Multi-Omics Analysis Reveals Aberrant Gut-Metabolome-Immune Network in Schizophrenia DOI Creative Commons
Yajuan Fan, Yuan Gao,

Qingyan Ma

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 3, 2022

Schizophrenia (SCZ) is associated with several immune dysfunctions, including elevated levels of pro-inflammatory cytokines. Microorganisms and their metabolites have been found to regulate the system, that intestinal microbiota significantly disturbed in schizophrenic patients. To systematically investigate aberrant gut-metabolome-immune network schizophrenia, we performed an integrative analysis microbiota, serum metabolome, inflammatory cytokines 63 SCZ patients 57 healthy controls using a multi-omics strategy. Eighteen differentially abundant metabolite clusters were altered displayed higher cytokine levels, significant increase decrease anti-inflammatory (such as oleic acid linolenic acid). The bacterial co-abundance groups gut more numerous stronger correlations circulating than By integrating these data, identified certain bacteria might affect by modulating host metabolites, such amino acids fatty acids. A random forest model was constructed based on omics seven α-diversity able accurately distinguish cases from area under receiver operating characteristic curve 0.99. Our results indicated may influence responses regulating metabolic processes. These findings suggest mechanism which microbial-derived regulated insights into diagnosis treatment mental disorders microbial-immune system future.

Language: Английский

The role of itaconate in host defense and inflammation DOI Creative Commons
Christian G. Peace, Luke O'neill

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(2)

Published: Jan. 17, 2022

Macrophages exposed to inflammatory stimuli including LPS undergo metabolic reprogramming facilitate macrophage effector function. This supports phagocytic function, cytokine release, and ROS production that are critical protective responses. The Krebs cycle is a central pathway within all mammalian cell types. In activated macrophages, distinct breaks in the regulate function through accumulation of several metabolites were recently shown have signaling roles immunity. One metabolite accumulates macrophages because disturbance itaconate, which derived from cis-aconitate by enzyme decarboxylase (ACOD1), encoded immunoresponsive gene 1 (Irg1). Review focuses on itaconate’s emergence as key immunometabolite with diverse immunity inflammation. These include inhibition succinate dehydrogenase (which controls levels succinate, multiple inflammation), glycolysis at will limit activation antiinflammatory transcription factors Nrf2 ATF3, NLRP3 inflammasome. Itaconate its derivatives effects preclinical models sepsis, viral infections, psoriasis, gout, ischemia/reperfusion injury, pulmonary fibrosis, pointing possible itaconate-based therapeutics for range diseases. intriguing continues yield fascinating insights into role host defense

Language: Английский

Citations

276
The functional roles of TCA cycle metabolites in cancer DOI
Joseph Eniafe, Shuai Jiang

Oncogene, Journal Year: 2021, Volume and Issue: 40(19), P. 3351 - 3363

Published: April 16, 2021

Language: Английский

Citations

185
Metabolic inflammation in heart failure with preserved ejection fraction DOI
Gabriele G. Schiattarella, Daniele Rodolico, Joseph A. Hill

et al.

Cardiovascular Research, Journal Year: 2020, Volume and Issue: 117(2), P. 423 - 434

Published: July 7, 2020

Abstract One in 10 persons the world aged 40 years and older will develop syndrome of HFpEF (heart failure with preserved ejection fraction), most common form chronic cardiovascular disease for which no effective therapies are currently available. Metabolic disturbance inflammatory burden contribute importantly to pathogenesis. The interplay within these two biological processes is complex; indeed, it now becoming clear that notion metabolic inflammation—metainflammation—must be considered central pathophysiology. Inflammation metabolism interact over course progression, likely impact treatment prevention. Here, we discuss evidence support a causal, mechanistic role metainflammation shaping HFpEF, proposing framework comorbidities profoundly cardiac pathways syndrome.

Language: Английский

Citations

175
Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses DOI Creative Commons
Inseok Choi,

Hyewon Son,

Jea-Hyun Baek

et al.

Life, Journal Year: 2021, Volume and Issue: 11(1), P. 69 - 69

Published: Jan. 19, 2021

The tricarboxylic acid cycle (TCA) is a series of chemical reactions used in aerobic organisms to generate energy via the oxidation acetylcoenzyme A (CoA) derived from carbohydrates, fatty acids and proteins. In eukaryotic system, TCA occurs completely mitochondria, while intermediates are retained inside mitochondria due their polarity hydrophilicity. Under cell stress conditions, can become disrupted release contents, which act as danger signals cytosol. Of note, may also leak dysfunctioning regulate cellular processes. Increasing evidence shows that metabolites substantially involved regulation immune responses. this review, we aimed provide comprehensive systematic overview molecular mechanisms each intermediate play key roles regulating immunity discuss its implication for activation suppression.

