Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Язык: Английский

---

The gut virome: A new microbiome component in health and disease

EBioMedicine, Год журнала: 2022, Номер 81, С. 104113 - 104113

Опубликована: Июнь 23, 2022

The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. virome is highly heterogeneous across populations and linked to geography, ethnicity, diet, lifestyle, urbanisation. currently function varies greatly populations, much remains unknown. We review current literature on virome, intricate trans-kingdom interplay among bacteria, mammalian host underlying health diseases. summarise evidence use diagnostic markers a therapeutic target. shed light novel avenues microbiome-inspired diagnosis therapies. also pre-clinical clinical studies virome-rectification-based therapies, including faecal microbiota transplantation, refined phage therapy. Our suggests that future research effort should focus unravelling mechanisms exerted by viruses/phages in pathophysiology, developing phage-prompted precision

Язык: Английский

---

Targeting the gut microbiota for cancer therapy

Nature reviews. Cancer, Год журнала: 2022, Номер 22(12), С. 703 - 722

Опубликована: Окт. 17, 2022

Язык: Английский

---

Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Advanced Science, Год журнала: 2023, Номер 10(23)

Опубликована: Июнь 1, 2023

Colorectal cancer (CRC) is the most common of digestive system with high mortality and morbidity rates. Gut microbiota found in intestines, especially colorectum, has structured crosstalk interactions host that affect several physiological processes. The gut include CRC-promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, CRC-protecting Clostridium butyricum, Streptococcus thermophilus, Lacticaseibacillus paracasei, which along other microorganisms, viruses fungi, play critical roles development CRC. Different features are identified patients early-onset CRC, combined different patterns between fecal intratumoral microbiota. may be beneficial diagnosis treatment CRC; some bacteria serve biomarkers while others regulators chemotherapy immunotherapy. Furthermore, metabolites produced by essential CRC cells. Harmful primary bile acids short-chain fatty acids, whereas others, including ursodeoxycholic acid butyrate, impede tumor progression. This review focuses on its metabolites, their potential development, diagnosis,

Язык: Английский

---

Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 1, 2023

Abstract Parabacteroides distasonis ( P. ) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that is decreased patients with hepatic fibrosis, administration of to male mice improves thioacetamide (TAA)- methionine choline-deficient (MCD) diet-induced fibrosis. Administration also leads increased bile salt hydrolase (BSH) activity, inhibition intestinal farnesoid X receptor (FXR) signaling taurochenodeoxycholic acid (TCDCA) levels liver. TCDCA produces toxicity mouse primary cells (HSCs) induces mitochondrial permeability transition (MPT) Caspase-11 pyroptosis mice. The decrease by activation HSCs through decreasing MPT-Caspase-11 hepatocytes. Celastrol, a compound reported increase abundance mice, promotes the growth concomitant enhancement excretion improvement fibrosis These data suggest supplementation may be promising means ameliorate

Язык: Английский

---

Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Язык: Английский

---

Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

Gut, Год журнала: 2022, Номер 71(12), С. 2574 - 2586

Опубликована: Сен. 16, 2022

The diet and gut microbiota have been extensively interrogated as a fuel for inflammation in inflammatory bowel diseases (IBDs) the last few years. Here, we review how specific nutrients, typically enriched Western diet, instigate or deteriorate experimental genetically susceptible host discuss microbiota-dependent independent mechanisms. We depict study landscape of nutritional trials paediatric adult IBD delineate common grounds dietary advice. Conclusively, reflects critical rheostat microbial dysbiosis IBD. Dietary restriction by exclusive enteral nutrition, with without exclusion is effectively treating Crohn’s disease, while are less conclusive. Insights into molecular mechanisms therapy will change perception allow us to enter era precision nutrition. To achieve this, need carefully designed scientific rigour comparable medical trials, which also requires action from stake holders. Establishing evidence-based does not only hold promise avoid long-term immunosuppression, but provide widely accessible at low cost. Identification culprits disturbing health bears potential prevent allows informed decision making food politics.

Язык: Английский

---

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

---

Chenodeoxycholic acid suppresses AML progression through promoting lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway and inhibiting M2 macrophage polarization

Redox Biology, Год журнала: 2022, Номер 56, С. 102452 - 102452

Опубликована: Авг. 30, 2022

Bile acids are steroid synthesized in liver, which essential for fat emulsification, cholesterol excretion and gut microbial homeostasis. However, the role of bile leukemia progression remains unclear. We aim at exploring effects mechanisms chenodeoxycholic acid (CDCA), a type acids, on acute myeloid (AML) progression. Here, we found that CDCA was decreased feces plasma AML patients, positively correlated with diversity microbiota, negatively associated prognosis. further demonstrated suppressed both vivo vitro. Mechanistically, bound to mitochondria cause mitochondrial morphology damage containing swelling reduction cristae, membrane potential elevated calcium level, resulted production excessive reactive oxygen species (ROS). Elevated ROS activated p38 MAPK signaling pathway, collaboratively promoted accumulation lipid droplets (LDs) through upregulating expression diacylglycerol O-acyltransferase 1 (DGAT1). As consequence abundance LDs, peroxidation enhanced cells. Moreover, uncovered inhibited M2 macrophage polarization proliferation-promoting macrophages cells co-cultured experiments. Our findings demonstrate suppresses synergistically promoting LDs via ROS/p38 MAPK/DGAT1 pathway caused by dysfunction inhibiting polarization.

Язык: Английский

---

Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation

Journal of Autoimmunity, Год журнала: 2023, Номер 141, С. 103062 - 103062

Опубликована: Май 27, 2023

Язык: Английский

---