Short-chain fatty acids: linking diet, the microbiome and immunity

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(8), P. 577 - 595

Published: April 2, 2024

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

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

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Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2275 - 2275

Published: May 11, 2023

Background and objective: Inflammatory bowel disease (IBD), including Crohn’s ulcerative colitis, is a chronic inflammatory disorder characterized by aberrant immune responses compromised barrier function in the gastrointestinal tract. IBD associated with altered gut microbiota their metabolites colon. Butyrate, microbial metabolite, plays crucial role regulating function, epithelial intestinal homeostasis. In this review, we aim to present an overview of butyrate synthesis metabolism mechanism action maintaining homeostasis discuss therapeutic implications IBD. Methods: We searched literature up March 2023 through PubMed, Web Science, other sources using search terms such as butyrate, inflammation, IBD, disease, colitis. Clinical studies patients preclinical rodent models were included summary butyrate. Results: Research last two decades has shown beneficial effects on function. Most clinical have positive effect oral supplements reducing inflammation remission colitis animal patients. However, enema showed mixed effects. Butyrogenic diets, germinated barley foodstuff oat bran, are found increase fecal concentrations reduce activity index both Conclusions: The current suggests that potential add-on therapy maintain remission. Further needed determine if administration alone effective treatment for

Language: Английский

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An Engineered Butyrate-Derived Polymer Nanoplatform as a Mucosa-Healing Enhancer Potentiates the Therapeutic Effect of Magnolol in Inflammatory Bowel Disease

ACS Nano, Journal Year: 2023, Volume and Issue: 18(1), P. 229 - 244

Published: Dec. 19, 2023

Colonic epithelial damage and dysregulated immune response are crucial factors in the progression exacerbation of inflammatory bowel disease (IBD). Nanoenabled targeted drug delivery to inflamed intestinal mucosa has shown promise inducing maintaining colitis remission, while minimizing side effects. Inspired by excellent antioxidative anti-inflammatory efficacy naturally derived magnolol (Mag) gut homeostasis regulation microbiota-derived butyrate, we developed a pH/redox dual-responsive butyrate-rich polymer nanoparticle (PSBA) as an oral Mag system for combinational therapy IBD. PSBA showed high butyrate content 22% effectively encapsulated Mag. The Mag-loaded nanoparticles (PSBA@Mag) demonstrated colonic pH reduction-responsive release, ensuring efficient retention adhesion colon mice. PSBA@Mag not only normalized level reactive oxygen species effectors but also restored barrier function both ulcerative Crohn's mouse models. Importantly, promoted migration healing ability cells vitro vivo, sensitizing therapeutic animal Moreover, transcriptomics metabolism analyses revealed that mitigated inflammation suppressing production pro-inflammatory cytokines chemokines restoring lipid metabolism. Additionally, this nanomedicine modulated microbiota inhibiting pathogenic Proteus Escherichia-Shigella promoting proliferation beneficial probiotics, including Lachnoclostridium, Lachnospiraceae_NK4A136_group norank_f_Ruminococcaceae. Overall, our findings highlight potential butyrate-functionalized polymethacrylates versatile effective nanoplatforms repair combating IBD other gastrointestinal disorders.

Language: Английский

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Strategies for the development of metalloimmunotherapies

Nature Biomedical Engineering, Journal Year: 2024, Volume and Issue: 8(9), P. 1073 - 1091

Published: June 24, 2024

Language: Английский

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A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel‐Based Multistage NO Delivery Microcapsules

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 7, 2024

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, removal reactive intestinal oxygen species, and regulation flora. However, owing complex structure gastrointestinal tract influence mucus, current small-molecule biologic-based drugs for colitis cannot effectively act at site colon inflammation, as a result, they tend exhibit low efficacies toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed achieve release inflammation by targeting tissues using nanogel. Surprisingly, oral administration suppresses growth pathogenic bacteria increases abundance probiotic bacteria. Metabolomics further show that an increased probiotics promotes production metabolites, including short-chain fatty acids indole derivatives, which modulate immunity restore barrier via interleukin-17 PI3K-Akt signaling pathways. This work reveals gas therapy strategy based modulates microbial balance, thereby reducing promoting repair, ultimately providing new therapeutic approach clinical management colitis.

