel mouse line that deletes the highly conserved, orthologous mouse region within the Rr169617 regulatory region, and characterized the molecular and phenotypic aspects of this mouse model. We found a deviation from Mendelian expectation (P=0.02) with significant depletion of …

Mta-Cooperative Prmt5 Inhibitors Are Efficacious In Mtap-Deleted Malignant Peripheral Nerve Sheath Tumor Models, Xiaochun Zhang, Dana C Borcherding, Yang Lyu, Guangfeng Wang, Kevin He, Gorkem Oztosun, Ishita Sachdeva, Liuzhan Yang, Kuangying Yang, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with poor prognosis. The enzyme methylthioadenosine phosphorylase (MTAP) is lost in ∼25% to 50% of MPNSTs, which is associated with loss of the tumor suppressor gene CDKN2A. Inhibition of PRMT5 was found to be synthetically lethal in cells with MTAP loss due to accumulation of the substrate methylthioadenosine (MTA), an endogenous PRMT5 inhibitor. TNG908 and TNG462 are clinical-stage MTA-cooperative PRMT5 inhibitors that demonstrate selectivity for MTAP-deleted (null) cells over MTAP-proficient [wild-type (WT)] cells. Both compounds drive durable tumor regressions in various cancer xenograft models with MTAP loss.

EXPERIMENTAL DESIGN: …

Lair1 Prevents Excess Inflammatory Tissue Damage In Staphylococcus Aureus Skin Infection And Cutaneous T-Cell Lymphoma, Hannah K. Dorando, Evan C. Mutic, Kelly L. Tomaszewski, Yulia Korshunova, Ling Tian, Mellisa K. Stefanov, Chaz C. Quinn, Deborah J. Veis, Juliane Bubeck Wardenburg, Amy C. Musiek, Neha Mehta-Shah, Jacqueline E. Payton

2020-Current year OA Pubs

Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the underlying mechanisms remain unclear. We have previously identified high levels of LAIR2, a decoy protein for the inhibitory receptor LAIR1, in advanced CTCL. Mice lack a LAIR2 homolog, so we used Lair1 knock-out (KO) mice to model LAIR2 overexpression. In a model of S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT despite similar bacterial burdens. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile …

Targeting Tomm40 And Tomm22 To Rescue Statin-Impaired Mitochondrial Function, Dynamics, And Mitophagy In Skeletal Myotubes, Neil V Yang, Sean Rogers, Rachel Guerra, Justin Y Chao, David J Pagliarini, Elizabeth Theusch, Ronald M Krauss

2020-Current year OA Pubs

Statins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well-tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated in the development of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates the transcription of

Host Cysteine Proteases Promote The Severity Of Catheter-Associated Urinary Tract Infection And Kidney Fibrosis, Wei Xu, Jian Chen, Lisa K Mclellan, Ana L Flores-Mireles, David A Hunstad, Michael G Caparon

2020-Current year OA Pubs

UNLABELLED: The bacterium

IMPORTANCE: Catheter-associated urinary tract infections (CAUTIs) are the most prevalent healthcare-associated infection globally, with

The Gut Microbiome As A Modulator Of Traumatic Brain Injury Pathology And Symptoms, Cole Vonder Haar, Marta Celorrio, Kris M Martens, Stuart H Friess, Sonia Villapol, Randal J Urban, Richard Pyles, Richelle Mychasiuk, Dennis Simon, Amanda Dave

2020-Current year OA Pubs

Traumatic brain injuries (TBIs) affect millions annually, leading to devastating neurobehavioral consequences and increasing risk for neurodegenerative and psychiatric diseases. However, therapies are lacking. Starting in 2018, dysbiosis of the gut microbiome was identified as an acute, and potentially chronic, pathology originating from TBI. Recent studies established that the microbiome contributes to the evolution of TBI pathology and functional impairments. The gut microbiome is the collection of microorganisms that inhabit the stomach through colon and is indicated as a contributor to myriad neurological and psychiatric conditions. This makes it an intriguing target to understand in the context of TBI. Thus, …