Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance

BACKGROUND:The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities. RESULTS:The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs. CONCLUSIONS:Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts. Video abstract

The Potential Roles of Extracellular Vesicles in Cigarette Smoke-Associated Diseases

Cigarette smoke contains more than 4,500 chemicals; most of which are highly reactive free radicals, which induce proinflammatory and carcinogenic reactions. Numerous efforts have focused extensively on the role of cigarette smoking as a cause of many diseases. Extracellular vesicles and exosomes have recently received increasing interest for their diagnostic and therapeutic roles in many diseases. However, research done on the role of extracellular vesicles and exosomes on cigarette smoke-induced chronic disease is still in its infancy. In this review, we summarize the recently addressed roles of extracellular vesicles and exosomes in the pathogenesis of cigarette smoke-related diseases, such as chronic obstructive pulmonary disease, cardiovascular disease, lung cancer, and oral cancer. Moreover, their potential utilization and future prospects as diagnostic biomarkers for cigarette smoke-related diseases are described. © 2018 A-Reum Ryu et al.1

Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of <it>Bifidobacterium adolescentis </it>isolated from healthy young Koreans.</p> <p>Methods</p> <p>The anti-proliferative activity of <it>B. adolescentis </it>isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of <it>B. adolescentis </it>SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line.</p> <p>Results</p> <p>The butanol extract of <it>B. adolescentis </it>SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of <it>B. adolescentis </it>SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells.</p> <p>Conclusion</p> <p>The butanol extract of <it>B. adolescentis </it>SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier.</p

Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçets disease

Background Behçets disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach. Methods Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs. Results Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2. Conclusions We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.This research was supported by the Bio & Medical Technology Develop‑ment Program of the NRF funded by the Korean government, MSIP [grant number 2014M3A9B6069341], and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea [grant numbers HU20C0187]

Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content

<p>Abstract</p> <p>Background</p> <p>Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether <it>Bifidobacteria </it>isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content.</p> <p>Methods</p> <p><it>In vitro </it>culture experiments were performed to evaluate the ability of <it>Bifidobacterium </it>spp. isolated from healthy Koreans (20~30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (10⁸~10⁹CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks.</p> <p>Results</p> <p><it>B. longum </it>SPM1207 reduced serum total cholesterol and LDL levels significantly (<it>p </it>< 0.05), and slightly increased serum HDL. <it>B. longum </it>SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities.</p> <p>Conclusion</p> <p>Daily consumption of <it>B. longum </it>SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation.</p

Human AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability

The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease (APE) participates in the repair of AP sites in the cellular DNA as well as participating in the redox regulation of the transcription factor function. The function of APE is considered as the rate-limiting step in DNA base excision repair. Paradoxically, an unbalanced increase in APE protein leads to genetic instability. Therefore, we investigated the mechanisms of genetic instability that are induced by APE. Here, we report that the overexpression of APE protein disrupts the repair of DNA mismatches, which results in microsatellite instability (MSI). We found that expression of APE protein led to the suppression of the repair of DNA mismatches in the normal human fibroblast cells. Western blot analysis revealed that hMSH6 protein was markedly reduced in the APE-expressing cells. Moreover, the addition of purified Mutα (MSH2 and MSH6 complex) to the extracts from the APE-expressing cells led to the restoration of mismatch repair (MMR) activity. By performing MMR activity assay and MSI analysis, we found that the co-expression of hMSH6 and APE exhibited the microsatellite stability, whereas the expression of APE alone generated the MSI-high phenotype. The APE-mediated decrease in MMR activity described here demonstrates the presence of a new and highly effective APE-mediated mechanism for MSI