Language: Английский

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Nanoodor Particles Deliver Drugs to Central Nervous System via Olfactory Pathway

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Central nervous system (CNS) disorders confront significant challenges in drug delivery due to the blood-brain barrier (BBB). Inspired by rapid and precise binding of odor molecules olfactory receptors (ORs), this research uses thiolated HPMA construct nanoparticles (nanoodors) capable delivering drugs CNS via olfacto-cerebral pathway overcome obstruction. The nanoodor core is used encapsulate agomelatine (AGO), a CNS-targeting antidepressant, encapsulation efficiency exceeded 80%. A series thiol-presenting nanoscale structures with different surface densities thiol groups are constructed, effectiveness positively correlated density on their surface. Notably, nanoodors enable brain-targeted delivery, outperforming commercially available oral formulations terms accumulation brain antidepressant effects. study transport action mechanisms revealed that after ORs, rapidly delivered pathway. Nanoodors, first design deliver mimicking natural smells for treatment disorders, expected achieve clinical transformation, benefiting human health.

Language: Английский

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Adoptive T _reg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome

Science Advances, Journal Year: 2023, Volume and Issue: 9(20)

Published: May 17, 2023

Regulatory T (Treg) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting accumulation for localized diseases. Besides, the instability plasticity Treg also induce phenotype transition functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) favorable mechanical performance spacious encapsulation cavity to support survival, as well tunable channels facilitate migration local therapy psoriasis. In addition, enzyme-degradable matrix could release fatty acid in hyperinflammatory area psoriasis, enhancing suppressive functions via oxidation (FAO)-mediated metabolic intervention. administered through PMN substantially ameliorated psoriasis syndrome assistance acid-mediated intervention mouse model. This tailorable offer transformative platform treat variety

Language: Английский

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Oral Nanomedicine: Challenges and Opportunities

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(6)

Published: Sept. 19, 2023

Abstract Compared to injection administration, oral administration is free of discomfort, wound infection, and complications has a higher compliance rate for patients with diverse diseases. However, reduces the bioavailability medicines, especially biologics (e.g., peptides, proteins, antibodies), due harsh gastrointestinal biological barriers. In this context, development prosperity nanotechnology have helped improve bioactivity availability medicines. On basis, first, barriers are discussed, then nanomedicine based on organic inorganic nanomaterials their biomedical applications in diseases reviewed. Finally, challenges potential opportunities future nanomedicine, which may provide vital reference eventual clinical transformation standardized production put forward.

Language: Английский

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The Impact of Gut Microbiota-Derived Metabolites on the Tumor Immune Microenvironment

Cancers, Journal Year: 2023, Volume and Issue: 15(5), P. 1588 - 1588

Published: March 3, 2023

Prevention of the effectiveness anti-tumor immune responses is one canonical cancer hallmarks. The competition for crucial nutrients within tumor microenvironment (TME) between cells and creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better dynamic interactions surrounding cells. Paradoxically, both activated T are metabolically dependent on glycolysis, even in presence oxygen, process known as Warburg effect. intestinal microbial community delivers various types small molecules that can potentially augment functional capabilities host system. Currently, several studies trying explore relationship metabolites secreted human microbiome immunity. Recently, it has shown diverse array commensal bacteria synthetizes bioactive enhance efficacy immunotherapy, including checkpoint inhibitor (ICI) treatment adoptive cell therapy with chimeric antigen receptor (CAR) In this review, we highlight importance bacteria, particularly gut microbiota-derived capable shaping metabolic, transcriptional epigenetic processes TME therapeutically meaningful way.

Language: Английский

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