Gut liver brain axis in diseases: the implications for therapeutic interventions

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

Published: Dec. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Language: Английский

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Understanding neuroimmune interactions in disorders of gut–brain interaction: from functional to immune-mediated disorders

Gut, Journal Year: 2023, Volume and Issue: 72(4), P. 787 - 798

Published: Jan. 19, 2023

Functional gastrointestinal disorders—recently renamed into disorders of gut–brain interaction—such as irritable bowel syndrome and functional dyspepsia are highly prevalent conditions with bothersome abdominal symptoms in the absence structural abnormalities. While traditionally considered motility or even psychosomatic conditions, our understanding pathophysiology has evolved significantly over last two decades. Initial observations subtle mucosal infiltration immune cells, especially mast cells eosinophils, since recently being backed up by mechanistic evidence demonstrating increased release nociceptive mediators intestinal epithelium. These can activate sensitised neurons leading to visceral hypersensitivity symptoms. The interaction between activation an impaired barrier function gut is most likely a bidirectional one alterations microbiota, psychological stress food components upstream players pathophysiology. Only few immune-targeting treatments currently available, but improved through multidisciplinary scientific approach will hopefully identify novel, more precise treatment targets ultimately better outcomes.

Language: Английский

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The Role of the FODMAP Diet in IBS

Nutrients, Journal Year: 2024, Volume and Issue: 16(3), P. 370 - 370

Published: Jan. 26, 2024

The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the works still not completely understood. These mechanisms encompass only traditionally known factors such as luminal distension induced by gas water but also recent evidence on role of FOMAPs in modulation visceral hypersensitivity, increases intestinal permeability, induction microbiota changes, production short-chain fatty acids (SCFAs), well metabolomics alterations motility. Although most supporting quality, trials have confirmed its effectiveness, even though majority pertains to restriction phase effectiveness relieving abdominal bloating pain. This review examines potential pathophysiological provides an overview existing across various IBS subtypes. Key considerations use include challenges disadvantages associated practical implementation, including need professional guidance, variations individual responses, concerns related microbiota, nutritional deficiencies, development constipation, necessity excluding eating disorder before commencing diet, scarcity long-term data. Despite recognized efficacy symptom management, acknowledging these limitations becomes imperative nuanced comprehension managing IBS. By investigating subtypes addressing emerging modulations alongside limitations, this aims serve valuable resource healthcare practitioners, researchers, navigating intricate landscape

Language: Английский

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Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments

Gastroenterology, Journal Year: 2024, Volume and Issue: 166(6), P. 976 - 994

Published: Feb. 5, 2024

Cofounder of pHarm Therapeutics Inc., a company that is developing pH sensitive analgesics selectively target sites inflammation where pain originates.PCK

Language: Английский

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Gut microbiota and intestinal immunity—A crosstalk in irritable bowel syndrome

Immunology, Journal Year: 2024, Volume and Issue: 172(1), P. 1 - 20

Published: Jan. 4, 2024

Irritable bowel syndrome (IBS), one of the most prevalent functional gastrointestinal disorders, is characterized by recurrent abdominal pain and abnormal defecation habits, resulting in a severe healthcare burden worldwide. The pathophysiological mechanisms IBS are multi-factorially involved, including food antigens, visceral hypersensitivity reactions, brain–gut axis. Numerous studies have found that gut microbiota intestinal mucosal immunity play an important role development crosstalk with multiple mechanisms. Therefore, based on existing evidence, this paper elaborates damage activation disturbance closely related to progression IBS. Combined application prospect, it also provides references for further in-depth exploration clinical practice.

Language: Английский

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Neuroimmune Interactions in the Intestine

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 489 - 519

Published: June 28, 2024

Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role this cross talk for gut homeostasis modulation inflammatory infectious intestinal diseases. In review, we describe innervation by intrinsic extrinsic neurons then focus on bidirectional communication between immune cells. First, highlight contribution neuronal subtypes development colitis discuss different epithelial cell types that are regulated via release neuropeptides neurotransmitters. Next, review inflammation visceral hypersensitivity summarize how mediators induce peripheral central sensitization gut-innervating sensory neurons. Finally, outline importance cells microbiota survival function populations at during bacterial helminth infection.

Language: Английский

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Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Gut, Journal Year: 2022, Volume and Issue: 72(3), P. 590 - 599

Published: Oct. 28, 2022

Objective To appraise the evidence that pathophysiological mechanisms and individualised treatment directed at those provide an alternative approach to of patients with irritable bowel syndrome (IBS). Design A PubMED-based literature review IBS was conducted independently by two authors, any differences perspective or interpretation were resolved following discussion. Results The availability several noninvasive clinical tests can responsible for symptom generation in IBS, including rectal evacuation disorders, abnormal transit, visceral hypersensitivity hypervigilance, bile acid diarrhoea, sugar intolerances, barrier dysfunction, microbiome, immune activation chemicals released latter mechanism. basic molecular contributing these pathophysiologies are increasingly recognised, offering opportunities intervene medications specifically food components, receptors potentially microbiome. Although supporting interventions each mechanism is not same level proof, current state-of-the-art provides opportunity advance practice from based on symptoms individualisation guided pathophysiology clinically identified biomarkers. Conclusion These advances augur well implementation evidence-based actionable biomarkers psychological disturbances.

Language: Английский

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Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications

Microorganisms, Journal Year: 2023, Volume and Issue: 11(10), P. 2369 - 2369

Published: Sept. 22, 2023

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, unclassified. Over past decade, role of gut microbiota IBS has garnered significant attention scientific community. Emerging research spotlights intricate involvement dysbiosis pathogenesis. Studies have demonstrated reduced microbial diversity stability specific alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal transplantation, even diet, offer exciting prospects managing IBS. However, definitive conclusions are hindered heterogeneity these studies. Further should focus on elucidating mechanisms, developing microbiome-based diagnostics, enabling personalized therapies tailored an individual’s microbiome profile. This review takes deep dive into microscopic world inhabiting our guts, its implications Our aim elucidate complex interplay between subtype, exploring novel microbiota-targeted treatments providing comprehensive overview current state knowledge.

Language: Английский

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New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics

Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 58(7), P. 605 - 621

Published: May 9, 2023

Abstract Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut–brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance. Recent advances proposed epigenetic factors as possible regulators several mechanisms involved in IBS pathophysiology. These include biomolecular inducing chromosome-related heritable changes gene expression regardless DNA coding sequence. Accordingly, altered gut may increase production metabolites such sodium butyrate, prominent inhibitor histone deacetylases. Patients with showed an increased amount butyrate-producing microbial phila well profile methylated genes micro-RNAs (miRNAs). Importantly, acetylation specific miRNA profiles are different be applied for future diagnostic purposes, especially to detect permeability visceromotor dysfunctions. In this review, we summarize current knowledge role epigenetics

Language: Английский

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The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 27, 2024

Obesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts immune signaling leading endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the barrier but also exert immunomodulatory effects via G protein-coupled receptor binding epigenetic regulation. are emerging as potential agents counteract dysbiosis-induced changes, specifically targeting genes through DNA methylation, histone acetylation, microRNAs (miRNAs), long non-coding RNAs (lncRNAs). To assess whether can effectively interrupt detrimental cascade obesity this review aims provide a comprehensive overview current evidence for their clinical application. The emphasizes factors influencing SCFA production, intricate connections between metabolism, system, microbiome, mechanisms regulated by that impact metabolism system.

Language: Английский

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