BackgroundAlcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative “shotgun” metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts—with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group.ResultsAlcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis—with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus—but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of functional potential, the patients showed different patterns of increase in functions related to alcohol metabolism and virulence factors, as well as pathways related to inflammation.ConclusionsMultiple shifts in the community structure and metabolic potential suggest strong negative influence of alcohol dependence and associated liver dysfunction on gut microbiota. The identified differences in patterns of impact between these two factors are important for planning of personalized treatment and prevention of these pathologies via microbiota modulation. Particularly, the expansion of Bifidobacterium and Lactobacillus suggests that probiotic interventions for patients with alcohol-related disorders using representatives of the same taxa should be considered with caution. Taxonomic and functional analysis shows an increased propensity of the gut microbiota to synthesis of the toxic acetaldehyde, suggesting higher risk of colorectal cancer and other pathologies in alcoholics.Electronic supplementary materialThe online version of this article (10.1...
The microbial community of the human gut has a crucial role in sustaining host homeostasis. High-throughput DNA sequencing has delineated the structural and functional configurations of gut metagenomes in world populations. The microbiota of the Russian population is of particular interest to researchers, because Russia encompasses a uniquely wide range of environmental conditions and ethnogeographical cohorts. Here we conduct a shotgun metagenomic analysis of gut microbiota samples from 96 healthy Russian adult subjects, which reveals novel microbial community structures. The communities from several rural regions display similarities within each region and are dominated by the bacterial taxa associated with the healthy gut. Functional analysis shows that the metabolic pathways exhibiting differential abundance in the novel types are primarily associated with the trade-off between the Bacteroidetes and Firmicutes phyla. The specific signatures of the Russian gut microbiota are likely linked to the host diet, cultural habits and socioeconomic status.
Aim of publication. To present indications for antihelicobacter therapy, methods and sequence of diagnostics and eradication treatment of Helicobacter pylori (H. pylori) infection to general practitioners. Key points. Chronic gastritis caused by H. pylori infection, including that in «asymptomatic» patients can be considered to be an indication for H. pylori eradication therapy both as etiological treatment and opportunistic screening diagnostics for gastric cancer prevention. Indications for obligatory antihelicobacter therapy include stomach and a duodenum peptic ulcer (PU), stomach MALT-lymphoma, early gastric cancer with endoscopic resection. Breath test with 13 С-labeled urea, laboratory test for assessment of anti-H. pylori antibodies in feces, rapid urease test and serological method can be recommended for primary diagnostics of infection. Serological test is not applicable after antihelicobacter therapy. According to the bulk of regional studies clarithromycin resistance level of H. pylori strains in Russia does not exceed 15%. Obtained data indicate the absence of high metronidazole-resistance of H. pylori as well as double resistance to clarithromycin and metronidazole. Standard triple therapy including proton pump inhibitor (PPI), clarithromycin and amoxicillin is recommended Цель публикации. Ознакомить практикующих врачей с показаниями к проведению антигеликобактерной терапии, методами и порядком проведения диагностики и эрадикационной терапии инфекции Helicobacter pylori (H. pylori). Основные положения. Хронический гастрит, вызванный инфекцией Н. pylori, в том числе у «бессимптомных» лиц, можно рассматривать как показание к проведению эрадикационной терапии инфекции Н. pylori в качестве этиотропного лечения и оппортунистического скрининга для профилактики рака желудка. Показаниями к обязательному проведению антигеликобактерной терапии служат язвенная болезнь желудка и двенадцатиперстной кишки, MALT-лимфома желудка, ранний рак желудка с эндоскопической резекцией. В качестве методов первичной диагностики инфекции H. pylori используют дыхательный тест с мочевиной, меченной 13 С, определение антигена H. pylori в кале лабораторным способом, быстрый уреазный тест и серологический метод. После проведения антигеликобактерной терапии серологический метод не применяют. Согласно результатам большинства региональных исследований, показатели устойчивости штаммов H. pylori к кларитромицину в России не выше
