Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients

Allergy, Journal Year: 2023, Volume and Issue: 79(2), P. 353 - 383

Published: Dec. 12, 2023

Abstract Nutritional Immunity is one of the most ancient innate immune responses, during which body can restrict nutrients availability to pathogens and restricts their uptake by gut mucosa (mucosal block). Though this be a beneficial strategy infection, it also associated with non‐communicable diseases—where pathogen missing; leading increased morbidity mortality as micronutritional distribution in hindered. Here, we discuss acute response respect nutrients, opposing nutritional demands regulatory inflammatory cells particularly focus on some linked inflammation such iron, vitamins A, Bs, C, other antioxidants. We propose that while absorption certain micronutrients hindered inflammation, dietary lymph path remains available. As such, several clinical trials investigated role lymphatic system protein absorption, following ketogenic diet an intake antioxidants, vitamins, minerals, reducing ameliorating disease.

Language: Английский

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Microbiota-derived metabolites in inflammatory bowel disease

Seminars in Immunopathology, Journal Year: 2025, Volume and Issue: 47(1)

Published: March 4, 2025

Abstract Understanding the role of gut microbiota in pathogenesis inflammatory bowel diseases (IBD) has been an area intense research over past decades. Patients with IBD exhibit alterations their microbial composition compared to healthy controls. However, studies focusing solely on taxonomic analyses have struggled deliver replicable findings across cohorts regarding which species drive distinct patterns IBD. The focus therefore shifted studying functionality microbes, especially by investigating effector molecules involved immunomodulatory functions microbiota, namely metabolites. Metabolic profiles are altered IBD, and several metabolites shown play a causative shaping immune animal models. Therefore, understanding complex communication between metabolites, host bears great potential unlock new biomarkers for diagnosis, disease course therapy response as well novel therapeutic options treatment In this review, we primarily promising classes thought exert beneficial effects generally decreased Though results from human trials promising, they not so far provided large-scale break-through IBD-therapy improvement. We propose tailored personalized supplementation based multi-omics analysis accounts individual metabolic patients rather than one-size-fits-all approaches.

Language: Английский

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Hydrogen Sulfide and Gut Microbiota: Their Synergistic Role in Modulating Sirtuin Activity and Potential Therapeutic Implications for Neurodegenerative Diseases

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1480 - 1480

Published: Nov. 4, 2024

The intricate relationship between hydrogen sulfide (H2S), gut microbiota, and sirtuins (SIRTs) can be seen as a paradigm axis in maintaining cellular homeostasis, modulating oxidative stress, promoting mitochondrial health, which together play pivotal role aging neurodegenerative diseases. H2S, gasotransmitter synthesized endogenously by specific acts potent modulator of function protecting against damage. Through sulfate-reducing bacteria, microbiota influences systemic H2S levels, creating link health metabolic processes. Dysbiosis, or an imbalance microbial populations, alter production, impair function, increase heighten inflammation, all contributing factors diseases such Alzheimer’s Parkinson’s. Sirtuins, particularly SIRT1 SIRT3, are NAD+-dependent deacetylases that regulate biogenesis, antioxidant defense, inflammation. enhances sirtuin activity through post-translational modifications, sulfhydration, activate pathways essential for mitigating damage, reducing longevity. SIRT1, example, deacetylates NF-κB, pro-inflammatory cytokine expression, while SIRT3 modulates key enzymes to improve energy metabolism detoxify reactive oxygen species (ROS). This synergy is profoundly influenced the levels and, turn, impacts activation. microbiota–H2S–sirtuin also regulating neuroinflammation, plays central pathogenesis Pharmacological interventions, including donors sirtuin-activating compounds (STACs), promise these synergistically, providing novel therapeutic approach conditions. suggests diversity optimal have far-reaching effects on brain health.