Language: Английский

Citations

158
Crosstalk between glucose metabolism, lactate production and immune response modulation DOI
Lei Ye, Yi Jiang, Mingming Zhang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2022, Volume and Issue: 68, P. 81 - 92

Published: Nov. 7, 2022

Language: Английский

Citations

149
A guide to interrogating immunometabolism DOI
Kelsey Voss, Hanna S. Hong, Jackie E. Bader

et al.

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(10), P. 637 - 652

Published: April 15, 2021

Language: Английский

Citations

125
Myeloid-derived itaconate suppresses cytotoxic CD8+ T cells and promotes tumour growth DOI
Hongyun Zhao, Da Teng,

Lifeng Yang

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(12), P. 1660 - 1673

Published: Nov. 14, 2022

Language: Английский

Citations

105
The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases DOI Creative Commons
Xuan Shi, Huanping Zhou, Juan Wei

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 58, P. 102553 - 102553

Published: Nov. 24, 2022

Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle disrupted. derived from cis-aconitate decarboxylation by decarboxylase (ACOD1) mitochondrial matrix and also known as immune-responsive gene 1 (IRG1). Studies have demonstrated itaconate plays an important role regulating signal transduction posttranslational modification through its immunoregulatory activities. bridge among metabolism, inflammation, oxidative stress, immune response. This review summarizes structural characteristics classical pathways itaconate, derivatives, compounds release itaconate. Here, mechanisms action, including transcriptional regulation ATF3/IκBζ axis type I IFN, protein KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, TFEB, succinate dehydrogenase glycolytic enzyme presented. Moreover, roles diseases related to inflammation stress induced autoimmune responses, viruses, sepsis IRI discussed this review. We hope information provided will help increase understanding cellular metabolism improve clinical treatment stress.

Language: Английский

Citations

72
Lacticaseibacillus rhamnosus Probio-M9 enhanced the antitumor response to anti-PD-1 therapy by modulating intestinal metabolites DOI Creative Commons
Guangqi Gao, Siyuan Shen, Tao Zhang

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 91, P. 104533 - 104533

Published: April 5, 2023

Probiotics have been increasingly proposed for enhancing immune checkpoint blockade (ICB) treatments against cancer. However, its causal relationship with immunotherapeutic efficacy remains unclear, which promoted us to explore if and how probiotic Lacticaseibacillus rhamnosus Probio-M9 manipulates gut microbiome expected outcomes.We evaluated the effects of on anti-PD-1 treatment colorectal cancer in mice via a multi-omics approach. We defined mechanisms Probio-M9-mediated antitumor immunity by comprehensive analyses metagenome metabolites commensal microbes as well immunologic factors serum metabolome host.The results indicated that intervention strengthened anti-PD-1-based tumor inhibition. Both prophylactic therapeutic administration showed conspicuous performance controlling growth ICB treatment. The supplement modulated enhanced immunotherapy response through promoting beneficial (e.g., Lactobacillus Bifidobacterium animalis), producing including butyric acids gut, accumulating blood-derived α-ketoglutaric acid, N-acetyl-l-glutamic acid pyridoxine particular, infiltration activation cytotoxic T lymphocytes (CTLs) suppressing function regulatory cells (Tregs) microenvironment (TME). Subsequently, we found was transmissible transplanting either post-probiotic-treatment or intestinal new tumor-bearing mice.This study offered valuable insight into role correcting defects microbiota compromised efficacy, can be used an alternative synergetic agent clinical treatment.This research supported Research Fund National Key R&D Program China (2022YFD2100702), Inner Mongolia Science Technology Major Projects (2021ZD0014), Agriculture System MOF MARA.

Language: Английский

Citations

43
A metabolic perspective of the neutrophil life cycle: new avenues in immunometabolism DOI Creative Commons

Mehakpreet K. Thind,

Holm H. Uhlig, Michael Glogauer

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Neutrophils are the most abundant innate immune cells. Multiple mechanisms allow them to engage a wide range of metabolic pathways for biosynthesis and bioenergetics mediating biological processes such as development in bone marrow antimicrobial activity ROS production NET formation, inflammation tissue repair. We first discuss recent work on neutrophil functions regulate granulopoiesis, migration trafficking well effector functions. then syndromes with impaired that influenced by genetic environmental factors nutrient availability usage. Here, we particularly focus role specific macronutrients, glucose, fatty acids, protein, micronutrients vitamin B3, regulating biology how this regulation impacts host health. A special section review primarily discusses ways deficiencies could impact increase infection susceptibility. emphasize biochemical approaches explore metabolism relation Lastly, opportunities challenges neutrophil-centered therapeutic immune-driven diseases highlight unanswered questions guide future discoveries.

Language: Английский

Citations

23