Imbalance of Bile Acids Metabolism Mediated by Gut Microbiota Contributed to Metabolic Disorders in Diabetic Model Mice DOI Creative Commons

Haiping Dong,

Xinguo Liu, Ge Song

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(3), P. 291 - 291

Published: March 13, 2025

Type 2 diabetes (T2D) is a chronic disease prevalent in the world, accompanied by variety of diseases, endangering human health and safety. Bile acids (BAs) play an important role regulation host glucose lipid metabolism homeostasis, are strictly regulated gut microbiota. However, relationship between key BAs, BAs transporters signaling, as well microbiota, T2D remains elusive. In this study, 9-week-old db/db mice were used model (db/db group, n = 10), their wild-type (wt) littermates same age healthy control (CON 10). After 8 weeks feeding, BA profiles microbial composition colon, gene expression level regulatory factors analyzed CON groups to explore underlying mechanisms T2D. Compared with mice, body weight, blood levels significantly increased. The concentrations total primary conjugated non-12α–hydroxylated (non-12–OH BAs) decreased, while Deoxycholic acid (DCA) secondary was increased group. wt synthesis liver transformed from alternative pathway classical pathway, hepatic (NTCP, BSEP, MRP2, OATP–1 OSTβ) receptors (FXR TGR5) down-regulated mice. mRNA FXR up-regulated, TGR5 down-regulated. diabetic (db/db) presented changed microbiota composition, including abundance BAs-producing bacteria, Escherichia–Shigella, decreased Akkermansia, which involved non-12–OH BAs. We further found that reduced types negatively correlated metabolic-disorder-related indicators, DCA had opposite correlation. Our results shed light into how imbalance BAs’ mediated intestinal flora may be potential

Language: Английский

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases DOI Creative Commons
Linsen Shi, Lihua Jin, Wendong Huang

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(14), P. 1888 - 1888

Published: July 19, 2023

The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of pathological molecules microorganisms. Bile acids are small synthesized cholesterol in liver, secreted into duodenum, transformed to secondary or tertiary bile by gut microbiota. interact with acid receptors (BARs) microbiota, which plays key role maintaining homeostasis barrier. In this review, we summarize discuss recent studies on disorder associated dysfunction related diseases. We focus roles acids, BARs, microbiota triggering dysfunction. Insights for future prevention treatment diseases provided.

Language: Английский

Citations

43

Novel mechanism by which extracellular vesicles derived from Lactobacillus murinus alleviates deoxynivalenol-induced intestinal barrier disruption DOI Creative Commons
Jinping Fan, Yuhan Zhang,

Mong-Yee Zuo

et al.

Environment International, Journal Year: 2024, Volume and Issue: 185, P. 108525 - 108525

Published: Feb. 22, 2024

Deoxynivalenol (DON) is a common environmental pollutant that poses serious health risk to humans worldwide. This study was aim explore whether gut microbiota involved in DON-induced intestinal toxicity as well reveal effect of probiotics derived from protecting barrier and elucidate mechanism. We found DON caused disturbed microbiota, particularly Lactobacillus murinus (L. murinus) deficiency. enhanced M1 macrophage polarization decreased tight junction protein expression. Microbiota transplantation experiments showed transfer DON-disrupted healthy mice resulted delivery toxicity. Besides, lost its damaging on antibiotic-treated mice. Further intervention revealed L. induce conversion M2 phenotype through secreted extracellular vesicles (EVs) alleviate disruption. Mechanistically, EVs activate TLR2 promote release IL-10, which turn enhances function. Upon successful translation efficacy into clinical practice, created could be novel possible treatment strategy for disease.