Language: Английский

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Explainable AI-prioritized plasma and fecal metabolites in inflammatory bowel disease and their dietary associations

iScience, Journal Year: 2024, Volume and Issue: 27(7), P. 110298 - 110298

Published: June 18, 2024

Fecal metabolites effectively discriminate inflammatory bowel disease (IBD) and show differential associations with diet. Metabolomics AI-based models, including explainable AI (XAI), play crucial roles in understanding IBD. Using datasets from the UK Biobank Human Microbiome Project Phase II IBD Multi'omics Database (HMP2 IBDMDB), this study uses multiple machine learning (ML) classifiers Shapley additive explanations (SHAP)-based XAI to prioritize plasma fecal analyze their diet correlations. Key findings include identification of discriminative like glycoprotein acetyl albumin plasma, as well nicotinic acid andurobilin feces. provided a more robust predictor model (AUC [95%]: 0.93 [0.87-0.99]) compared 0.74 [0.69-0.79]), stronger group-differential diet-metabolite The validates known metabolite highlights impact on interplay between gut microbial

Language: Английский

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Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

Attention Deficit Hyperactivity Disorder (ADHD) is a clinically common neurodevelopmental disorder of the brain. In addition to genetic factors, an imbalance in gut flora may also play role development ADHD. Currently, it critical investigate function and related metabolites, which form fundamental basis bidirectional cross-linking between brain gut, focusing on changed This study aimed possible relationship changes metabolites ADHD by analyzing metagenome untargeted metabolomics fecal samples from patients. Specifically, we attempted identify key metabolic pathways they are involved in, as well analyze detail structure composition order further symptoms, some behavioral studies were conducted following transplantation patients into rats. The results analysis revealed several distinct strains, including Bacteroides cellulosilyticus , could be important for diagnosing Additionally, group showed modifications nicotinamide nicotinic acid metabolite this pathway. demonstrated that rats with transplants displayed increased locomotor activity interest, indicating onset behaviors such facilitated associated research verified alterations metabolism observed provided list significantly altered Simultaneously, our findings microbiome potentially trigger animals, providing experimental comprehending influence These might provide new perspectives novel treatment strategies.

Language: Английский

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Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 7, 2023

Introduction We have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor–gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to pathogenesis inflammatory bowel disease (IBD). However, mechanism underlying PGC1α expression and activity during IBD is not yet clear. Methods Mice (male; C57Bl/6, Villincre /+; Pgc1afl/fl mice, ) were subjected experimental colitis treated with nicotinamide riboside. Western blot, high-resolution respirometry, adenine dinucleotide (NAD+) quantification, immunoprecipitation used in this study. Results demonstrate significant depletion NAD+ levels mice undergoing colitis, as well humans ulcerative colitis. While we found no decrease NAD+-synthesizing enzymes did find an increase mRNA level, enzymatic activity, NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment precursor reduced severity restored mitochondrial function, increased active levels; however, repletion benefit transgenic lack epithelium, suggesting therapeutic effects require intact axis. Discussion Our results emphasize importance both health homeostasis suggest novel approach for management. These findings also provide mechanistic basis clinical trials riboside patients.

Language: Английский

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Game changer: Navigating between challenges and hopes in geropharmacology

Advances in pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Probiotic characteristics and whole genome sequencing of Pediococcus pentosaceus SNF15 and its protective effect on mice diarrhea induced by Escherichia coli K99

