Enhanced mucosal mitochondrial function corrects dysbiosis and OXPHOS metabolism in IBD DOI Open Access

Neeraj Kapur,

M. Ashfaqul Alam,

Syed Adeel Hassan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 14, 2024

ABSTRACT Background Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases delivery to the microbiome. Increased enteric promotes blooms of facultative anaerobes (eg. Proteobacteria ) restricts obligate Firmicutes ). Dysbiotic metabolites negatively affect host metabolism immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis corrects dysbiosis humanized Il10-/- mice. We posit that AuPhos IBD-associated dysbiotic metabolism. Methods Primary effect on Mito respiration healing process was studied ex vivo treated human colonic biopsies piroxicam-accelerated (Px) Secondary microbiome tested DSS-colitis WT B6 germ-free 129.SvEv or mice reconstituted with stool (Hu- Mice were orally (10- 25- mg/kg; q3d) vehicle, samples collected for fecal lipocalin-2 (f-LCN2) assay analyses using 16S rRNA sequencing. microbial determined untargeted global metabolomics. AuPhos-induced hypoxia IECs assessed by Hypoxyprobe-1 staining sections from pimonidazole HCl-infused DSS-mice. Effect oxygenation E. coli Nissle 1917 (aerobic respiration-proficient) cytochrome oxidase (cydA) mutant respiration-deficient). Results Metagenomic (16S) analysis revealed reduced relative abundances increased uninflamed WT, DSS-colitis, Hu-WT Hu- also hypoxyprobe-1 surface suggesting enhanced utilization. anaerobiosis confirmed a significant increase cydA compared (O2-utlizing) E.coli . Ex treatment showed mass, complexes I IV. Further, gene expression AuPhos-treated stem markers (Lgr4, Lgr5, Lrig1), concomitant decreases pro-inflammatory (IL1β,MCP1, RankL). Histological investigation AuPhos-fed Px- significantly decreased score mice, decrease mRNA cytokines ( ND5 , ATP6 altered associated SCFA synthesis, FAO, TCA cycle, tryptophan polyamine biosynthesis pathways. pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate succinate, an upregulation pyruvate glutarate pathways butyrate production. primary bile acids (BA) secondary BA (SBA). acylcarnitines L-carnitine reflective FAO. cycle intermediates creatine, energy reservoir substrates indicating OxPHOS. Besides, metabolism, Kynurenine its derivatives, pathway (Putresceine Spermine). Conclusion These findings indicate AuPhos-enhanced IEC mitochondrial function delivery, which disease-associated metabolomics restoring short-chain fatty acids, SBA, AA Graphical abstract

Язык: Английский

Gut dysbiosis: Ecological causes and causative effects on human disease DOI Creative Commons
Sebastian Winter, Andreas J. Bäumler

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(50)

Опубликована: Дек. 4, 2023

The gut microbiota plays a role in many human diseases, but high-throughput sequence analysis does not provide straightforward path for defining healthy microbial communities. Therefore, understanding mechanisms that drive compositional changes during disease (gut dysbiosis) continues to be central goal microbiome research. Insights from the pathogenesis field show an ecological cause dysbiosis is increased availability of host-derived respiratory electron acceptors, which are dominant drivers community composition. Similar host environment also several chronic illnesses, and better underlying informs approaches causatively link exacerbation symptoms. emerging picture suggests homeostasis maintained by functions control resources governing growth. Defining as weakening these directs attention identifies potential targets therapeutic intervention.

Язык: Английский

Процитировано

45

Recent advances in the epithelial barrier theory DOI Creative Commons
Yağız Pat, Duygu Yazıcı, Paolo D’Avino

и другие.

International Immunology, Год журнала: 2024, Номер 36(5), С. 211 - 222

Опубликована: Янв. 16, 2024

Abstract The epithelial barrier theory links the recent rise in chronic non-communicable diseases, notably autoimmune and allergic disorders, to environmental agents disrupting barrier. Global pollution toxic agent exposure have worsened over six decades because of uncontrolled growth, modernization, industrialization, affecting human health. Introducing new chemicals without any reasonable control their health effects through these years has led documented adverse effects, especially on skin mucosal barriers. These substances, such as particulate matter, detergents, surfactants, food emulsifiers, micro- nano-plastics, diesel exhaust, cigarette smoke, ozone, been shown compromise integrity. This disruption is linked opening tight-junction barriers, inflammation, cell death, oxidative stress, metabolic regulation. Consideration must be given interplay underlying inflammatory medications, affected tissues. review article discusses detrimental effect barrier-damaging compounds involves cellular molecular mechanisms.

Язык: Английский

Процитировано

23

Mitochondrial function and gastrointestinal diseases DOI

Parsa Haque,

Neeraj Kapur,

Terrence A. Barrett

и другие.

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2024, Номер 21(8), С. 537 - 555

Опубликована: Май 13, 2024

Язык: Английский

Процитировано

23

Type 2 immunity in allergic diseases DOI Creative Commons
İsmail Öğülür, Yasutaka Mitamura,

Duygu Yazıcı

и другие.

Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Язык: Английский

Процитировано

15

Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease DOI
Rafael Valdés‐Mas, Avner Leshem,

Danping Zheng

и другие.

Cell, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

7

Butyrate’s (a short-chain fatty acid) microbial synthesis, absorption, and preventive roles against colorectal and lung cancer DOI
Md Rezaul Karim, Safia Iqbal, Shahnawaz Mohammad

и другие.