The human gut microbiome plays an important role both in health and disease. Use of antibiotics can alter gut microbiota composition, which can lead to various deleterious events. Here we report a whole genome sequencing metagenomic/genomic study of the intestinal microbiota changes caused by Helicobacter pylori (HP) eradication therapy. Using approaches for metagenomic data analysis we revealed a statistically significant decrease in alpha-diversity and relative abundance of Bifidobacterium adolescentis due to HP eradication therapy, while the relative abundance of Enterococcus faecium increased. We have detected changes in general metagenome resistome profiles as well: after HP eradication therapy, the ermB, CFX group, and tetQ genes were overrepresented, while tetO and tetW genes were underrepresented. We have confirmed these results with genome-resolved metagenomic approaches. MAG (metagenome-assembled genomes) abundance profiles have changed dramatically after HP eradication therapy. Focusing on ermB gene conferring resistance to macrolides, which were included in the HP eradication therapy scheme, we have shown a connection between antibiotic resistance genes (ARGs) and some overrepresented MAGs. Moreover, some E. faecium strains isolated from stool samples obtained after HP eradication have manifested greater antibiotic resistance in vitro in comparison to other isolates, as well as the higher number of ARGs conferring resistance to macrolides and tetracyclines.
Background Several studies have highlighted the role of host–microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), resulting in an increasing amount of data mainly focusing on Western patients. Because of the increasing prevalence of IBD in newly industrialized countries such as those in Asia, the Middle East, and South America, there is mounting interest in elucidating the gut microbiota of these populations. We present a comprehensive analysis of several IBD-related biomarkers and gut microbiota profiles and functions of a unique population of patients with IBD and healthy patients from Kazan (Republic of Tatarstan, Russia). Methods Blood and fecal IBD biomarkers, serum cytokines, and fecal short-chain fatty acid (SCFA) content were profiled. Finally, fecal microbiota composition was analyzed by 16S and whole-genome shotgun sequencing. Results Fecal microbiota whole-genome sequencing confirmed the presence of classic IBD dysbiotic features at the phylum level, with increased abundance of Proteobacteria, Actinobacteria, and Fusobacteria and decreased abundance of Firmicutes, Bacteroidetes, and Verrucomicrobia. At the genus level, the abundance of both fermentative (SCFA-producing and hydrogen (H2)-releasing) and hydrogenotrophic (H2-consuming) microbes was affected in patients with IBD. This imbalance was confirmed by the decreased abundance of SCFA species in the feces of patients with IBD and the change in anaerobic index, which mirrors the redox status of the intestine. Conclusions Our analyses highlighted how IBD-related dysbiotic microbiota—which are generally mainly linked to SCFA imbalance—may affect other important metabolic pathways, such as H2 metabolism, that are critical for host physiology and disease development.
The results of recent studies indicate a significant role of gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD). The aim of the study was to study the taxonomic and functional composition of the gut microbiota in ulcerative colitis (UC) and Crohn's disease (CD) patients to identify key markers of dysbiosis in IBD. Materials and methods. Fecal samples obtained from 95 IBD patients (78 UC and 17 CD) as well as 96 healthy volunteers were used for whole-genome sequencing carried out on the SOLiD 5500 W platform. Taxonomic profiling was performed by aligning the reeds, not maped on hg19, on MetaPhlAn2 reference database. Reeds were mapped using the HUNAnN2 algorithm to the ChocoPhlAn database to assess the representation of microbial metabolic pathways. Short-chain fatty acids (SCFA) level were measured in fecal samples by gas-liquid chromatographic analysis. Results and discussion. Changes in IBD patients gut microbiota were characterized by an increase in the representation of Proteobacteria and Bacteroidetes phyla bacteria and decrease in the number of Firmicutes phylum bacteria and Euryarchaeota phylum archaea; a decrease in the alpha-diversity index, relative representation of butyrate-producing, hydrogen-utilizing bacteria, and Methanobrevibacter smithii; increase in the relative representation of Ruminococcus gnavus in UC and CD patients and Akkermansia muciniphila in CD patients. Reduction of Butyryl-CoA: acetate CoA transferase gene relative representation in CD patients, decrease of absolute content of SCFA total number as well as particular SCFAs and main SCFAs ratio in IBD patients may indicate inhibition of functional activity and number of anaerobic microflora and/or an change in SCFA utilization by colonocytes. Conclusion: the revealed changes can be considered as typical signs of dysbiosis in IBD patients and can be used as potential targets for IBD patients personalized treatment development.
