Inferring the role of the microbiome on survival in patients treated with immune checkpoint inhibitors: causal modeling, timing, and classes of concomitant medications DOI Creative Commons
Daniel Spakowicz, Rebecca Hoyd, Mitchell Muniak

et al.

BMC Cancer, Journal Year: 2020, Volume and Issue: 20(1)

Published: May 6, 2020

Abstract Background The microbiome has been shown to affect the response Immune Checkpoint Inhibitors (ICIs) in a small number of cancers and preclinical models. Here, we sought broadly survey identify those which may play prognostic role using retrospective analyses patients with advanced cancer treated ICIs. Methods We conducted analysis 690 who received ICI therapy for cancer. used literature review define causal model relationship between medications, microbiome, guide abstraction electronic health records. Medications precedent changes included antibiotics, corticosteroids, proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories statins. tested effect medication timing on overall survival (OS) evaluated robustness effects each Finally, compared size observed different classes antibiotics taxa that have correlated culture-based antibiotic susceptibilities. Results Of medications assessed, only corticosteroids significantly associated shorter OS. hazard ratios (HRs) were highest near start treatment but remained significant when given prior ICI. Antibiotics OS even controlling multiple factors such as Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index score, stage. When grouping by class, β-lactams showed strongest association across all cancers. Conclusions strength correlations after confounding are consistent involvement ICIs several

Language: Английский

The Role of Microbiome in Insomnia, Circadian Disturbance and Depression DOI Creative Commons
Yuanyuan Li, Yanli Hao, Fang Fan

et al.

Frontiers in Psychiatry, Journal Year: 2018, Volume and Issue: 9

Published: Dec. 5, 2018

Good sleep and mood are important for health keeping active. Numerous studies have suggested that the incidence of insomnia depressive disorder linked to biological rhythms, immune function nutrient metabolism, but exact mechanism is not yet clear. There considerable evidence showing gut microbiome only affects digestive, metabolic, functions host also regulates mental states through microbiome-gut-brain axis. Preliminary indicates microorganisms circadian genes can interact with each other. The characteristics gastrointestinal metabolism related host's rhythm. Moreover, emotion physiological stress affect composition microorganisms. inflammation may be loss, misalignment, affective disorders metabolic disease. In this review article, we discuss various how its activities rhythms emotions host. Exploring effects on depression will help further our understanding pathogenesis disorders. It therefore regulate maintain a normal micro-ecological environment in patients when treating

Language: Английский

Citations

234
Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice DOI Creative Commons
Alessio Cortellini, Marco Tucci, Vincenzo Adamo

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(2), P. e001361 - e001361

Published: Nov. 1, 2020

Background Concomitant medications, such as steroids, proton pump inhibitors (PPI) and antibiotics, might affect clinical outcomes with immune checkpoint inhibitors. Methods We conducted a multicenter observational retrospective study aimed at evaluating the impact of concomitant medications on outcomes, by weighing their associations baseline characteristics (including performance status, burden disease body mass index) underlying causes for prescription. This analysis included consecutive stage IV patients cancer, who underwent treatment single agent antiprogrammed death-1/programmed death ligand-1 (PD-1/PD-L1) standard doses schedules medical oncology departments 20 Italian institutions. Each medication taken immunotherapy initiation was screened collected into key categories follows: corticosteroids, gastric acid suppressants - PPIs), statins other lipid-lowering agents, aspirin, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors/Angiotensin II receptor blockers, calcium antagonists, β-blockers, metformin oral antidiabetics, opioids. Results From June 2014 to March 2020, 1012 were in analysis. Primary tumors were: non-small cell lung cancer (52.2%), melanoma (26%), renal carcinoma (18.3%) others (3.6%). Baseline (HR 1.60 (95% CI 1.14 2.25), p=0.0064), aspirin 1.47 1.04 2.08, p=0.0267) β-blockers 1.76 1.16 2.69), p=0.0080) confirmed be independently related an increased objective response rate. Patients receiving cancer-related steroids 1.72 1.43 2.07), p<0.0001), prophylactic systemic antibiotics 1.85 1.23 2.78), p=0.0030), 1.29 1.09 1.53), p=0.0021), PPIs 1.26 1.07 1.48), p=0.0050), anticoagulants CI: 1.77), p=0.0007) opioids 1.71 1.28 2.28), p=0.0002) have significantly higher risk progression. 2.16 2.65), 1.93 1.25 2.98), 1.06 1.57), p=0.0091), PPI 1.52), p=0.0172), 1.45 1.84), p=0.0024) 1.53 1.11 2.11), p=0.0098) death. Conclusion association between administered indication, worse PD-1/PD-L1 inhibitors, which can assumed immune-modulating detrimental effects.

Language: Английский

Citations

205
A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies DOI Creative Commons
Bruno K. Rodiño‐Janeiro, María Vicario, Carmen Alonso

et al.

Advances in Therapy, Journal Year: 2018, Volume and Issue: 35(3), P. 289 - 310

Published: March 1, 2018

Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain altered habit. The origin seems to be multifactorial still not well defined for different subtypes. Genetic, epigenetic sex-related modifications functioning nervous immune-endocrine supersystems regulation brain-gut physiology bile acid production absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary life event-related factors enhance epithelial permeability elicit mucosal microinflammation, immune activation dysbiosis. Notably, strong evidence supports role bacterial, viral parasitic infections triggering IBS, targeting microbiota promising view positive response microbiota-related therapies some patients. However, lack highly predictive diagnostic biomarkers complexity heterogeneity IBS patients make management difficult unsatisfactory many cases, reducing patient health-related quality increasing sanitary burden. This article reviews specific alterations interventions gut including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation other potential future approaches useful diagnosis, prevention treatment IBS.

