Browsing by Subject "Gut-brain axis"

Now showing 1 - 4 of 4
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    Gut-Brain cross talk: The pathogenesis of neurodevelopmental impairment in necrotizing enterocolitis
    (Frontiers Media, 2023-02-15) Manohar, Krishna; Mesfin, Fikir M.; Liu, Jianyun; Shelley, W. Christopher; Brokaw, John P.; Markel, Troy A.; Surgery, School of Medicine
    Necrotizing enterocolitis (NEC) is a devastating condition of multi-factorial origin that affects the intestine of premature infants and results in high morbidity and mortality. Infants that survive contend with several long-term sequelae including neurodevelopmental impairment (NDI)-which encompasses cognitive and psychosocial deficits as well as motor, vision, and hearing impairment. Alterations in the gut-brain axis (GBA) homeostasis have been implicated in the pathogenesis of NEC and the development of NDI. The crosstalk along the GBA suggests that microbial dysbiosis and subsequent bowel injury can initiate systemic inflammation which is followed by pathogenic signaling cascades with multiple pathways that ultimately lead to the brain. These signals reach the brain and activate an inflammatory cascade in the brain resulting in white matter injury, impaired myelination, delayed head growth, and eventual downstream NDI. The purpose of this review is to summarize the NDI seen in NEC, discuss what is known about the GBA, explore the relationship between the GBA and perinatal brain injury in the setting of NEC, and finally, highlight the existing research into possible therapies to help prevent these deleterious outcomes.
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    Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction
    (Sage, 2022-05-22) Nwafor, Divine C.; Brichacek, Allison L.; Foster, Chase H.; Lucke-Wold, Brandon P.; Ali, Ahsan; Colantonio, Mark A.; Brown, Candice M.; Qaiser, Rabia; Neurological Surgery, School of Medicine
    Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain’s vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.
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    Prevalence of small intestinal bacterial overgrowth in patients with gastroparesis: a systematic review and meta-analysis
    (Research Institute for Gastroenterology and Liver Diseases, 2023) Beas, Renato; Riva-Moscoso, Adrian; Montalvan-Sanchez, Eleazar; Príncipe-Meneses, Fortunato S.; Aljaras, Rawan; Ramirez, Mirian; Izquierdo-Veraza, Diego; Calderon, Gerardo; Medicine, School of Medicine
    Aim: We performed a systematic review and meta-analysis to identify the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with gastroparesis. Background: Several studies have suggested an association between SIBO and gastroparesis, which is characterized by delayed gastric emptying in the absence of mechanical obstruction. Methods: A comprehensive search was performed using MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) through January, 2022 for randomized controlled trials and observational studies reporting the prevalence of SIBO in gastroparesis. Pooled prevalence was estimated using a random effects model. Heterogeneity was assessed by using the inconsistency index (I2). Results: Among the 976 articles identified, 43 studies were selected for full text review. Six studies, with 385 patients, were deemed eligible for inclusion, with a perfect agreement between investigators (kappa=1.0). Overall, 379 patients were diagnosed with gastroparesis by gastric emptying scintigraphy and six were diagnosed with a wireless motility capsule. The pooled prevalence of SIBO was 41% (95% confidence interval 0.23-0.58). SIBO was diagnosed using jejunal aspirate cultures (N=15, 8.4%), lactulose breath test (N=80, 44.7%), glucose breath test (N=30, 16.8%), D-xylose breath test (N=52, 29.1%), and hydrogen breath test (N=2, 1.1%). Heterogeneity was significant and noted to be high at 91%. Only one study reported SIBO diagnosis in controls, therefore no pooled odds ratio was calculated. Conclusion: SIBO was present in almost half of the patients with gastroparesis. Future studies should examine and identify the association between SIBO and gastroparesis.
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    Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation
    (Elsevier, 2023-06-05) Churchward, Matthew A.; Michaud, Emily R.; Mullish, Benjamin H.; Blanco, Jesús Miguens; Garcia Perez, Isabel; Marchesi, Julian R.; Xu, Huiping; Kao, Dina; Todd, Kathryn G.; Biostatistics and Health Data Science, School of Medicine
    The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association are poorly understood. Short-chain fatty acids and carboxylic acids (SCCA) produced by the intestinal microbiota cross the blood brain barrier and have been proposed to contribute to gut-brain communication. We hypothesized that changes in serum SCCA measured before and after successful FMT for rCDI influences the inflammatory response of microglia, the resident immune cells of the central nervous system. Serum SCCA were quantified using gas chromatography-mass spectroscopy from 38 patients who participated in a randomized trial comparing oral capsule-vs colonoscopy-delivered FMT for rCDI, and quality of life was assessed by SF-36 at baseline, 4, and 12 weeks after FMT treatment. Successful FMT was associated with improvements in mental and physical health, as well as significant changes in a number of circulating SCCA, including increased butyrate, 2-methylbutyrate, valerate, and isovalerate, and decreased 2-hydroxybutyrate. Primary cultured microglia were treated with SCCA and the response to a pro-inflammatory stimulus was measured. Treatment with a combination of SCCA based on the post-FMT serum profile, but not single SCCA species, resulted in significantly reduced inflammatory response including reduced cytokine release, reduced nitric oxide release, and accumulation of intracellular lipid droplets. This suggests that both levels and diversity of SCCA may be an important contributor to gut-brain communication.