group leader: Prof. Pieper

Recent Submissions

  • The Role of Pulmonary and Systemic Immunosenescence in Acute Lung Injury.

    Brandenberger, Christina; Kling, Katharina Maria; Vital, Marius; Christian, Mühlfeld; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-08-01)
    Acute lung injury (ALI) is associated with increased morbidity and mortality in the elderly (> 65 years), but the knowledge about origin and effects of immunosenescence in ALI is limited. Here, we investigated the immune response at pulmonary, systemic and cellular level in young (2-3 months) and old (18-19 months) C57BL/6J mice to localize and characterize effects of immunosenescence in ALI. ALI was induced by intranasal lipopolysaccharide (LPS) application and the animals were sacrificed 24 or 72 h later. Pulmonary inflammation was investigated by analyzing histopathology, bronchoalveolar lavage fluid (BALF) cytometry and cytokine expression. Systemic serum cytokine expression, spleen lymphocyte populations and the gut microbiome were analyzed, as well as activation of alveolar and bone marrow derived macrophages (BMDM)
  • Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessary-clinical study and microbiota analysis.

    Gottschick, Cornelia; Deng, Zhi-Luo; Vital, Marius; Masur, Clarissa; Abels, Christoph; Pieper, Dietmar H; Rohde, Manfred; Mendling, Werner; Wagner-Döbler, Irene; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-13)
    Bacterial vaginosis (BV) is the most common vaginal syndrome among women in their reproductive years. It is associated with an increased risk of acquiring sexually transmitted infections and complications like preterm labor. BV is characterized by a high recurrence rate for which biofilms frequently found on vaginal epithelial cells may be a reason. Here, we report a controlled randomized clinical trial that tested the safety and effectiveness of a newly developed pessary containing an amphoteric tenside (WO3191) to disrupt biofilms after metronidazole treatment of BV. Pessaries containing lactic acid were provided to the control group, and microbial community composition was determined via Illumina sequencing of the V1-V2 region of the 16S rRNA gene. The most common community state type (CST) in healthy women was characterized by Lactobacillus crispatus. In BV, diversity was high with communities dominated by either Lactobacillus iners, Prevotella bivia, Sneathia amnii, or Prevotella amnii. Women with BV and proven biofilms had an increased abundance of Sneathia sanguinegens and a decreased abundance of Gardnerella vaginalis. Following metronidazole treatment, clinical symptoms cleared, Nugent score shifted to Lactobacillus dominance, biofilms disappeared, and diversity (Shannon index) was reduced in most women. Most of the patients responding to therapy exhibited a L. iners CST. Treatment with WO 3191 reduced biofilms but did not prevent recurrence. Women with high diversity after antibiotic treatment were more likely to develop recurrence. Stabilizing the low diversity healthy flora by promoting growth of health-associated Lactobacillus sp. such as L. crispatus may be beneficial for long-term female health. NCT02687789.
  • Chronic rhinosinusitis with nasal polyps is characterized by dysbacteriosis of the nasal microbiota.

    Chalermwatanachai, Thanit; Vilchez-Vargas, Ramiro; Holtappels, Gabriele; Lacoere, Tim; Jáuregui, Ruy; Kerckhof, Frederiek-Maarten; Pieper, Dietmar H; Van de Wiele, Tom; Vaneechoutte, Mario; Van Zele, Thibaut; Bachert, Claus; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-21)
    Chronic rhinosinusitis with nasal polyp (CRSwNP) patients are often characterized by asthma comorbidity and a type-2 inflammation of the sinonasal mucosa. The mucosal microbiota has been suggested to be implicated in the persistence of inflammation, but associations have not been well defined. To compare the bacterial communities of healthy subjects with CRSwNP patients, we collected nasal swabs from 17 healthy subjects, 21 CRSwNP patients without asthma (CRSwNP-A), and 20 CRSwNP patients with co-morbid asthma (CRSwNP+A). We analysed the microbiota using high-throughput sequencing of the bacterial 16S rRNA. Bacterial communities were different between the three groups. Haemophilus influenzae was significantly enriched in CRSwNP patients, Propionibacterium acnes in the healthy group; Staphylococcus aureus was abundant in the CRSwNP-A group, even though present in 57% of patients. Escherichia coli was found in high amounts in CRSwNP+A patients. Nasal tissues of CRSwNP+A patients expressed significantly higher concentrations of IgE, SE-IgE, and IL-5 compared to those of CRSwNP-A patients. Co-cultivation demonstrated that P. acnes growth was inhibited by H. influenzae, E. coli and S. aureus. The nasal microbiota of healthy subjects are different from those of CRSwNP-A and CRSwNP+A patients. However, the most abundant species in healthy status could not inhibit those in CRSwNP disease.
  • Detection of Streptococcus pyogenes virulence genes in Streptococcus dysgalactiae subsp. equisimilis from Vellore, India.

