Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Май 9, 2023

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM increasing globally, growing body evidence suggests that gut microbiota dysbiosis may contribute to the development this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan indole derivatives, short-chain fatty have been shown be involved in pathogenesis T2DM, playing key role host-microbe crosstalk. This review aims summarize molecular links between metabolites T2DM. Additionally, we potential therapy treatments for using probiotics, prebiotics, fecal transplantation other methods modulate its metabolites. Clinical trials investigating critically discussed. highlights targeting could therapeutic strategy prevention treatment

Язык: Английский

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Multifaceted bioactivity of thiosemicarbazide derivatives: Synthesis, characterization, and DFT investigations on inhibition of α-amylase, hydroxyl radical scavenging, and iron chelating activities with molecular docking insights

Journal of Molecular Structure, Год журнала: 2024, Номер 1304, С. 137669 - 137669

Опубликована: Янв. 29, 2024

Язык: Английский

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The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 27, 2024

Obesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts immune signaling leading endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the barrier but also exert immunomodulatory effects via G protein-coupled receptor binding epigenetic regulation. are emerging as potential agents counteract dysbiosis-induced changes, specifically targeting genes through DNA methylation, histone acetylation, microRNAs (miRNAs), long non-coding RNAs (lncRNAs). To assess whether can effectively interrupt detrimental cascade obesity this review aims provide a comprehensive overview current evidence for their clinical application. The emphasizes factors influencing SCFA production, intricate connections between metabolism, system, microbiome, mechanisms regulated by that impact metabolism system.

Язык: Английский

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When short-chain fatty acids meet type 2 diabetes mellitus: Revealing mechanisms, envisioning therapies

Biochemical Pharmacology, Год журнала: 2025, Номер 233, С. 116791 - 116791

Опубликована: Фев. 1, 2025

Язык: Английский

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Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach

Gut Microbes, Год журнала: 2023, Номер 15(1)

Опубликована: Июнь 14, 2023

Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be in the state of NAFLD. Using a fecal transplantation (FMT) intervention, we aimed to investigate whether change composition relates assessed plasma metabolite profiles by FMT relate changes methylation. Twenty-one individuals NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous 11) FMTs. We obtained from paired biopsies study participants before and after applied multi-omics machine learning approach identify microbiome, peripheral blood metabolome methylome, analyzed cross-omics correlations. Vegan compared induced distinct differential I) profiles, including increased abundance Eubacterium siraeum potential probiotic Blautia wexlerae; II) metabolites, levels phenylacetylcarnitine (PAC) phenylacetylglutamine (PAG) both gut-derived phenylacetic acid, several choline-derived long-chain acylcholines; III) most importantly Threonyl-TRNA Synthetase 1 (TARS) Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis Firmicutes bacterium_CAG_170 positively correlated PAC PAG. E negatively cg16885113 ZFP57. Alterations caused widespread metabolites (e.g. PAC, PAG, metabolites) These results indicate FMTs might induce metaorganismal pathway changes, bacteria liver.

Язык: Английский

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Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity

The American Journal of Chinese Medicine, Год журнала: 2023, Номер 51(03), С. 677 - 699

Опубликована: Янв. 1, 2023

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights necessity urgency to explore novel therapies. Sijunzi Decoction (SJZD), classical Chinese herbal formula, been comprehensively applied clinically proven in treating UC; however, pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis intestinal barrier integrity DSS-induced colitis. significantly alleviated colonic tissue damage improved goblet cell count, MUC2 secretion, tight junction protein expressions, which indicated enhanced integrity. remarkedly suppressed abundance phylum Proteobacteria genus Escherichia-Shigella, are typical features microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight colon length, positively disease activity index IL-1[Formula: see text]. Furthermore, through gut depletion, confirmed exerted anti-inflammatory activities microbiota-dependent manner, fecal transplantation (FMT) validated mediating role treatment UC. Through microbiota, modulates biosynthesis bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), identified as signature BA during treatment. Cumulatively, our findings disclose attenuates UC via orchestrating modulation integrity, thus offering promising alternative approach clinical management

Язык: Английский

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Novel hydrazone schiff’s base derivatives of polyhydroquinoline: synthesis, in vitro prolyl oligopeptidase inhibitory activity and their Molecular docking study

