The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets DOI Creative Commons
Millicent N. Ekwudo, Carolina Gubert, Anthony J. Hannan

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Language: Английский

Bile acids and the gut microbiota: metabolic interactions and impacts on disease DOI
Stephanie L. Collins, Jonathan G. Stine, Jordan E. Bisanz

et al.

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 21(4), P. 236 - 247

Published: Oct. 17, 2022

Language: Английский

Citations

496
Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis DOI Creative Commons
Juanjuan Wang, Ningning Zhu, Lei Su

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 793 - 793

Published: March 2, 2023

The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to regulation of host immune response homeostasis. Alterations have been found in many immune-related diseases. metabolites generated by specific microorganisms such as short-chain fatty acids (SCFAs), tryptophan (Trp) bile acid (BA) metabolites, not only affect genetic epigenetic but also impact metabolism cells, immunosuppressive inflammatory cells. cells (such tolerogenic macrophages (tMacs), dendritic (tDCs), myeloid-derived suppressive (MDSCs), regulatory T (Tregs), B (Breg) innate lymphocytes (ILCs)) Macs (iMacs), DCs, CD4 helper (Th)1, CD4Th2, Th17, natural killer (NK) NK neutrophils) express different receptors for SCFAs, Trp BA from microorganisms. Activation these promotes differentiation function inhibits causing reprogramming local systemic system maintain homeostasis individuals. We here will summarize recent advances understanding effects on homeostasis, especially functions

Language: Английский

Citations

208
Microbiota-mediated colonization resistance: mechanisms and regulation DOI
Gustavo Caballero-Flores, Joseph M. Pickard, Gabriel Núñez

et al.

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 21(6), P. 347 - 360

Published: Dec. 20, 2022

Language: Английский

Citations

170
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia DOI Creative Commons
Emily Connell, Gwénaëlle Le Gall, Matthew G. Pontifex

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 17, 2022

A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.

Language: Английский

Citations

129
Metabolic Messengers: bile acids DOI
Alessia Perino, Kristina Schoonjans

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(4), P. 416 - 423

Published: March 25, 2022

Language: Английский

Citations

126
The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease DOI Creative Commons

John P. Thomas,

Dezső Módos,

Simon Rushbrook

et al.

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

Published: Feb. 3, 2022

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that arises due to complex interactions between host genetic risk factors, environmental and dysbiotic gut microbiota. Although metagenomic approaches have attempted characterise dysbiosis occurring in IBD, precise mechanistic pathways interlinking microbiota intestinal mucosa are still yet be unravelled. To deconvolute these interactions, more reductionist approach involving microbial metabolites has been suggested. Bile acids emerged as key class microbiota-associated perturbed IBD patients. In recent years, metabolomics studies revealed consistent defect bile acid metabolism with an increase primary reduction secondary This review explores evolving evidence specific interact epithelial immune cells contribute milieu seen IBD. Furthermore, we summarise linking intracellular known relevant including autophagy, apoptosis, inflammasome pathway. Finally, discuss how novel experimental bioinformatics could further advance our understanding role inform therapeutic strategies

Language: Английский

Citations

104
Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation DOI
Morgane M. Thibaut, Laure B. Bindels

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(3), P. 223 - 236

Published: Jan. 21, 2022

Language: Английский

Citations

102
A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers DOI
Marine Fidelle, Conrad Rauber, Carolina Alves Costa Silva

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6649)

Published: June 8, 2023

Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but mechanisms underlying their immunosuppressive effects remain unknown. By inducing down-regulation mucosal addressin adhesion molecule (MAdCAM-1) ileum, post-ABX gut recolonization by Enterocloster species drove emigration enterotropic α4β7+CD4+ regulatory T 17 cells into tumor. These deleterious ABX were mimicked oral gavage species, genetic deficiency, or antibody-mediated neutralization MAdCAM-1 and its receptor, α4β7 integrin. contrast, fecal microbiota transplantation interleukin-17A prevented ABX-induced immunosuppression. In independent lung, kidney, bladder patient cohorts, low serum levels soluble had a negative prognostic impact. Thus, MAdCAM-1-α4β7 axis constitutes an actionable immune checkpoint immunosurveillance.

Language: Английский

Citations

100
Interactive Relationships between Intestinal Flora and Bile Acids DOI Open Access

Xiaohua Guo,

Edozie Samuel Okpara,

Wanting Hu

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8343 - 8343

Published: July 28, 2022

The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans animals, particularly those involved maintenance intestinal homeostasis, immunity, inflammation, tumorigenesis. diversity bile acids a result joint efforts host microflora. There bidirectional relationship between community that, while flora tightly modulates metabolism synthesis acids, acid pool composition affect homeostasis flora. Homeostatic imbalances systems may lead to development variety diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), hepatocellular carcinoma (HCC), type 2 diabetes (T2DM), polycystic ovary syndrome (PCOS). interactions be (in)directly pathogenesis these diseases.

Language: Английский

Citations

96
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

91