    Babbar, Anshu; Itzek, Andreas; Pieper, Dietmar H; Nitsche-Schmitz, D Patric; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-03-12)
    Streptococcus dysgalactiae subsp. equisimilis (SDSE), belonging to the group C and G streptococci, are human pathogens reported to cause clinical manifestations similar to infections caused by Streptococcus pyogenes. To scrutinize the distribution of gene coding for S. pyogenes virulence factors in SDSE, 255 isolates were collected from humans infected with SDSE in Vellore, a region in southern India, with high incidence of SDSE infections. Initial evaluation indicated SDSE isolates comprising of 82.35% group G and 17.64% group C. A multiplex PCR system was used to detect 21 gene encoding virulence-associated factors of S. pyogenes, like superantigens, DNases, proteinases, and other immune modulatory toxins. As validated by DNA sequencing of the PCR products, sequences homologous to speC, speG, speH, speI, speL, ssa and smeZ of the family of superantigen coding genes and for DNases like sdaD and sdc were detected in the SDSE collection. Furthermore, there was high abundance (48.12% in group G and 86.6% in group C SDSE) of scpA, the gene coding for C5a peptidase in these isolates. Higher abundance of S. pyogenes virulence factor genes was observed in SDSE of Lancefield group C as compared to group G, even though the incidence rates in former were lower. This study not only substantiates detection of S. pyogenes virulence factor genes in whole genome sequenced SDSE but also makes significant contribution towards the understanding of SDSE and its increasing virulence potential.
  • Insights into Broilers' Gut Microbiota Fed with Phosphorus, Calcium, and Phytase Supplemented Diets.

    Borda-Molina, Daniel; Vital, Marius; Sommerfeld, Vera; Rodehutscord, Markus; Camarinha-Silva, Amélia; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
    Phytase supplementation in broiler diets is a common practice to improve phosphorus (P) availability and to reduce P loss by excretion. An enhanced P availability, and its concomitant supplementation with calcium (Ca), can affect the structure of the microbial community in the digestive tract of broiler chickens. Here, we aim to distinguish the effects of mineral P, Ca, and phytase on the composition of microbial communities present in the content and the mucosa layer of the gastrointestinal tract (GIT) of broiler chickens. Significant differences were observed between digesta and mucosa samples for the GIT sections studied (p= 0.001). The analyses of 56 individual birds showed a high microbial composition variability within the replicates of the same diet. The average similarity within replicates of digesta and mucosa samples across all diets ranged from 29 to 82% in crop, 19-49% in ileum, and 17-39% in caeca. Broilers fed with a diet only supplemented with Ca had the lowest body weight gain and feed conversion values while diets supplemented with P showed the best performance results. An effect of each diet on crop mucosa samples was observed, however, similar results were not obtained from digesta samples. Microbial communities colonizing the ileum mucosa samples were affected by P supplementation. Caeca-derived samples showed the highest microbial diversity when compared to the other GIT sections and the most prominent phylotypes were related to genusFaecalibacteriumandPseudoflavonifractor, known for their influence on gut health and as butyrate producers. Lower microbial diversity in crop digesta was linked to lower growth performance of birds fed with a diet only supplemented with Ca. Each diet affected microbial communities within individual sections, however, no diet showed a comprehensive effect across all GIT sections, which can primarily be attributed to the great variability among replicates. The substantial community differences between digesta and mucosa derived samples indicate that both habitats have to be considered when the influence of diet on the gut microbiota, broiler growth performance, and animal health is investigated.
  • Members of a new subgroup of Streptococcus anginosus harbor virulence related genes previously observed in Streptococcus pyogenes.

    Babbar, Anshu; Kumar, Venkatesan Naveen; Bergmann, René; Barrantes, Israel; Pieper, Dietmar H; Itzek, Andreas; Nitsche-Schmitz, D Patric; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-04)
    Conventionally categorized as commensals, the Streptococci of the species S. anginosus are facultative human pathogens that are difficult to diagnose and often overlooked. Furthermore, detailed investigation and diagnosis of S. anginosus infections is hampered by unexplored taxonomy and widely elusive molecular pathogenesis. To explore their pathogenic potential, S. anginosus isolates collected from patients of two geographical locations (Vellore, India and Leipzig, Germany) were subjected to multi-locus sequence analysis (MLSA). This analysis revealed the potential presence of a new distinct clade of the species S. anginosus, tentatively termed here as genomosubspecies vellorensis. A complementary PCR-based screening for S. pyogenes virulence factor as well as antibiotic resistance genes revealed not only the presence of superantigen- and extracellular DNase coding genes identical to corresponding genes of S. pyogenes, but also of erythromycin and tetracycline resistance genes in the genomes of the analyzed S. anginosus isolates, thus posing a matter of significant health concern. Identification of new pathogenic S. anginosus strains capable of causing difficult to treat infections may pose additional challenges to the diagnosis and treatment of Streptococcus based infections.
  • Initial evenness determines diversity and cell density dynamics in synthetic microbial ecosystems.

