Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway

Cell, Год журнала: 2024, Номер 187(11), С. 2717 - 2734.e33

Опубликована: Апрель 22, 2024

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but mechanisms have not established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage patients liver-tissue-biopsy-proven fatty disease (MAFLD). By screening human bacterial isolates, Bacteroides uniformis strains as effective producers 3-sucCA both vitro and vivo. activity-based protein purification identification, enzyme annotated β-lactamase B. responsible for biosynthesis. Furthermore, that lumen-restricted metabolite alleviates MASH promoting growth Akkermansia muciniphila. Together, our data offer new insights into microbiota-liver axis may be leveraged augment management MASH.

Язык: Английский

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Glycine homeostasis requires reverse SHMT flux

Cell Metabolism, Год журнала: 2024, Номер 36(1), С. 103 - 115.e4

Опубликована: Янв. 1, 2024

Язык: Английский

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Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD

Cell Metabolism, Год журнала: 2024, Номер 36(1), С. 116 - 129.e7

Опубликована: Янв. 1, 2024

Язык: Английский

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Gouqi-derived nanovesicles (GqDNVs) inhibited dexamethasone-induced muscle atrophy associating with AMPK/SIRT1/PGC1α signaling pathway

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 22, 2024

Abstract With the increasing trend of global aging, sarcopenia has become a significant public health issue. Goji berry, also known as “Gou qi zi” in China, is traditional Chinese herb that can enhance structure and function muscles bones. Otherwise, previous excellent publications illustrated plant-derived exosome-like nanoparticles exert good bioactive functions different aging or disease models. Thus, we issued hypothesis Gouqi-derived nanovesicles (GqDNVs) may have ability to improve skeletal muscle health, though effect its mechanism need be explored. Hence, extracted GqDNVs from fresh berries Lycium barbarum L. (goji) found contents are rich saccharides lipids. Based on pathway annotations predictions non-targeted metabolome analysis, tightly associated with pathways metabolism. In atrophy model mice, intramuscular injection improves cross-sectional area quadriceps muscle, grip strength AMPK/SIRT1/PGC1α expression. After separately inhibiting AMPK PGC1α C2C12 cells dexamethasone administration, activated plays chief role improving cell proliferation induced by GqDNVs. Furthermore, energy-targeted analysis demonstrates up-regulate metabolism amino sugar nucleotide sugar, autophagy oxidative phosphorylation process, which indicates activation regeneration. Besides, Spearman rank shows close associations between quality metabolites expression levels SIRT1. this study, provide new founding accompanying signaling pathway. Therefore, anti-aging potential adjuvant complementary method idea future therapy research. Graphical

Язык: Английский

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Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease

American Journal Of Pathology, Год журнала: 2024, Номер 194(4), С. 510 - 524

Опубликована: Янв. 1, 2024

Язык: Английский

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Global research trends on gut microbiota and metabolic dysfunction-associated steatohepatitis: Insights from bibliometric and scientometric analysis

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 11, 2024

Background Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of metabolic steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD, common, multifactorial and poorly understood whose incidence increasing worldwide. In recent years, there scientific interest in exploring the relationship between gut microbiota MASH. To learn more about MASH, this study aims to provide comprehensive analysis knowledge structure research hotspots from bibliometric perspective. Methods We searched Web Science Core Collection articles reviews that covered connections MASH over last decade. The Online Analysis Platforms, VOSviewer, CiteSpace, R tool “bibliometrix” were used analyzed existing publications trends hotspots. Results A total 4,069 documents related interaction retrieved 2014 2023. number annual increased significantly decade, particularly United States China. University California-San Diego was most productive institution, while researcher Rohit Loomba published papers field. Younossi ZM ranked first co-cited author largest contributor highly cited Gastroenterology hepatology common specialty category. journal decade Hepatology. Keyword Bursts highlighted importance studying association well factors such syndrome, insulin resistance, endotoxemia overgrowth bacteria. clusters with co-citation illustrate important topics including intestinal permeability, sensitivity immunology. keywords include obesity, dysbiosis, inflammation oxidative stress, which are current Conclusion Our highlights key aspects field emphasizes multiorgan crosstalk MASLD/MASH pathogenesis. particular, central role gut-liver axis significant influence dysbiosis on progression highlighted. Furthermore, our results highlight transformative potential microbiota-specific therapies cover way innovative healthcare pharmaceutical strategies.