Language: Английский

Citations

196
Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders DOI

Laure Tabouy,

Dimitry Getselter,

Ziv Oren

et al.

Brain Behavior and Immunity, Journal Year: 2018, Volume and Issue: 73, P. 310 - 319

Published: May 19, 2018

Language: Английский

Citations

167
When Rhythms Meet the Blues: Circadian Interactions with the Microbiota-Gut-Brain Axis DOI Creative Commons
Emily M. Teichman, Kenneth J. O’Riordan, Cormac G. M. Gahan

et al.

Cell Metabolism, Journal Year: 2020, Volume and Issue: 31(3), P. 448 - 471

Published: March 1, 2020

Language: Английский

Citations

145
Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis DOI Creative Commons
Chun‐Yuan Chen,

Shan‐Shan Rao,

Tao Yue

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(15)

Published: April 13, 2022

Osteonecrosis of the femoral head (ONFH) commonly occurs after glucocorticoid (GC) therapy. The gut microbiota (GM) participates in regulating host health, and its composition can be altered by GC. Here, this study demonstrates that cohousing with healthy mice or colonization GM from normal attenuates GC-induced ONFH. 16S rRNA gene sequencing shows rescues reduction Lactobacillus animalis. Oral supplementation L. animalis mitigates ONFH increasing angiogenesis, augmenting osteogenesis, reducing cell apoptosis. Extracellular vesicles (L. animalis-EVs) contain abundant functional proteins enter to exert proangiogenic, pro-osteogenic, antiapoptotic effects, while abundance is reduced exposure Our suggests involved protecting transferring bacterial EVs, loss EVs associated development

Language: Английский

Citations

117
Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis DOI Creative Commons
Jody Rusch, Brian T. Layden, Lara R. Dugas

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 19, 2023

Cognitive function in humans depends on the complex and interplay between multiple body systems, including hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells has a genetic potential that exceeds of genome, plays crucial role this interplay. microbiota-gut-brain (MGB) axis is bidirectional signalling pathway operates through neural, endocrine, immune, metabolic pathways. One major neuroendocrine systems responding to stress HPA produces glucocorticoids such as cortisol corticosterone rodents. Appropriate concentrations are essential for normal neurodevelopment function, well cognitive processes learning memory, studies have shown microbes modulate throughout life. Stress can significantly impact MGB via other Animal research advanced our understanding these mechanisms pathways, leading paradigm shift conceptual thinking about influence microbiota health disease. Preclinical trials currently underway determine how animal models translate humans. In review article, we summarize current knowledge relationship axis, cognition, provide an overview main findings conclusions broad field.

Language: Английский

Citations

117
Exposure to prescribed medication in early life and impacts on gut microbiota and disease development DOI Creative Commons
Huan Huang,

Jiayin Jiang,

Xinyu Wang

et al.

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 68, P. 102428 - 102428

Published: Jan. 23, 2024

The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health later life. Early-life pharmaceutical exposure, mainly referring to exposure pregnancy, childbirth, infancy, may change the structure function of affect health. In this Review, we describe how healthy established We summarise commonly prescribed medications life, including antibiotics, acid suppressant other such as antidepressants, analgesics steroid hormones, discuss these medication-induced changes are involved pathological process diseases, infections, inflammatory bowel disease, metabolic allergic diseases neurodevelopmental disorders. Finally, review some critical methods dietary therapy, probiotics, prebiotics, faecal transplantation, genetically engineered phages, vagus nerve stimulation aiming provide new strategy prevention adverse outcomes caused by

Language: Английский

Citations

22
Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism DOI
Katya Frazier, Eugene B. Chang

Trends in Endocrinology and Metabolism, Journal Year: 2019, Volume and Issue: 31(1), P. 25 - 36

Published: Nov. 3, 2019

Language: Английский

Citations

126
Mitochondrial quality surveillance as a therapeutic target in myocardial infarction DOI
Hang Zhu, Sam Toan,

David Mui

et al.

Acta Physiologica, Journal Year: 2020, Volume and Issue: 231(3)

Published: Dec. 3, 2020

Abstract Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. As mitochondrial dysfunction critically contributes to the pathogenesis MI, intensive research focused on development therapeutic strategies targeting homeostasis. Mitochondria possess quality control system which maintains restores their structure function by regulating fission, fusion, biogenesis, degradation death. In response slight damage such as transient hypoxia or mild oxidative stress, metabolism shifts from phosphorylation glycolysis, in order reduce oxygen consumption maintain ATP output. Mitochondrial dynamics are also activated modify shape structure, meet cardiomyocyte energy requirements through augmenting reducing mass. When damaged mitochondria cannot be repaired, poorly structured will degraded mitophagy, process often accompanied biogenesis. Once insult severe enough induce lethal cell, death pathway activation an inevitable consequence, apoptosis necrosis program initiated remove cells. surveillance hierarchical preserving defending cardiomyocytes against stress. A failure this has been regarded one potential pathologies underlying MI. review, we discuss recent findings focusing role highlight available approaches during

Language: Английский

Citations

125