Language: Английский

Citations

27

Gut microbiota as a key regulator of intestinal mucosal immunity DOI
Jing Wang, Mei He, Ming Yang

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 345, P. 122612 - 122612

Published: April 6, 2024

Language: Английский

Citations

17

Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation DOI Creative Commons
Dandan Han, Yujun Wu,

Dongdong Lu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(10)

Published: Oct. 9, 2023

Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual affect the interactions between macrophages in context of inflammatory bowel disease (IBD). Here, we aim to elucidate mechanism by which inflammation. Mice with or without depletion were administered four including chlorogenic, ferulic, caffeic, ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut fecal transplantation further performed mice investigate role acid-mediated protective effect. Colitis severity was evaluated using histological, serological, immunological measurements. Absence deteriorate epithelial injury DSS colitis. Chlorogenic acid mitigated colitis reducing M1 polarization suppression pyruvate kinase M 2 (Pkm2)-dependent glycolysis inhibition NOD-like receptor protein 3 (Nlrp3) ferulic reduction neutrophil-dependent diminishing formation neutrophil extracellular traps. On other hand, beneficial effects caffeic dependent upon microbiota. In fact, urolithin A (UroA), a metabolite transformed from microbiota, found enhance barrier function an IL22-dependent manner. Overall, our findings demonstrated that mechanisms protected against resulted interaction macrophage-neutrophil.

Language: Английский

Citations

33

Lactobacillus brevis alleviates the progress of hepatocellular carcinoma and type 2 diabetes in mice model via interplay of gut microflora, bile acid and NOTCH 1 signaling DOI Creative Commons
Shujia Chen, Ping Han, Qian Zhang

et al.

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

Published: May 10, 2023

Type 2 diabetes (T2DM) clinically exhibits a higher incidence of hepatocellular carcinoma (HCC), contributing to lousy prognosis in patients harboring both diseases. Microflora-based therapy draws attention with low side effects. Accumulating evidence shows that Lactobacillus brevis can improve blood glucose and body weight the T2DM mice model reduce several cancer incidences. However, therapeutic effect affecting T2DM+HCC remains unknown. In this study, we aim explore question via an established model. We observed significant alleviation after probiotic intervention. improves insulin resistance ameliorates Mechanically. Combined multi-omics approach including 16SrDNA, GC-MS, RNA-seq, identified distinct intestinal microflora composition metabolites Furthermore, found delayed disease progression by regulating MMP9 NOTCH 1 signaling pathways, potentially through gut BA interaction. This study indicates may + HCC, providing novel opportunities targeting flora for T2DM+HCC.

Language: Английский

Citations

25

Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis DOI Creative Commons
Hao Zhang,

Xia Zha,

Bei Zhang

et al.

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 17, 2024

Abstract Background Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed BPA exposure causes placental apoptosis and oxidative stress (OS) decreases efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum (ERS), OS maternal placenta intestine are unclear ovine model gestation. Results Two ewe groups ( n = 8/group) were given either a subcutaneous (sc) injection corn oil (CON group) or (5 mg/kg/day) dissolved (BPA once daily, from day 40 110 The colonic digesta ileum tissue samples collected measure biomarkers ERS, OS. To investigate link between BPA-induced FGR ewes, transplantation (GMT) was conducted two mice 10/group) 0 18 gestation after removing their intestinal by antibiotics. results indicated aggravates ERS function injury ileum, dysbiosis ewes. GMT attributed resulting exposure. Conclusions Our findings indicate underlying gut-placental axis behind OS, further provide novel insights into modulating balance through medication probiotics, functioning via axis, alleviate gut-derived impairment

Language: Английский

Citations

14

Characterizing core microbiota and regulatory functions of the pig gut microbiome DOI Creative Commons
Jun Hu, Jianwei Chen,

Libao Ma

et al.

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

Abstract Domestic pigs (Sus scrofa) are the leading terrestrial animals used for meat production. The gut microbiota significantly affect host nutrition, metabolism, and immunity. Hence, characterization of microbial structure function will improve our understanding resources mechanisms underlying host–microbe interactions. Here, we investigated microbiomes seven pig breeds using metagenomics 16S rRNA gene amplicon sequencing. We established an expanded reference catalog comprising 17 020 160 genes identified 4910 metagenome-assembled genomes. also analyzed resistome to provide overview profiles antimicrobial resistance in pigs. By analyzing relative abundances microbes, three core-predominant microbes (Phascolarctobacterium succinatutens, Prevotella copri, Oscillibacter valericigenes) this study. Oral administration increased organ indexes (including heart, spleen, thymus), but decreased gastrointestinal lengths germ-free mice. core enhanced intestinal epithelial barrier altered mucosal morphology, as was evident from increase crypt depths duodenum ileum. Furthermore, affected several metabolic pathways (such “steroid hormone biosynthesis,” “primary bile acid “phenylalanine, tyrosine tryptophan “phenylalanine metabolism”) These findings a panoramic view microbiome insights into functional contributions host.

