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Crosstalk between gut microbiota and antidiabetic drug action

World Journal of Diabetes 2019年第3期10卷 154-168页

作者： Yevheniia Kyriachenko tetyana falalyeyeva Oleksandr Korotkyi Nataliia Molochek Nazarii Kobyliak Educational and Scientific Centre “Institute of Biology and Medicine” Taras Shevchenko National University of Kyiv Kyiv 01601 Ukraine Endocrinology Department Bogomolets National Medical University Kyiv 01601 Ukraine

Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin,α-glucosidase inhibitors, glucagon-like peptide-1 agonists, peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2D, and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria, responsible for losing weight and suppressing inflammation.

关键词： Type 2 diabetes Gut microbiota Metformin α-glucosidase inhibitors Glucagon-like peptide-1 agonists Peroxisome proliferator-activated receptors γ agonists Dipeptidyl peptidase-4 inhibitors Sodium/glucose cotransporter inhibitors

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Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma:Relation to the immune cycle

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World Journal of Gastroenterology 2021年第31期27卷 5259-5271页

作者： Artem Mashukov Dmytro Shapochka Oleksii Seleznov Nazarii Kobyliak tetyana falalyeyeva Stanislav Kirkilevsky Roman Yarema Oksana Sulaieva Department of Oncology Odessa National Medical UniversityOdessa 65082Ukraine Department of Molecular Pathology and Genetics Medical Laboratory CSDKyiv 03022Ukraine Department of Pathology Medical Laboratory CSDKyiv 03022Ukraine Department of Endocrinology Bogomolets National Medical UniversityKyiv 01601Ukraine Biomedicine Educational-Scientific Center"Institute of Biology and Medicine"Taras Shevchenko National University of KyivKyiv 01601Ukraine Department of Thoracic Tumors National Cancer InstituteKyiv 03022Ukraine Department of Oncology and Medical Radiology Danylo Halytsky Lviv National Medical UniversityLviv 79010Ukraine

BACKGROUND Various histological types of gastric carcinomas(GCs)differ in terms of their pathogenesis and their preexisting background,both of which could impact the tumor immune microenvironment(TIME).However,the current understanding of the immune contexture of GC is far from *** To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle *** In total,50 GC cases were examined(15 cases of diffuse GC,31 patients with intestinal-type GC and 4 cases of mucinous GC).The immunophenotype of GC was assessed and classified as immune desert(ID),immune excluded(IE)or inflamed(Inf)according to CD8+cell count and spatial *** addition,CD68+and CD163+macrophages and programmed death-ligand 1(PD-L1)expression were *** We found that GCs with different histological differentiation demonstrated distinct immune *** intestinal-type GCs had inflamed TIMEs rich in both CD8+cells and *** contrast,more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+lymphocytes but abundant CD68+macrophages,while mucinous GC had an IE-TIME with a prevalence of CD68+macrophages and CD8+lymphocytes in the peritumor ***-L1 expression prevailed mostly in intestinal-type Inf-GC,with numerous CD163+cells ***,GCs of different histological patterns have specific mechanisms of immune *** intestinal-type GC was more often related to PD-L1 expression,diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor *** These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

关键词： Gastric carcinoma Tumor immune microenvironment Tumor infiltrating lymphocytes Tumor associated macrophages

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Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment

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World Journal of Hepatology 2022年第3期14卷 634-646页

作者： Elina Manzhalii Valentyna Moyseyenko Vitalii Kondratiuk Nataliia Molochek tetyana falalyeyeva Nazarii Kobyliak Department of Propedeutics of Internal Medicine Bogomolets National Medical UniversityKyiv 01601Ukraine Educational and Scientific Centre“Institute of Biology and Medicine” Taras Shevchenko National University of KyivKyiv 01601Ukraine Department of Pediatrics Bogomolets National Medical UniversityKyiv 01601Ukraine Department of Scientific Medical Laboratory CSDKyiv 01004Ukraine Department of Endocrinology Bogomolets National Medical UniversityKyiv 01601Ukraine

BACKGROUND Hepatic encephalopathy(HE)can be considered a result of dysregulated gutliver-brain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by"gut-centric"therapies,such as the administration of nonabsorbable disaccharides,nonabsorbable antibiotics,probiotics and *** To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle(EcN)1917 strain compared to lactulose and rifaximin in patients with minimal/mild *** From January 2017 to March 2020,a total of 45 patients with HE were enrolled in this prospective,single-centre,open-label,randomized *** were randomly assigned at a ratio of 1:1:1 to one of the treatment groups:The EcN group(n=15),lactulose group(n=15)or rifaximin group(n=15)for a 1 mo intervention *** main primary outcomes of the study were changes in serum ammonia and Stroop test *** secondary outcomes were markers of a chronic systemic inflammatory response(ІL-6,ІL-8,and IFN-γ)and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention *** Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose ***,the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of *** with altered properties and pathogenic enterobacteria in patient *** the primary outcome analysis,improvements in the Stroop test parameters in all intervention groups were ***,EcN-treated patients performed 15%faster on the Stroop test than the lactulose group patients(P=0.017).Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ,IL-6 and *** was more efficient than lactulose in reducing proinflammatory cytokine ***

关键词： Hepatic encephalopathy Chronic liver disease cirrhosis Gut microbiota E.coli Nissle 1917 Cognitive functions Stroop test Rifaximin Lactulose

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