The longitudinal biochemical profiling of TBI in a drop weight model of TBI DOI Creative Commons
Ali Yilmaz, Sigal Liraz‐Zaltsman, Esther Shohami

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 14, 2023

Abstract Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide, particularly among individuals under the age 45. It complex, heterogeneous disease with multifaceted pathophysiology that remains to be elucidated. Metabolomics has potential identify metabolic pathways unique biochemical profiles associated TBI. Herein, we employed longitudinal metabolomics approach study TBI in weight drop mouse model reveal changes pathogenesis, severity, secondary injury. Using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy, biochemically profiled post-mortem from mice suffered mild (N = 25; 13 male 12 female), severe 24; 11 female) sham controls 16; 5 at baseline, day 7 following NMR-based metabolomics, combination bioinformatic analyses, highlights few significant metabolites severity perturbed metabolism related We report concentrations taurine , creatinine adenine dimethylamine histidine N-Acetyl aspartate glucose 1-phosphate are all severity. Longitudinal observation tissue revealed lead distinct profile changes. A multi-class was able classify as well time after estimated 86% accuracy. Further, identified high degree correlation between respective hemisphere (r > 0.84, p < 0.05, Pearson correlation). This underlying While comprehensive, future studies should investigate whether: (a) highlighted here recapitulated sufferers (b) if panel biomarkers also effective less invasively harvested biomatrices, for objective rapid identification prognosis.

Language: Английский

Small molecule metabolites: discovery of biomarkers and therapeutic targets DOI Creative Commons
Shi Qiu, Ying Cai, Hong Yao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

Citations

382
The metabolites of lactic acid bacteria: classification, biosynthesis and modulation of gut microbiota DOI Creative Commons

Huang Tang,

Wanqiu Huang,

Yu‐Feng Yao

et al.

Microbial Cell, Journal Year: 2023, Volume and Issue: 10(3), P. 49 - 62

Published: Feb. 24, 2023

Lactic acid bacteria (LAB) are ubiquitous microorganisms that can colonize the intestine and participate in physiological metabolism of host. LAB produce a variety metabolites, including organic acids, bacteriocin, amino exopolysaccharides vitamins. These metabolites basis function have profound impact on host health. The is colonized by large number gut with high species diversity. Metabolites keep balance stability microbiota through aiding maintenance intestinal epithelial barrier, resisting to pathogens regulating immune responses, which further influence nutrition, behavior In this review, we summarize their intestine. We also discuss underlying regulatory mechanisms emphasize link between human from perspective health promotion.

Language: Английский

Citations

59
The contribution of age-related changes in the gut-brain axis to neurological disorders DOI Creative Commons
Romeesa Khan, Claudia M. Di Gesù, June‐Young Lee

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 18, 2024

Trillions of microbes live symbiotically in the host, specifically mucosal tissues such as gut. Recent advances metagenomics and metabolomics have revealed that gut microbiota plays a critical role regulation host immunity metabolism, communicating through bidirectional interactions microbiota-gut-brain axis (MGBA). The regulates both systemic contributes to neurodevelopment behaviors host. With aging, composition changes, emerging studies linked these shifts microbial populations age-related neurological diseases (NDs). Preclinical demonstrated microbiota-targeted therapies can improve behavioral outcomes by modulating microbial, metabolomic, immunological profiles. In this review, we discuss pathways brain-to-gut or gut-to-brain signaling summarize metabolites across lifespan disease. We highlight recent investigating 1) changes with aging; 2) how aging maternal microbiome affect offspring health; 3) contribution chronic (e.g., Parkinson's disease, Alzheimer's disease cerebral amyloidosis), acute brain injury, including ischemic stroke traumatic injury.

Language: Английский

Citations

17
Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies DOI Creative Commons

Mahmoud G. El Baassiri,

Zachariah Raouf,

Sarah Badin

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 10, 2024

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with high risk of psychiatric neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack effective treatments underscore urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as crucial bidirectional pathway connecting gastrointestinal (GI) system through an intricate network neuronal, hormonal, immunological pathways. Four main pathways are primarily implicated this crosstalk, including systemic immune system, autonomic enteric nervous systems, neuroendocrine microbiome. TBI induces profound changes gut, initiating unrestrained vicious cycle that exacerbates axis. Alterations gut include mucosal damage malabsorption nutrients/electrolytes, disintegration intestinal barrier, increased infiltration cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction disruption (ENS) (ANS). Collectively, these further contribute to neuroinflammation neurodegeneration via gut-brain In review article, we elucidate roles various anti-inflammatory pharmacotherapies capable attenuating dysregulated inflammatory response along TBI. These agents hormones such serotonin, ghrelin, progesterone, ANS regulators beta-blockers, lipid-lowering drugs like statins, flora modulators probiotics antibiotics. They attenuate by targeting distinct both post-TBI. exhibit promising potential mitigating inflammation enhancing neurocognitive outcomes patients.