Language: Английский

Citations

10

Interactions between Gut Microbiota and Natural Bioactive Polysaccharides in Metabolic Diseases: Review DOI Open Access
Yu Pi,

Miaoyu Fang,

Yanpin Li

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(17), P. 2838 - 2838

Published: Aug. 24, 2024

The gut microbiota constitutes a complex ecosystem, comprising trillions of microbes that have co-evolved with their host over hundreds millions years. Over the past decade, growing body knowledge has underscored intricate connections among diet, microbiota, and human health. Bioactive polysaccharides (BPs) from natural sources like medicinal plants, seaweeds, fungi diverse biological functions including antioxidant, immunoregulatory, metabolic activities. Their effects are closely tied to which metabolizes BPs into health-influencing compounds. Understanding how interact is critical for harnessing potential health benefits. This review provides an overview focusing on its role in diseases obesity, type II diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular diseases. It explores basic characteristics several impact microbiota. Given significance health, we summarize these BPs, particularly terms immunoregulatory activities, blood sugar, hypolipidemic effect, thus providing valuable reference understanding benefits treating These properties make promising agents preventing comprehensive mechanisms by exert through opens new avenues developing targeted therapies improve

Language: Английский

Citations

9

Microbial sensing in the intestine DOI Creative Commons
Tingting Wan, Yalong Wang, Kaixin He

et al.

Protein & Cell, Journal Year: 2023, Volume and Issue: 14(11), P. 824 - 860

Published: May 16, 2023

The gut microbiota plays a key role in host health and disease, particularly through their interactions with the immune system. Intestinal homeostasis is dependent on symbiotic relationships between diverse microbiota, which influenced by highly co-evolved immune-microbiota interactions. first step of interaction sensing microbes In this review, we describe cells system proteins that sense components metabolites microbes. We further highlight essential roles pattern recognition receptors (PRRs), G protein-coupled (GPCRs), aryl hydrocarbon receptor (AHR) nuclear expressed intestinal epithelial (IECs) intestine-resident cells. also discuss mechanisms disruption microbial because genetic or environmental factors causes human diseases such as inflammatory bowel disease (IBD).

Language: Английский

Citations

20

Gut microbiota-derived 12-ketolithocholic acid suppresses the IL-17A secretion from colonic group 3 innate lymphoid cells to prevent the acute exacerbation of ulcerative colitis DOI Creative Commons
Na Li,

Pei-guang Ma,

Yalan Li

et al.

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Dec. 8, 2023

Intestinal microbiota dysbiosis and metabolic disruption are well-known as the primary triggers of ulcerative colitis (UC). However, their role in regulating group 3 innate lymphoid cells (ILC3s), which essential for intestinal health, remains unexplored during development disease severity. Here, our results showed that structure patients with severe UC (SUCs) differed from those mild (MiUCs), moderate (MoUCs), healthy controls (HCs). Microbes producing secondary bile acids (SBAs) SBAs decreased aggravation UC, a strong positive correlation existed between them. Next, fecal transfer was used to reproduce human-derived mice decipher microbiota-mediated inflammatory modulation an increase Mice receiving SUC-derived exhibited enhancive inflammation, lowered percentage ILC3s, down-regulated expressions acid receptors, including vitamin D receptor (VDR) pregnane X (PXR), colon. Similar clinical results, SBA-producing microbes, deoxycholic (DCA), 12-ketolithocholic (12-KLCA) were diminished intestine these recipients. Finally, we compared therapeutic potential DCA 12-KLCA preventing regulatory mechanisms mediated by ILC3s. but not represented anti-inflammatory effect associated higher expression VDR lower secretion IL-17A colonic Collectively, findings provide new signatures monitoring acute deterioration targeting gut metabolism demonstrate preventive novel microbiota-derived metabolite, 12-KLCA.

Language: Английский

Citations

20