Актуальность обусловлена, с одной стороны, недостатком данных о распространенности в России Helicobacter pylori (HP), ассоцииро-ванного с риском развития язвенной болезни и рака желудка, и, с другой стороны, несоблю-дением врачами рекомендаций экспертов по диагностике этой инфекции и проведению эра-дикационной терапии. Цель -изучение распро-страненности НР у медицинских работников и их готовности пройти эрадикационную тера-пию. Материал и методы. Обследованы 315 ме-дицинских работников (61 мужчина и 254 жен-щины) в возрасте от 18 до 76 лет, в том числе в Москве -221, в Казани -94. Для определения инфицированности НР всем респондентам вы-полнен ¹³С-уреазный дыхательный тест с тест-на-бором «ХЕЛИКАРБ» по «четырехточечной» методике. Все участники заполнили анкеты, на основании анализа которых оценивалось вли-яние социальных и профессиональных факто-ров на распространенность НР. Результаты. НР выявлен у 54,9% обследованных: 45,9% мужчин и 57,1% женщин. Частота выявления НР в Москве существенно ниже (49,8%), чем в Казани (67%). Доля инфицированных НР нарастала с возрас-том: с 41,8% у лиц в возрасте до 25 лет до 76,9% в возрасте старше 60 лет. НР-позитивными были 60,2% состоящих в браке и 49% -не состоящих. В группе обследованных врачей наибольшая доля инфицированных наблюдалась среди эн-доскопистов (61,5%) и терапевтов (60,9%). Лишь 61,4% НР-позитивных медицинских работников выразили готовность к проведению эрадика-ционной терапии. Заключение. Проведенное исследование выявило высокую распростра-ненность НР у медработников, нарастающую с возрастом. Предположительно, это связано с гигиеническими условиями в детском возрасте каждого поколения, однако нельзя исключить возможность заражения в ходе профессиональ-ной деятельности. Ключевые слова:Helicobacter pylori, эпидемио-логия, инфицированность медицинских работ-ников, ¹³С-уреазный дыхательный тест, тест-на-бор «ХЕЛИКАРБ» Для цитирования: Бордин ДС, Плавник РГ, Невмержицкий ВИ, Буторова ЛИ, Абдулхаков РА, Абдулхаков СР, Войнован ИН, Эмбутниекс ЮВ. Распространенность Helicobacter pylori среди ме-дицинских работников Москвы и Казани по дан-ным ¹³С-уреазного дыхательного теста. Альманах клинической медицины. 2018;46(1):40-9.
Crohn's disease (CD) is a chronic inflammatory bowel disease that can be diagnosed at any age. There are two major patient groups based on diagnosis of this disease, before or after the age of 20 (juvenile/adolescent or adult), with disease progression in adults usually milder than in juvenile CD patients. Immune mechanisms have been suggested to play an important role in CD pathogenesis, with cytokines governing the development of the immune response. Upregulation of inflammatory cytokines in serum of juvenile and adult CD patients has been documented; still little is known about age-dependent differences in serum cytokine profiles of CD patients. We applied multiplex technology to analyze serum levels of 12 cytokines in juveniles and adults. We show that during the acute stage of the disease all CD patients have high serum levels of CXCL10, which remains upregulated during remission. Increased serum levels of TNF-α and IL-6 during the acute stage was characteristic of juvenile CD patients, whereas adult CD patients had upregulated levels of GM-CSF and IFN-γ. Taken together, these results demonstrate age-dependent differences in cytokine profiles, which may affect the pathogenesis of CD in patients at different ages of disease onset.
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