Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions DOI Creative Commons
Gilda Varricchi, Remo Poto, Gianluca Ianiro

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 2, 2021

Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority CVID patients have polygenic inheritance. Immune dysfunction in can frequently involve gastrointestinal tract and lung. Few studies started to investigate gut microbiota profile patients. Overall, results suggest that there a reduction alpha beta diversity compared controls. In addition, these exhibit increased plasma lipopolysaccharide (LPS) markers (sCD14 sCD25) systemic immune cell activation. with enteropathy decreased IgA expression duodenal tissue. Mouse models for unsatisfactorily recapitulate causes human CVID. molecular pathways which contribute inflammation possibly tumorigenesis remain poorly understood. Several fundamental questions concerning relationships between development chronic inflammatory conditions, autoimmune disorders or cancer unanswered. Moreover, it unknown whether possible modify microbiome outcome through specific therapeutic interventions.

Language: Английский

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

Mengyao Yan,

Shuli Man,

Benyue Sun

et al.

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

Citations

86
Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis DOI
Jia Wang, Yitao Li, Kenneth Cheung

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 67(5), P. 865 - 878

Published: July 27, 2023

Language: Английский

Citations

67
Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy DOI Creative Commons
Bo Tang, Li Tang, Shengpeng Li

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 9, 2023

Abstract Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that characterized by increased serum bile acid and adverse fetal outcomes. The aetiology mechanism ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show the gut microbiome differed significantly between individuals with healthy pregnant women, colonization from patients was sufficient to induce in mice. microbiomes were primarily Bacteroides fragilis ( B. ), able promote inhibiting FXR signaling via its BSH activity modulate metabolism. -mediated inhibition responsible for excessive synthesis interrupted hepatic excretion ultimately initiation ICP. We propose modulation microbiota-bile acid-FXR axis may be value treatment.

Language: Английский

Citations

55
The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice DOI
Chuyu Yun, Sen Yan, Baoying Liao

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(5), P. 947 - 962

Published: May 20, 2024

Language: Английский

Citations

26
Gut-liver axis: Pathophysiological concepts and medical perspective in chronic liver diseases DOI Creative Commons
Susana Rodrigues, Van der Merwe, Aleksander Krag

et al.

Seminars in Immunology, Journal Year: 2024, Volume and Issue: 71, P. 101859 - 101859

Published: Jan. 21, 2024

Language: Английский

Citations

19
Role of bile acids in inflammatory liver diseases DOI Creative Commons
Ioannis Evangelakos, Jöerg Heeren,

Esther Verkade

et al.

Seminars in Immunopathology, Journal Year: 2021, Volume and Issue: 43(4), P. 577 - 590

Published: July 8, 2021

Abstract Bile acids and their signaling pathways are increasingly recognized as potential therapeutic targets for cholestatic metabolic liver diseases. This review summarizes new insights in bile acid physiology, focusing on regulatory roles of the control immune regulation effects pharmacological modulators human disease. Recent mouse studies have highlighted importance interactions between gut microbiome. Interfering with microbiome composition may be beneficial diseases by modulating formation secondary acids, different species functions. receptors such FXR, VDR, TGR5 expressed a variety cells involved innate well adaptive immunity, specific microbial metabolites positively modulate responses host. Identification Cyp2c70 enzyme responsible generation hydrophilic mouse/rat-specific muricholic has allowed murine models human-like composition. These novel will aid to accelerate translational research (patho)physiological .

Language: Английский

Citations

77
Bile acids contribute to the development of non-alcoholic steatohepatitis in mice DOI Creative Commons
Justine Gillard, Laure‐Alix Clerbaux, Maxime Nachit

et al.

JHEP Reports, Journal Year: 2021, Volume and Issue: 4(1), P. 100387 - 100387

Published: Oct. 14, 2021

Through FXR and TGR5 signaling, bile acids (BAs) modulate lipid glucose metabolism, inflammation fibrosis. Hence, BAs returning to the liver after enteric secretion, modification reabsorption may contribute pathogenesis of non-alcoholic steatohepatitis (NASH). Herein, we characterized enterohepatic profile signaling in preclinical models NASH, explored consequences experimental manipulation BA composition.We used high-fat diet (HFD)-fed foz/foz high-fructose western diet-fed C57BL/6J mice, compared them their respective controls. Mice received a supplemented with deoxycholic acid (DCA) composition.Compared controls, mice NASH had lower concentrations portal blood bile, while systemic were not significantly altered. Notably, secondary BAs, especially DCA, ratio primary strikingly NASH. was poor ligands, conferred anti-inflammatory protection Enhanced synthesis conversion livers contributed depletion BAs. Dietary DCA supplementation HFD-fed restored blood, increased improved dysmetabolic status, protected from steatosis hepatocellular ballooning, reduced macrophage infiltration.BA composition cycle, but circulation, is profoundly altered specific correction supporting role for NASH.This study clearly demonstrates that alterations development relevant models. Indeed, modulation perturbed prevented associated metabolic disorders.

Language: Английский

Citations

72
Bile Acids Activated Receptors in Inflammatory Bowel Disease DOI Creative Commons
Michele Biagioli, Silvia Marchianò, Adriana Carino

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1281 - 1281

Published: May 21, 2021

Once known exclusively for their role in nutrients absorption, bile acids have emerged as signaling molecules, generated from cholesterol breakdown, acting on several immune cells by activating a variety of receptors including the G protein-coupled acid receptor 1 (GPABR1 or TGR5), Farnesoid-X-receptor (FXR) and, recently discovered, retinoid-related orphan (ROR)γt. GPBAR1, FXR, and RORγt are highly expressed innate adaptive system (i.e., dendritic (DCs), macrophages, lymphoid 3 (ILC3s), T helper 17 (Th17) lymphocytes) plays an important regulating intestinal liver immunity, highlighting various species responses to microbial antigens. While primary breakdown secondary acids, GPBAR1 ligands, oxo-bile derivatives, microbiota, potential these mediating chemical communication between microbiota host. Changes dysbiosis, alter composition pool, promoting activation development chronic inflammation. In this review, we focus molecular mechanisms which altered promotes

Language: Английский

Citations

66
Recent advances on FXR-targeting therapeutics DOI Creative Commons

Katrin Panzitt,

Gernot Zollner, Hanns‐Ulrich Marschall

et al.

Molecular and Cellular Endocrinology, Journal Year: 2022, Volume and Issue: 552, P. 111678 - 111678

Published: May 20, 2022

The bile acid receptor FXR has emerged as a bona fide drug target for chronic cholestatic and metabolic liver diseases, ahead of all non-alcoholic fatty disease (NAFLD). is highly expressed in the intestine activation at both sites differentially contributes to its desired effects. Unrestricted activation, however, also comes along with undesired effects such pro-atherogenic lipid profile, pruritus hepatocellular toxicity under certain conditions. Several pre-clinical studies have confirmed potency but overall it remains still open whether selective intestinal advantageous over pan-FXR restricted or modulated can limit some side Even more, antagonist bear potential intestinal-selective drugs NAFLD models. In this review we will discuss molecular prerequisites in/activation from therapeutic point view, different steroidal non-steroidal agonists, ways restrict finally what learned models clinical trials therapeutics.

Language: Английский

Citations

52
Bile acids and their receptors in regulation of gut health and diseases DOI Creative Commons
Sen Lin, Sutian Wang, Peng Wang

et al.

Progress in Lipid Research, Journal Year: 2022, Volume and Issue: 89, P. 101210 - 101210

Published: Dec. 25, 2022

Language: Английский

Citations

50