A serine-conjugated butyrate prodrug with high oral bioavailability suppresses autoimmune arthritis and neuroinflammation in mice DOI Creative Commons
Shijie Cao, Erica Budina, Michal M. Raczy

et al.

Nature Biomedical Engineering, Journal Year: 2024, Volume and Issue: 8(5), P. 611 - 627

Published: April 1, 2024

Butyrate-a metabolite produced by commensal bacteria-has been extensively studied for its immunomodulatory effects on immune cells, including regulatory T macrophages and dendritic cells. However, the development of butyrate as a drug has hindered butyrate's poor oral bioavailability, owing to rapid metabolism in gut, low potency (hence, necessitating high dosing), foul smell taste. Here we report that bioavailability can be increased esterifying it serine, an amino acid transporter aids escape resulting odourless tasteless prodrug (O-butyryl-L-serine, which named SerBut) from enhancing systemic uptake. In mice with collagen-antibody-induced arthritis (a model rheumatoid arthritis) experimental autoimmune encephalomyelitis multiple sclerosis), show SerBut substantially ameliorated disease severity, modulated key cell populations systemically disease-associated tissues, reduced inflammatory responses without compromising global response vaccination. may become promising therapeutic diseases.

Language: Английский

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

274
mRNA vaccines in disease prevention and treatment DOI Creative Commons
Gang Zhang, Tianyu Tang, Yinfeng Chen

et al.

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

Published: Sept. 20, 2023

Abstract mRNA vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases, thanks largely although not totally to their extraordinary performance recent years against worldwide plague COVID-19. The huge superiority regarding efficacy, safety, large-scale manufacture encourages pharmaceutical industries biotechnology companies expand application a diverse array despite nonnegligible problems design, fabrication, mode administration. This review delves into technical underpinnings vaccines, covering synthesis, delivery, adjuvant technologies. Moreover, this presents systematic retrospective analysis logical well-organized manner, shedding light on representative employed various diseases. scope extends across infectious cancers, immunological tissue damages, rare showcasing versatility potential therapeutic areas. Furthermore, engages prospective discussion current challenge direction for advancement utilization vaccines. Overall, comprehensive serves valuable resource researchers, clinicians, industry professionals, providing understanding aspects, historical context, future prospects fight

Language: Английский

Citations

114
γδ T cells: origin and fate, subsets, diseases and immunotherapy DOI Creative Commons
Yi Hu,

Qinglin Hu,

Yongsheng Li

et al.

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

Published: Nov. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Language: Английский

Citations

114
Gut microbiota and hypertension: association, mechanisms and treatment DOI Creative Commons
Zhihua Yang, Qingchun Wang,

Yangxi Liu

et al.

Clinical and Experimental Hypertension, Journal Year: 2023, Volume and Issue: 45(1)

Published: March 30, 2023

Objectives Hypertension is one of the most important risk factors for cardio-cerebral vascular diseases, which brings a heavy economic burden to society and becomes major public health problem. At present, pathogenesis hypertension unclear. Increasing evidence has proven that closely related dysbiosis gut microbiota. We briefly reviewed relevant literature on microbiota summarize relationship between hypertension, linked antihypertension effects drugs with their modulation microbiota, discussed potential mechanisms various microbes active metabolites alleviate thus providing new research ideas development drugs.Methods The was collected systematically from scientific database, including Elsevier, PubMed, Web Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well other sources, such classic books herbal medicine.Results can lead imbalance barrier dysfunction, increased harmful bacteria hydrogen sulfide lipopolysaccharide, decreased beneficial short-chain fatty acids, intestinal tight junction proteins permeability. Gut occurrence hypertension. main methods regulate include fecal transplantation, supplementation probiotics, antibiotics, diet exercise, antihypertensive drugs, natural medicines.Conclusions Investigating correlation may help reveal perspective great significance prevention treatment

Language: Английский

Citations

87
Fecal microbiota transplantation: Emerging applications in autoimmune diseases DOI Creative Commons

Ruixue Yang,

Zhenzhen Chen,

Jun Cai

et al.

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 141, P. 103038 - 103038

Published: April 26, 2023

Both genetic susceptibility and environmental factors are important contributors to autoimmune disease pathogenesis. As an factor, the gut microbiome plays a crucial role in development progression of diseases. Thus, strategies targeting alterations can potentially be used treat disease. Microbiota-based interventions, such as prebiotics, probiotics, dietary fecal microbiota transplantation (FMT), have attracted growing interest novel treatment approaches. FMT is effective method for treating recurrent Clostridioides difficile infections; moreover, it emerging promising patients with inflammatory bowel other Although mechanisms underpinning interaction between host not fully understood disease, has been shown restore altered composition, rebuild intestinal microecosystem, mediate innate adaptive immune responses achieve therapeutic effect. In this review, we provide overview discuss how approach Furthermore, recent challenges offer future research directions.

Language: Английский

Citations

52
Fungal microbiota sustains lasting immune activation of neutrophils and their progenitors in severe COVID-19 DOI
Takato Kusakabe, Woan-Yu Lin, Jin‐Gyu Cheong

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(11), P. 1879 - 1889

Published: Oct. 23, 2023

Language: Английский

Citations

46
Gut-Microbiota, and Multiple Sclerosis: Background, Evidence, and Perspectives DOI Open Access
Clelia Altieri, Barbara Speranza, Maria Rosaria Corbo

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(4), P. 942 - 942

Published: Feb. 14, 2023

Many scientific studies reveal a significant connection between human intestinal microbiota, eating habits, and the development of chronic-degenerative diseases; therefore, alterations in composition function microbiota may be accompanied by different chronic inflammatory mechanisms. Multiple sclerosis (MS) is an demyelinating disease central nervous system (CNS), which autoreactive immune cells attack myelin sheaths neurons. The purpose this paper was to describe main changes that occur gut MS patients, with focus on both its implications for health disease, as well variables influence it. Another point stressed role triggering factor modulate responses innate adaptive systems, intestine brain. In addition, comprehensive overview taxa modified presented, some points modulation therapeutic approach MS. Finally, significance gastro-intestinal pains (indirectly related dysbiosis) assessed using case study (questionnaire patients), willingness patients probiotics.

Language: Английский

Citations

43
Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis DOI Creative Commons
Mairead K. Heavey,

Anthony Hazelton,

Yuyan Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 6, 2024

Abstract Probiotic and engineered microbe-based therapeutics are an emerging class of pharmaceutical agents. They represent a promising strategy for treating various chronic inflammatory conditions by interacting with the host immune system and/or delivering therapeutic molecules. Here, we targeted probiotic yeast platform wherein Saccharomyces boulardii is designed to bind abundant extracellular matrix proteins found within lesions gastrointestinal tract through tunable antibody surface display. This approach enabled additional 24–48 h gut residence time compared controls 100-fold increased concentrations colon in preclinical models ulcerative colitis female mice. As result, pharmacodynamic parameters including length, colonic cytokine expression profiles, histological inflammation scores were robustly improved restored back healthy levels. Overall, these studies highlight potential microbial as oral dosage form treatment bowel diseases.

Language: Английский

Citations

31
A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation DOI Creative Commons

Ziqi Ma,

Tao Zuo, Norbert Frey

et al.

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

Published: Sept. 23, 2024

Language: Английский

Citations

26
Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility DOI

Mathis Wolter,

Erica T. Grant, Marie Boudaud

et al.

Molecular Systems Biology, Journal Year: 2024, Volume and Issue: 20(6), P. 596 - 625

Published: May 14, 2024

Language: Английский

Citations

24