Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-Based Therapies for Inflammatory Bowel Diseases DOI Creative Commons
Louis Cohen, Judy H. Cho, Dirk Gevers

et al.

Gastroenterology, Journal Year: 2019, Volume and Issue: 156(8), P. 2174 - 2189

Published: March 14, 2019

The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis physiology. Imbalances in the microbiome aberrant immune responses to gut bacteria can disrupt are associated with inflammatory bowel diseases (IBDs) humans colitis mice. We review genetic variants IBD their effects on microbiome, response, disease pathogenesis. which includes microbial antigens, adjuvants, metabolic products, affects development function mucosa, influencing gut. Therefore, strategies manipulate might be used treatment IBD. microbe-based therapies for potential engineer patients' microbiota. discuss how studies patients mouse models have advanced our understanding interactions between factors challenges Inflammatory include Crohn (CD) ulcerative (UC), chronic develop through complex among genetic, immune, environmental, factors.1Abraham C. Medzhitov R. Interactions host innate system microbes disease.Gastroenterology. 2011; 140: 1729-1737Abstract Full Text PDF PubMed Scopus (314) Google Scholar, 2Belkaid Y. Hand T.W. Role immunity inflammation.Cell. 2014; 157: 121-141Abstract (1124) 3Sun M. He Cong et al.Regulatory cells regulation response microbiota.Mucosal Immunol. 2015; 8: 969-978Crossref (95) Scholar Dysregulation any components this network result inflammation Genetic identified regulators altered IBD—many these control microbes.4Hall A.B. Tolonen A.C. Xavier R.J. Human variation disease.Nat Rev Genet. 2017; 18: 690-699Crossref (108) 5Luca F. Kupfer S.S. Knights D. al.Functional genomics host–microbiome humans.Trends 2018; 34: 30-40Abstract (0) Variants risk been NOD2, ATG16L1, CARD9, CLEC7A.6Khor B. Gardet A. Genetics pathogenesis disease.Nature. 474: 307-317Crossref (1187) genes detection perturb promote inflammation. It important distinguish mediate pathogens from overall ecology, also affected by environmental (diet, medications, geography).7Rothschild Weissbrod O. Barkan E. al.Environment dominates over genetics shaping human microbiota.Nature. 555: 210-215Crossref (362) However, as we study mechanisms affect microbes, learn more about do so identify new targets diagnosis Studies model systems indicated modified increase or decrease severity introduction effectors, such lipids, small molecules, proteins, sugars. During past decade, interest has increased due number perceived safety therapies, correct one causes disease, rather than symptoms. Increased part insights antibiotics, probiotics, recently fecal transplantation (FMT) other disorders.8Hoffmann D.E. Palumbo F.B. 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Time check: evidence HLA-B27 spondylitis microbiome.Arthritis Rheum. 63: 3195-3198Crossref 68Olivares Neef Castillejo HLA-DQ2 selects infants high developing coeliac 64: 406-417Crossref (116) showed correlation HLA alleles permeability.69Scher J.U. Sczesnak Longman R.S. al.Expansion Prevotella copri correlates enhanced arthritis.Elife. 2: e01202Crossref Scho

Language: Английский

Gut microbial molecules in behavioural and neurodegenerative conditions DOI
Brittany D. Needham, Rima Kaddurah‐Daouk, Sarkis K. Mazmanian

et al.

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(12), P. 717 - 731

Published: Oct. 16, 2020

Language: Английский

Citations

274

Gut microbiome diversity is associated with sleep physiology in humans DOI Creative Commons
Robert P. Smith, Cole Easson, Sarah M. Lyle

et al.

PLoS ONE, Journal Year: 2019, Volume and Issue: 14(10), P. e0222394 - e0222394

Published: Oct. 7, 2019

The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that sleep quality. Previous studies have examined deprivation and yielded conflicting results. A recent study found leads to changes in composition while a different does not lead microbiome. Accordingly, relationship between physiology remains unclear. To address this uncertainty, we used actigraphy quantify measures coupled with sampling determine how correlates various of physiology. We measured immune system biomarkers carried out neurobehavioral assessment as these variables might modify composition. total diversity was positively correlated increased efficiency time, negatively wake after onset. positive correlations interleukin-6, cytokine previously noted for its effects on sleep. Analysis revealed within phyla richness Bacteroidetes Firmicutes were efficiency, interleukin-6 concentrations abstract thinking. Finally, several taxa (Lachnospiraceae, Corynebacterium, Blautia) measures. Our findings initiate linkages composition, physiology, cognition. They may mechanisms improve manipulation

Language: Английский

Citations

271

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

255

Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions DOI Open Access

Suganya Kanmani,

Byung‐Soo Koo

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7551 - 7551

Published: Oct. 13, 2020

The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has largest and vulnerable surface with desirable features to observe foods, nutrients, environmental factors, well differentiate commensals, invading pathogens, others. It is well-known a strong connection central nervous system (CNS) in context health disease. A healthy diverse microbes vital for normal brain functions emotional behaviors. In addition, CNS controls most aspects GI physiology. molecular interaction between gut/microbiome complex bidirectional, ensuring maintenance homeostasis proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, metabolites-dependent pathways. Changes bidirectional relationship GIT are linked pathogenesis neurological disorders; therefore, microbiota/gut-and-brain axis emerging widely accepted concept. this review, we summarize recent findings supporting role microbiota immune on development disorders. highlight advances improving diseases by probiotics/prebiotics/synbiotics fecal transplantation via concept gut–brain axis.

Language: Английский

Citations

246

The future of rodent models in depression research DOI
Anand Gururajan, Andreas Reif, John F. Cryan

et al.