Language: Английский

Citations

12
Crosstalk Between the Nervous System and Systemic Organs in Acute Brain Injury DOI
Denise Battaglini, Silvia De Rosa, Daniel Agustín Godoy

et al.

Neurocritical Care, Journal Year: 2023, Volume and Issue: 40(1), P. 337 - 348

Published: April 20, 2023

Language: Английский

Citations

18
Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury DOI Creative Commons
Hiren R. Modi,

Sudeep Musyaju,

Meaghan Ratcliffe

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 303 - 303

Published: Feb. 29, 2024

Traumatic brain injury (TBI) is a major global health problem that affects both civilian and military populations worldwide. Post-injury acute, sub-acute, chronic progression of secondary processes may contribute further to other neurodegenerative diseases. However, there are no approved therapeutic options available can attenuate TBI-related progressive pathophysiology. Recent advances in preclinical research have identified mitochondria-centric redox imbalance, bioenergetics failure calcium dysregulation play crucial role after TBI. Mitochondrial antioxidants an important regulating homeostasis. Based on the proven efficacy clinical compounds targeting numerous pathways trigger innate antioxidant defense, we be able alleviate TBI pathology by primarily focusing preserving post-injury mitochondrial cerebral function. In this review, will discuss novel mitochondria-targeted compounds, which offer high capability successful translation for management near future.

Language: Английский

Citations

8
The role of the microbiota–gut–brain axis in long‐term neurodegenerative processes following traumatic brain injury DOI Creative Commons
Li Shan Chiu, Ryan S. Anderton

European Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 57(2), P. 400 - 418

Published: Dec. 10, 2022

Traumatic brain injury (TBI) can be a devastating and debilitating disease to endure. Due improvements in clinical practice, declining mortality rates have led research into the long-term consequences of TBI. For example, incidence severity TBI been associated with an increased susceptibility developing neurodegenerative disorders, such as Parkinson's or Alzheimer's disease. However, mechanisms linking this alarming association are yet fully understood. Recently, there has groundswell evidence implicating microbiota-gut-brain axis pathogenesis these diseases. Interestingly, survivors often report gastrointestinal complaints animal studies demonstrated dysfunction dysbiosis following injury. Autonomic dysregulation chronic inflammation appear main driver pathologies. Consequently, review will explore potential role development diseases

Language: Английский

Citations

28
The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury DOI
Mega O. Oyovwi, Onoriode Andrew Udi

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 62(4), P. 4576 - 4590

Published: Oct. 28, 2024

Language: Английский

Citations

6
Critical Knowledge Gaps and Future Priorities Regarding the Intestinal Barrier Damage After Traumatic Brain Injury DOI

He Guangliang,

Tao Wang,

Wang Danxin

et al.

World Neurosurgery, Journal Year: 2024, Volume and Issue: 188, P. 136 - 149

Published: May 22, 2024

Language: Английский

Citations

5
The Intestinal Microbiome after Traumatic Injury DOI Creative Commons
Jennifer A. Munley, Stacey L. Kirkpatrick, Gwendolyn S. Gillies

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(8), P. 1990 - 1990

Published: Aug. 2, 2023

The intestinal microbiome plays a critical role in host immune function and homeostasis. Patients suffering from—as well as models representing—multiple traumatic injuries, isolated organ system trauma, various severities of injury have been studied an area interest the dysregulation systemic inflammation which occur after trauma. These studies also demonstrate changes gut diversity even microbial composition, with transition to pathobiome state. In addition, sex has identified biological variable influencing alterations Therapeutics such fecal transplantation utilized ameliorate not only these but may play recovery postinjury. This review summarizes that postinjury, either or multiple along proposed mechanisms for future directions field.

Language: Английский

Citations

11