Archives of Microbiology, Год журнала: 2024, Номер 206(4)

Опубликована: Март 4, 2024

Язык: Английский

Процитировано

16

Gastro-Intestinal Microbiota in Equines and Its Role in Health and Disease: The Black Box Opens DOI Creative Commons
Frédérique Chaucheyras‐Durand,

A. Sacy,

K. Karges

и другие.

Microorganisms, Год журнала: 2022, Номер 10(12), С. 2517 - 2517

Опубликована: Дек. 19, 2022

Horses are large non-ruminant herbivores and rely on microbial fermentation for energy, with more than half of their maintenance energy requirement coming from occurring in enlarged caecum colon. To achieve that, the gastro-intestinal tract (GIT) horses harbors a broad range various microorganisms, differing each GIT segment, which essential efficient utilization feed, especially to use nutrients that not or little degraded by endogenous enzymes. In addition, like other animal species, microbiota is permanent interplay host's cells involved lot functions among inflammation, immune homeostasis, metabolism. As animals humans, horse gut microbiome sensitive diet, consumption starch, fiber, fat. Age, breeds, stress during competitions, transportation, exercise may also impact microbiome. Because its size complexity, equine prone perturbations caused external internal stressors result digestive diseases gastric ulcer, diarrhea, colic, colitis, thought be linked systemic laminitis, metabolic syndrome obesity. Thus, this review we aim at understanding common core -in terms structure function- segment GIT, as well identifying potential biomarkers health disease crucial anticipate putative perturbations, optimize global practices develop adapted nutritional strategies personalized nutrition.

Язык: Английский

Процитировано

33

Human Norovirus Efficiently Replicates in Differentiated 3D-Human Intestinal Enteroids DOI
Carmen Mirabelli, Nânci Santos-Ferreira, Merritt Gillilland

и другие.

Journal of Virology, Год журнала: 2022, Номер 96(22)

Опубликована: Ноя. 7, 2022

Human norovirus (HNoV) accounts for one-fifth of all acute viral gastroenteritis worldwide and an economic burden ~$60 billion globally. The lack treatment options against HNoV is in part due to the cultivation systems. Recently, a model infection biopsy-derived human intestinal enteroids (HIE) has been described: 3D-HIE are first dispersed 2D-monolayers differentiated prior infection, resulting labor-intensive, time-consuming procedure. Here, we present alternative protocol 3D-HIE. We found that as efficiently 2D-monolayers. In addition, immunofluorescence-based quantification UEA-1, lectin stains villus brush border, revealed ~80% spontaneously undergo polarity inversion, allowing without need microinjection. Infection with GII.4-positive stool samples attained fold-increase over inoculum ~2 Log10 at 2 days postinfection or up 3.5 when ruxolitinib, JAK1/2-inhibitor, was added. Treatment GII.4-infected polymerase inhibitor 2'-C-Methylcytidine (2CMC) other antivirals showed reduction suggesting excellent platform test anti-infectives. transcriptional host response then investigated by RNA sequencing infected versus uninfected presence ruxolitinib focus on virus-associated signatures while limiting interferon-stimulated gene signatures. analysis upregulated hormone neurotransmitter signal transduction pathways downregulated glycolysis hypoxia-response upon infection. Overall, have proven be highly robust study screen antivirals, investigate IMPORTANCE clinical socio-economic impact calls immediate action development Physiologically relevant vitro models hence needed biology, tropism, mechanisms viral-associated disease, also identify antiviral agents. Biopsy-derived biomimetic epithelium were recently described supports However, established labor-intensive. Therefore, sought develop simplified 3D undergoes differentiation spontaneous inversion. Advantages this shorter experimental time, better yield, spatial integrity epithelium. This potentially suitable pathogens infect cells from apical surface but unraveling interactions between indigenous bacteria microbiome.

Язык: Английский

Процитировано

29

Co-exposure of polystyrene nanoplastics and copper induces development toxicity and intestinal mitochondrial dysfunction in vivo and in vitro DOI

Jinyu Rong,

Chenwei Yuan,

Yin Xiang

и другие.

The Science of The Total Environment, Год журнала: 2024, Номер 930, С. 172681 - 172681

Опубликована: Апрель 24, 2024

Язык: Английский

Процитировано

9

Gut–Brain Interactions and Their Impact on Astrocytes in the Context of Multiple Sclerosis and Beyond DOI Creative Commons

Julia Zißler,

Veit Rothhammer, Mathias Linnerbauer

и другие.

Cells, Год журнала: 2024, Номер 13(6), С. 497 - 497

Опубликована: Март 13, 2024

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) that leads to physical and cognitive impairment in young adults. The increasing prevalence MS underscores critical need for innovative therapeutic approaches. Recent advances neuroimmunology have highlighted significant role gut microbiome pathology, unveiling distinct alterations patients’ microbiota. Dysbiosis not only impacts gut-intrinsic processes but also influences production bacterial metabolites hormones, which can regulate remote tissues, such as CNS. Central this paradigm gut–brain axis, bidirectional communication network linking gastrointestinal tract brain spinal cord. Via specific routes, hormones influence CNS-resident cells both directly indirectly. Exploiting novel interventions, including pro- prebiotic treatments, emerged promising avenues with aim mitigating severity MS. This review delves into complex interplay between context MS, summarizing current knowledge on key signals cross-organ crosstalk, routes communication, potential relevance microbiome. Moreover, places particular emphasis elucidating these interactions astrocyte functions within CNS, offering insights their pathophysiology interventions.

Язык: Английский

Процитировано

8