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1.
J Int Med Res ; 52(5): 3000605241241000, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38749910

RESUMO

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.


Assuntos
Colite , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Ileostomia , Humanos , Masculino , Idoso , Transplante de Microbiota Fecal/métodos , Colite/microbiologia , Colite/terapia , Transplante Homólogo/métodos , Resultado do Tratamento , Colonoscopia
2.
J Hepatol ; 73(2): 383-393, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32147363

RESUMO

BACKGROUND & AIMS: Circulating peptides and G protein-coupled receptors (GPCRs) have gained much attention because of their biofunctions in metabolic disorders including obesity and non-alcoholic fatty liver disease (NAFLD). Herein, we aimed to characterize the role and therapeutic potential of a newly identified peptide hormone in NAFLD. METHODS: Using bioinformatics, we identified a murine circulating pentadecapeptide flanked by potential convertase cleavage sites of osteocalcin (OCN), which we named 'metabolitin (MTL)'. We used ligand-receptor binding, receptor internalization, bioluminescence resonance energy transfer and Nano isothermal titration calorimetry assays to study the binding relationship between MTL and GPRC6A. For in vivo biological studies, wild-type mice kept on a high-fat diet (HFD) were injected or gavaged with MTL to study its function in NAFLD. RESULTS: We confirmed that MTL binds to GPRC6A and OCN interacts with GPRC6A using in vitro biological studies. Both intraperitoneal and oral administration of MTL greatly improved NAFLD and insulin resistance in a mouse model. Interacting with GPRC6A expressed in intestines, MTL can significantly inhibit intestinal neurotensin secretion, which in turn inhibits triglyceride but not cholesterol gut absorption, mediated by the 5'AMP-activated protein kinase pathway. In addition, glucagon like peptide-1 secretion was induced by MTL treatment. CONCLUSIONS: Oral or intraperitoneal MTL significantly improves the symptoms of NAFLD by inhibiting lipid absorption and insulin resistance. MTL could be a potential therapeutic candidate for the treatment of NAFLD. LAY SUMMARY: A novel murine peptide hormone, herein named 'metabolitin', inhibits fatty acid absorption and improves systemic insulin resistance in a murine model of obesity and non-alcoholic fatty liver disease. Thus, metabolitin has therapeutic potential for the treatment of patients with non-alcoholic fatty liver disease.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/metabolismo , Absorção Intestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica , Hormônios Peptídicos , Receptores Acoplados a Proteínas G/metabolismo , Triglicerídeos/metabolismo , Animais , Gorduras na Dieta/metabolismo , Modelos Animais de Doenças , Hipolipemiantes/metabolismo , Hipolipemiantes/farmacologia , Resistência à Insulina , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Osteocalcina/metabolismo , Hormônios Peptídicos/metabolismo , Hormônios Peptídicos/farmacologia , Transdução de Sinais , Resultado do Tratamento
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