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(11), P. 686 - 701

Published: Oct. 2, 2019

Language: Английский

Citations

226

Gut Bacteria and Neurotransmitters DOI Creative Commons
Leon M. T. Dicks

Microorganisms, Journal Year: 2022, Volume and Issue: 10(9), P. 1838 - 1838

Published: Sept. 14, 2022

Gut bacteria play an important role in the digestion of food, immune activation, and regulation entero-endocrine signaling pathways, but also communicate with central nervous system (CNS) through production specific metabolic compounds, e.g., bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT) histamine. Afferent vagus nerve (VN) fibers that transport signals from gastro-intestinal tract (GIT) gut microbiota to brain are linked receptors esophagus, liver, pancreas. In response these stimuli, sends back entero-epithelial cells via efferent VN fibers. Fibers not direct contact wall or intestinal microbiota. Instead, reach 100 500 million neurons enteric (ENS) submucosa myenteric plexus wall. The modulation, development, renewal ENS controlled by microbiota, especially those ability produce metabolize hormones. Signals generated hypothalamus pituitary adrenal glands hypothalamic axis (HPA). SCFAs produced adhere free (FFARs) on surface epithelial (IECs) interact enter circulatory system. alter synthesis degradation neurotransmitters. This review focuses effect have neurotransmitters vice versa.

Language: Английский

Citations

222

Microbiota-derived metabolites as drivers of gut–brain communication DOI Creative Commons
Hany Ahmed, Quentin Leyrolle, Ville Koistinen

et al.

Gut Microbes, Journal Year: 2022, Volume and Issue: 14(1)

Published: July 28, 2022

Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The microbes transform metabolize dietary- host-derived molecules generating diverse group metabolites local systemic effects. bi-directional communication between brain residing gut, so-called gut–brain axis, consists network immunological, neuronal, endocrine signaling pathways. Although full variety mechanisms crosstalk is yet to be established, existing data demonstrates that single metabolite or its derivatives are likely among key inductors within axis communication. However, more research needed understand molecular underlying how alter functions, examine if different interventional approaches targeting could used prevention treatment neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic ZO Zonula occludens proteins

Language: Английский

Citations

211

Microbiota Metabolites in Health and Disease DOI Open Access
Justin L. McCarville, Grischa Y. Chen, Víctor D. Cuevas

et al.

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 147 - 170

Published: April 26, 2020

Metabolism is one of the strongest drivers interkingdom interactions—including those between microorganisms and their multicellular hosts. Traditionally thought to fuel energy requirements provide building blocks for biosynthetic pathways, metabolism now appreciated its role in providing metabolites, small-molecule intermediates generated from metabolic processes, perform various regulatory functions mediate symbiotic relationships microbes Here, we review recent advances our mechanistic understanding how microbiota-derived metabolites orchestrate support physiological responses host, including immunity, inflammation, defense against infections, metabolism. Understanding metabolically communicate with hosts will us an opportunity better describe a host interacts all microbes—beneficial, pathogenic, commensal—and discover new ways treat microbial-driven diseases.

Language: Английский

Citations

199

Gut Microbiome in Progressive Multiple Sclerosis DOI
Laura M. Cox,

Amir Hadi Maghzi,

Shirong Liu

et al.

Annals of Neurology, Journal Year: 2021, Volume and Issue: 89(6), P. 1195 - 1211

Published: April 20, 2021

Objective This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates clinical disease. Methods We sequenced microbiota from healthy controls relapsing–remitting MS (RRMS) patients correlated levels of bacteria with features disease, including Expanded Disability Status Scale (EDSS), quality life, brain magnetic resonance imaging lesions/atrophy. colonized mice MS‐derived Akkermansia induced experimental autoimmune encephalomyelitis (EAE). Results Microbiota β‐diversity differed between but did not differ RRMS or based on disease‐modifying therapies. Disease status had greatest effect β‐diversity, followed by body mass index, race, sex. In both RRMS, we found increased Clostridium bolteae , Ruthenibacterium lactatiformans decreased Blautia wexlerae Dorea formicigenerans Erysipelotrichaceae CCMM . Unique MS, elevated Enterobacteriaceae g24 FCEY Agathobaculum Several species were associated higher EDSS fatigue scores. Contrary view that has a detrimental role, linked lower disability, suggesting beneficial role. Consistent this, isolated ameliorated EAE, which reduction RORγt+ IL‐17–producing γδ T cells. Interpretation Whereas some alterations are shared relapsing identified unique measures Furthermore, may be compensatory response microbiome. ANN NEUROL 2021;89:1195–1211

Language: Английский

Citations

198

Gamma-aminobutyric acid and probiotics: Multiple health benefits and their future in the global functional food and nutraceuticals market DOI Creative Commons
Lucía Diez-Gutiérrez, Leire San Vicente, Luis Javier R. Barrón

et al.

Journal of Functional Foods, Journal Year: 2019, Volume and Issue: 64, P. 103669 - 103669

Published: Nov. 19, 2019

Probiotics have attracted growing interest in recent decades due to their multiple health benefits. The synergistic relationship between probiotics and prebiotics can enhance the production of metabolites called postbiotics, which are gaining increasing importance because beneficial functions gastrointestinal tract influence on different organs tissues. Notable among postbiotics is gamma-aminobutyric acid, plays an essential role prevention neural disease, type 1 diabetes, cancer, immunological disorders asthma. Generally, acid produced by lactic bacteria, under certain conditions produce a high amount this amino acid. food industry has leveraged capacity develop functional foods enriched with

Language: Английский

Citations

195