The protective role of conjunctival goblet cell mucin sialylation DOI Creative Commons

Moe Matsuzawa,

Tomoaki Ando, Saaya Fukase

et al.

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

Published: March 17, 2023

Abstract Gel-forming mucins secreted by conjunctival goblet cells have been implicated in the clearance of allergens, pathogens, and debris. However, their roles remain incompletely understood. Here we show that human mouse cell Alcian blue-detectable sialic acids, but not sulfates steady state. Interestingly, Balb/c strain lacks this sialylation due to a point mutation sialyltransferase gene, St6galnac1 , which is responsible for sialyl-Tn synthesis. Introduction intact restores mucus. Sialylated mucus efficiently captures encapsulates allergen particles an impenetrable layer, leading protection mice from development allergic conjunctivitis. Expression ST6GALNAC1 upregulated humans under conditions with chronic stimuli. These results indicate sialylated glycans on ocular play essential role maintaining mucosa protecting incoming foreign bodies such as particles.

Language: Английский

Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota DOI Open Access
William G. Fusco, Manuel Bernabeu, Marco Cintoni

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(9), P. 2211 - 2211

Published: May 6, 2023

Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis their deficiency is involved the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, cardiometabolic disorders. SCFAs are metabolites specific bacterial taxa human microbiota, production influenced by foods or food supplements, mainly prebiotics, direct fostering these taxa. This Review provides an overview SCFAs’ roles functions, SCFA-producing bacteria, from microbiological characteristics taxonomy to biochemical process that lead release SCFAs. Moreover, we will describe potential therapeutic approaches boost levels treat different related diseases.

Language: Английский

Citations

400
The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids DOI Creative Commons
Sandra Holmberg, R Feeney, V. K.

et al.

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

Published: April 25, 2024

Abstract Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the bacterial configuration disturbs this microbe-mucus interaction, but specific microbial metabolites responsible maintaining remain poorly understood. By using human-to-mouse microbiota transplantation ex vivo analysis of function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve capacity to prevent diet-mediated defects. Mucus growth, critical feature intact mucus, correlated with abundance commensal Blautia , supplementation coccoides mice confirmed mucus-stimulating capacity. Mechanistically, B. stimulated growth through production short-chain fatty acids propionate acetate via activation acid receptor Ffar2, which could serve new target restore during mucus-associated lifestyle diseases.

Language: Английский

Citations

45
Orchestration of MUC2 — The key regulatory target of gut barrier and homeostasis: A review DOI
Yaxin Liu, Zihan Yu, Lanping Zhu

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 236, P. 123862 - 123862

Published: March 2, 2023

Language: Английский

Citations

44
Rational Design of Orally Administered Cascade Nanozyme for Inflammatory Bowel Disease Therapy DOI Open Access
Yixin Yu,

Xianguang Zhao,

Xudong Xu

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(44)

Published: Aug. 23, 2023

Inflammatory bowel disease (IBD) affects millions of individuals worldwide annually. Enteric reactive oxygen species (ROS) play critical roles in the physiology and pathology IBD. Nanozymes hold great promise for treatment IBD because their exceptional ability to regulate redox homeostasis during ROS-related inflammation. However, rapid development orally administered, acid-tolerant, antioxidant nanozymes therapy is challenging. Here, a nine-tier high-throughput screening strategy established address multifaceted demands, including intrinsic stability, radioactivity, solubility, gut microbiome toxicity, biomimetic elements, intermediate frontier molecular orbitals, reaction energy barriers, negative charges, acid tolerance. Ni3 S4 selected as best matching material from 146 323 candidates, which exhibits superoxide dismutase-catalase bienzyme-like activity 3.13- 1.80-fold more active than natural enzymes. As demonstrated mouse model, stable gastrointestinal tract without toxicity specifically targets diseased colon alleviate oxidative stress. RNA 16S rRNA sequencing analyses show that effectively inhibits cellular pathways pro-inflammatory factors restores microbiota. This study not develops highly efficient administered cascade nanozyme offers next-generation paradigm rational design nanomedicine through data-driven approaches.

Language: Английский

Citations

44
Lac-Phe mediates the effects of metformin on food intake and body weight DOI
Shuke Xiao, Veronica L. Li,

Xuchao Lyu

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(4), P. 659 - 669

Published: March 18, 2024

Language: Английский

Citations

29
Epithelial‐immune cell crosstalk for intestinal barrier homeostasis DOI Creative Commons
Yikun Yao, Wanjing Shang, Lingyu Bao

et al.

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(6)

Published: March 31, 2024

Abstract The intestinal barrier is mainly formed by a monolayer of epithelial cells, which forms physical to protect the gut tissues from external insults and provides microenvironment for commensal bacteria colonize while ensuring immune tolerance. Moreover, various cells are known significantly contribute function either directly interacting with or producing mediators. Fulfilling this mucosal homeostasis requires not only intrinsic regulation (IECs) but also constant communication microbes. reciprocal interactions between IECs modulate integrity. Dysregulation could lead dysbiosis, inflammation, tumorigenesis. In overview, we provide an update on characteristics functions IECs, how they integrate their tissue microbiota establish homeostasis.

Language: Английский

Citations

22
ILC3s regulate the gut microbiota via host intestinal galactosylation to limit pathogen infection in mice DOI
Wenyan Wang, Na Li, Hongkai Xu

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

Citations

3
Human breast milk-derived exosomes and their positive role on neonatal intestinal health DOI

Gen Chen,

Xiangdong Ouyang,

Yue Mu

et al.

Pediatric Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Language: Английский

Citations

2
Mutant glycosidases for labeling sialoglycans with high specificity and affinity DOI Creative Commons
Yunfei Li, Qi Tang, Xiangqian Guo

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Affinity labeling of biomacromolecules is vital for bioimaging and functional studies. However, affinity probes recognizing glycans with high specificity remain scarce. Here we report the development glycan recombinant binders (GRABs) based on mutant bacterial sialidases, which are enzymatically inactive but preserve stringent sialoglycan substrates. By mutating a key catalytic residue Streptococcus pneumoniae neuraminidase A (SpNanA) Ruminococcus gnavus H (RgNanH), develop GRAB-Sia GRAB-Sia3 total sialoglycans α2,3-sialosides, respectively. The GRABs exhibit strict substrate linkage specificity, tetramerization streptavidin substantially increases their avidity. tetrameric (tetra-GRABs) effective tools probing in immunoblotting, flow cytometry, immunoprecipitation, fluorescence imaging. Furthermore, multiplex analysis tetra-GRABs uncovers spatially distinct various mouse organs. This work provides versatile toolkit analyzing sensitivity, convenience. Highly specific labels scarce, limiting use many applications. Here, authors sialidase mutants, sialoglycans.

Language: Английский

Citations

2
The role of intestinal stem cell within gut homeostasis: Focusing on its interplay with gut microbiota and the regulating pathways DOI Creative Commons

Haoming Luo,

Mingxing Li, Fang Wang

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(13), P. 5185 - 5206

Published: Jan. 1, 2022

Intestinal stem cells (ISCs) play an important role in maintaining intestinal homeostasis via promoting a healthy gut barrier. Within the cell niche, microbiota linking crosstalk of dietary influence and host response has been identified as key regulator ISCs. Emerging insights from recent research reveal that ISC interplay regulates epithelial self-renewal. This article reviews knowledge on their local environment (stem niche) associating with metabolites well signaling pathways. The current progress organoid culture is further summarized. Subsequently, challenges future directions are discussed.

Language: Английский

Citations

41