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: March 13, 2025

Escherichia coli ( E. col iK99) is one of the primary pathogens that cause infectious calf diarrhea, resulting in mortality and causing economic losses. Probiotics have been widely researched for their positive impact on inhibiting growth pathogenic bacteria enhancing immunity gut health as alternatives to antibiotics. This study isolated probiotic from healthy feces: Pediococcus pentosaceus SNF15 P. SNF15). In vitro assessments included character acid-producing ability, bile salt artificial gastroenteric fluid tolerance, Caco-2 adhesion, hemolysis screening, antibiotic susceptibility. Whole-genome sequencing identified immunomodulatory, antimicrobial, metabolic genes. A murine model evaluated efficacy against K99, outcomes clinical indices (fecal score, weight), histopathology (H&E), inflammatarty factor (qRT-PCR ELISA), tight junction proteins mucin (immunohistochemistry detection). Finally, 16S rRNA was performed compare composition relative abundance microbiota among different groups. demonstrated excellent performance acid production capacity, resistance, cells adhesion safety (γ-hemolysis, sensitivity) Genomic analysis revealed immune, anti-inflammatory, antagonistic pathogens, carbohydrate utilization, including secondary acid, nicotinate nicotinamide. The animal tests showed treatment protects K99 infection, evidenced by symptoms, weight loss, fecal liver atrophy, spleen enlargement occurred histological damage. Compared with CN group, supplementation strains ameliorated damage jejunum content occludin, claudin, ZO-1, MUC2 decreased levels IL-6, IL-1β, TNF-α jejunum. rDNA sequence results infection led an imbalance microbiota; proportion Firmicutes Bacteroidetes decreased, Proteobacteria increased. helps improve intestinal microbial prevents this trend. can prevent treat epithelial mucosal integrity, permeability, immune-related cytokines regulate K99-infected mice. research possesses desirable characteristics could be used a potential remit neonatal caused infection.

Language: Английский

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Bacteroides fragilis-derived nicotinamide riboside attenuates radiation-induced intestinal injury by suppressing Gasdermin E-mediated pyroptosis in intestinal epithelial cells

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Introduction: IR (IR) is a common complication in patients with colorectal cancer (CRC) after radiotherapy. Currently, the search for effective treatments has become an urgent priority. Nicotinamide riboside (NR), precursor of vitamin B3 derivative and NAD (+), was enriched treatment commensal Bacteroides fragilis, suggesting that NR may perform protective role. However, specific role remains unclear. In this study, we investigated therapeutic effects on IR. Methods: C57BL/6J, Gsdme^ΔIEC (lacking GSDME intestinal epithelial cells, IECs), wild-type littermates were treated abdominal radiation exposure at 10Gy. The crypt-derived organoids cell lines FHC, NCM460, IEC-6 irradiated or without administration SIRT1 inhibitor EX527 under stimulation. A series assays subsequently carried out to explore effects, degree IECs repair, underlying mechanism. Results: significantly ameliorated mice, as evidenced by reduced weight loss, shortened colonic length, improved histological associated index, restored flora, which increased relative abundance Muribaculaceae, decreased Escherichia_coli. Additionally, goblet density, crypt promoted Ki-67 ZO-1 expression, reactive oxygen species (ROS) levels, maintained mitochondrial morphology IECs. Mechanistically, activated inhibited gasdermin E (GSDME)-induced pyroptosis. Further investigations using experimental mouse model IECs) revealed barrier repair through inhibition SIRT1-dependent manner. Compared those healthy controls, level radiation-injured mucosa from CRC radiotherapy downregulation SIRT1, Ki-67, ZO-1. Conclusion: Our study demonstrated mitigates inhibiting GSDME-mediated pyroptosis restoring homeostasis. These findings suggest could serve promising strategy following

Language: Английский

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Intestinal lysozyme1 deficiency alters microbiota composition and impacts host metabolism through the emergence of NAD ⁺ -secreting ASTB Qing110 bacteria

mSystems, Journal Year: 2024, Volume and Issue: 9(3)

Published: Feb. 16, 2024

The intestine plays a pivotal role in nutrient absorption and host defense against pathogens, orchestrated part by antimicrobial peptides secreted Paneth cells. Among these peptides, lysozyme has multifaceted functions beyond its bactericidal activity. Here, we uncover the intricate relationship between intestinal lysozyme, gut microbiota, metabolism. Lysozyme deficiency mice led to altered body weight, energy expenditure, substrate utilization, particularly on high-fat diet. Interestingly, metabolic benefits were linked changes microbiota composition. Cohousing experiments revealed that effects of microbiota-dependent. 16S rDNA sequencing highlighted differences microbial communities, with

Language: Английский

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