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 15

Опубликована: Фев. 22, 2024

This research work reports the synthesis of new derivatives hydrazone Schiff bases (1–17) based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS,1H- and 13C-NMR spectroscopy were used to structurally infer all synthesized compounds lastly evaluated for prolyl oligopeptidase inhibitory activity. All prepared products displayed good excellent activity when compared with standard z-prolyl-prolinal. Three 3, 15 14 showed inhibition IC50 values 3.21 ± 0.15 5.67 0.18 µM, while remaining 12 significant Docking studies indicated a correlation biochemical potency estimated in in-vitro test 14. The MD simulation results confirmed stability most potent inhibitors at 250 ns using parameters RMSD, RMSF, Rg number hydrogen bonds. RMSD indicate protein backbone complex over time. RMSF binding site residues that contributed stabilizing these regions protein, formed stable interactions protein. Rg. analysis assesses overall size compactness complexes. maintenance bonds suggests existence favorable interactions. SASA they maintained conformations without large-scale exposure solvent. These ligand–protein are could be exploited design drugs disease treatment.

Язык: Английский

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Secretory molecules from secretion systems fine-tune the host-beneficial bacteria (PGPRs) interaction

Frontiers in Microbiology, Год журнала: 2024, Номер 15

Опубликована: Фев. 26, 2024

Numerous bacterial species associate with plants through commensal, mutualistic, or parasitic association, affecting host physiology and health. The mechanism for such association is intricate involves the secretion of multiple biochemical substances dedicated protein systems called SS. Eleven SS pathways deliver factors enzymes in their immediate environment cells, as well competing microbial cells a contact-dependent independent fashion. These are instrumental competition, initiation infection, colonization, establishment (positive negative) organisms. role infection pathogenesis has been demonstrated several phytopathogens, including Agrobacterium, Xanthomonas, Ralstonia, Pseudomonas . Since there overlap mechanisms establishing plants, studies have investigated SSs interaction plant beneficial bacteria, symbiotic rhizobia growth bacteria (PGPB). Therefore, present review updates different required colonization rhizobia, Burkholderia, Pseudomonas, Herbaspirillum , etc., on inside which can lead to long-term association. Most like T3SS, T4SS, T5SS, T6SS antagonistic activity needed prevent microbes, ameliorate biotic stress produce successful colonization. Others chemotaxis, adherence, niche formation, suppression immune response establish mutualistic plants.

Язык: Английский

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Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations

Journal of Molecular Structure, Год журнала: 2024, Номер 1311, С. 138459 - 138459

Опубликована: Апрель 28, 2024

Язык: Английский

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Investigation the biological activities and the metabolite profiles of endophytic fungi isolated from Gundelia tournefortii L.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Март 25, 2024

Abstract Endophytic fungi are microorganisms that considered as a potential source of natural compounds, and can be applied in various industries. The aims this research were molecular identification endophytic isolated from the Gundelia tournefortii stems, investigation their biological activities well phenolic fatty acid profile. Surface sterilized stems G. placed on potato dextrose agar (PDA) to isolate fungal endophytes. Genomic DNA was extracted by CTAB method, PCR amplification performed ITS 1 4 primers. enzyme production determined based formation clear zone appeared around colonies fungus. anti-oxidant activity evaluated measuring amount free radicals DPPH. Also, total phenol flavonoid contents measured obtained Folin-Ciocalteu aluminum chloride colorimetric methods, respectively. Moreover, separation acids done HPLC GC, Phylogenetic analysis Internal Transcribed Spacer (ITS) region, five isolates identified following: Aspergillus niger , Penicillium glabrum Alternaria alternata A. tenuissima Mucor circinelloides . Evaluation enzymatic properties showed P. gabrum (31 ± 1.9 mm), (23 1.7) had more ability for producing pectinase cellulase. extract (IC 50 = 471 29 µg/mL) highest properties, followed 512 19 µg/mL). greatest phenols flavonoids (8.2 0.4 mg GAL/g 2.3 0.3 QE/g, respectively). quantification rosmarinic acid, para-coumaric meta-coumaric (42.02 1.31, 7.53 0.19, 5.41 0.21 mg/g, respectively) main studied fungi. confirmed that, all fungi, stearic (27.9–35.2%), oleic (11.3–17.3%), palmitic (16.9–23.2%), linoleic (5.8–11.6%), caprylic (6.3–10.9%). Our finding bioactive which could used This is first report associated with provides knowledge future use biotechnological processes.

Язык: Английский

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