Язык: Английский

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Effects of sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute on Metabolic Regulation in Sprague-Dawley Rats

Nutrients, Год журнала: 2024, Номер 16(9), С. 1299 - 1299

Опубликована: Апрель 26, 2024

In this study, the influence of total sn-2 palmitic triacylglycerols (TAGs) and ratio 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on metabolic changes were investigated Sprague–Dawley rats. Metabolomics lipidomics profiling analysis indicated that increasing TAGs OPL OPO HMFS could significantly glycine, serine threonine metabolism, glycerophospholipid glycerolipid sphingolipid bile acid biosynthesis, taurine hypotaurine metabolism pathways rats after 4 weeks feeding, which mainly related lipid, energy metabolism. Meanwhile, up-regulation taurine, L-tryptophan, L-cysteine, down-regulations lysoPC (18:0) hypoxanthine would contribute reduction inflammatory response oxidative stress, improvement immunity function addition, targeted biochemical factors also revealed HMFS-fed had increased levels anti-inflammatory factor (IL-4), immunoglobulin A (IgA), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), decreased pro-inflammatory (IL-6 TNF-α) malondialdehyde (MDA), compared with those control fat-fed Collectively, these observations present new vivo nutritional evidence for regulatory effects TAG structure composition substitutes host.

Язык: Английский

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The rheumatoid arthritis gut microbial biobank reveals core microbial species that associate and effect on host inflammation and autoimmune responses

iMeta, Год журнала: 2024, Номер 3(5)

Опубликована: Окт. 1, 2024

Abstract Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular culture‐independent studies revealed RA patients harbored a core microbiome had characteristic bacterial species, the lack of cultured strains limited investigations on their functions. This study aimed to establish an RA‐originated gut microbial biobank (RAGMB) that covers further correlates validates species clinically used diagnostic inflammation immune indices. We obtained 3200 isolates from fecal samples 20 with seven improved 11 traditional cultivation methods. These were phylogenetically identified selected for RAGMB. The RAGMB 601 represented 280 (including 43 novel species) phyla. covered 93.2% at level medium‐ high‐abundant (relative abundances ≥0.2%) microbes, included four rare phylum Synergistota . was defined composed species. Among these, Mediterraneibacter tenuis Eubacterium rectale two statistically significantly correlated indices such as erythrocyte sedimentation rate (ESR) IL‐10. Thus, M. E. experimental validation using DSS‐treated not mice model. Results demonstrated both exacerbated host inflammatory responses, including shortened colon length increased spleen weight, decreased IL‐10 IL‐17A levels plasma. Overall, we established RAGMB, microbiome, effected responses. work provides diverse resources future etiology potential new targets biomedical practices.

Язык: Английский

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Disentangling the molecular mystery of tumour–microbiota interactions: Microbial metabolites

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(11)

Опубликована: Ноя. 1, 2024

Abstract The profound impact of the microbiota on initiation and progression cancer has been a focus attention. In recent years, many studies have shown that microbial metabolites serve as key hubs connect microbiome progression, but underlying molecular mechanisms not fully elucidated. Multiple influence tumour development therapy resistance, including disrupting cellular signalling pathways, triggering oxidative stress, inducing metabolic reprogramming reshaping immune microenvironment, are reviewed. Focusing advancements in this field, review also summarises methodological framework regarding metabolites. review, we outline current state research tumour‐associated describe challenges future scientific clinical applications. Key points Metabolites derived from both gut intratumoural play important roles progression. dual pose an obstacle for translations. Absolute quantification tracing techniques essential addressing gaps Integrating metabolomics with multi‐omics transcends paradigms.

Язык: Английский

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Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR ^-/- Hamsters

Research, Год журнала: 2024, Номер 7

Опубликована: Янв. 1, 2024

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver cardiovascular diseases. Emerging evidence underscores the crucial role of intestinal microbiota in metabolic disorders. However, potential therapeutic viability remodeling CHL remains uncertain. In this study, was induced low-density lipoprotein receptor-deficient (LDLR -/- ) hamsters through an 8-week high-fat high-cholesterol (HFHC) diet or a 4-month (HC) diet. Placebo antibiotics were administered separate cohousing approaches. Analysis 16S rDNA sequencing revealed that intermittent antibiotic treatment approach effectively modulated gut community without impacting its overall abundance LDLR exhibiting severe CHL. Antibiotic mitigated HFHC diet-induced obesity, hyperglycemia, hyperlipidemia, enhancing thermogenesis alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions hamsters. Metabolomic analysis favorable lipid metabolism profile. Increased levels microbiota-derived metabolites, notably butyrate glycylglycine, also ameliorated NASH atherosclerosis diet-fed Notably, antibiotics, butyrate, glycylglycine exhibited protective effects on HC diet, aligning outcomes observed scenario. Our findings highlight efficacy improving NASH, refractory beneficial metabolites suggest avenue for microbiome-mediated therapies addressing CHL-associated

Язык: Английский

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