    Ehsani, Elham; Hernandez-Sanabria, Emma; Kerckhof, Frederiek-Maarten; Props, Ruben; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar Helmut; Boon, Nico; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-10)
    The effect of initial evenness on the temporal trajectory of synthetic communities in comprehensive, low-volume microcosm studies remains unknown. We used flow cytometric fingerprinting and 16S rRNA gene amplicon sequencing to assess the impact of time on community structure in one hundred synthetic ecosystems of fixed richness but varying initial evenness. Both methodologies uncovered a similar reduction in diversity within synthetic communities of medium and high initial evenness classes. However, the results of amplicon sequencing showed that there were no significant differences between and within the communities in all evenness groups at the end of the experiment. Nevertheless, initial evenness significantly impacted the cell density of the community after five medium transfers. Highly even communities retained the highest cell densities at the end of the experiment. The relative abundances of individual species could be associated to particular evenness groups, suggesting that their presence was dependent on the initial evenness of the synthetic community. Our results reveal that using synthetic communities for testing ecological hypotheses requires prior assessment of initial evenness, as it impacts temporal dynamics.
  • The Inner Workings of the Outer Surface: Skin and Gill Microbiota as Indicators of Changing Gut Health in Yellowtail Kingfish.

    Legrand, Thibault P R A; Catalano, Sarah R; Wos-Oxley, Melissa L; Stephens, Fran; Landos, Matt; Bansemer, Matthew S; Stone, David A J; Qin, Jian G; Oxley, Andrew P A; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
    The mucosal surfaces and associated microbiota of fish are an important primary barrier and provide the first line of defense against potential pathogens. An understanding of the skin and gill microbial assemblages and the factors which drive their composition may provide useful insights into the broad dynamics of fish host-microbial relationships, and may reveal underlying changes in health status. This is particularly pertinent to cultivated systems whereby various stressors may led to conditions (like enteritis) which impinge on productivity. As an economically important species, we assessed whether the outer-surface bacterial communities reflect a change in gut health status of cultivated Yellowtail Kingfish (Seriola lalandi). Active bacterial assemblages were surveyed from RNA extracts from swabs of the skin and gills by constructing Illumina 16S rRNA gene amplicon libraries. Proteobacteria and Bacteroidetes were predominant in both the skin and gills, with enrichment of key β-proteobacteria in the gills (Nitrosomonadales and Ferrovales). Fish exhibiting early stage chronic lymphocytic enteritis comprised markedly different global bacterial assemblages compared to those deemed healthy and exhibiting late stages of the disease. This corresponded to an overall loss of diversity and enrichment of Proteobacteria and Actinobacteria, particularly in the gills. In contrast, bacterial assemblages of fish with late stage enteritis were generally similar to those of healthy individuals, though with some distinct taxa. In conclusion, gut health status is an important factor which defines the skin and gill bacterial assemblages of fish and likely reflects changes in immune states and barrier systems during the early onset of conditions like enteritis. This study represents the first to investigate the microbiota of the outer mucosal surfaces of fish in response to underlying chronic gut enteritis, revealing potential biomarkers for assessing fish health in commercial aquaculture systems.
  • Colonic Butyrate-Producing Communities in Humans: an Overview Using Omics Data.

    Vital, Marius; Karch, André; Pieper, Dietmar H.; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2018-01-18)
    Given the key role of butyrate for host health, understanding the ecology of intestinal butyrate-producing communities is a top priority for gut microbiota research. To this end, we performed a pooled analysis on 2,387 metagenomic/transcriptomic samples from 15 publicly available data sets that originated from three continents and encompassed eight diseases as well as specific interventions. For analyses, a gene catalogue was constructed from gene-targeted assemblies of all genes from butyrate synthesis pathways of all samples and from an updated reference database derived from genome screenings. We demonstrate that butyrate producers establish themselves within the first year of life and display high abundances (>20% of total bacterial community) in adults regardless of origin. Various bacteria form this functional group, exhibiting a biochemical diversity including different pathways and terminal enzymes, where one carbohydrate-fueled pathway was dominant with butyryl coenzyme A (CoA):acetate CoA transferase as the main terminal enzyme. Subjects displayed a high richness of butyrate producers, and 17 taxa, primarily members of the Lachnospiraceae and Ruminococcaceae along with some Bacteroidetes, were detected in >70% of individuals, encompassing ~85% of the total butyrate-producing potential. Most of these key taxa were also found to express genes for butyrate formation, indicating that butyrate producers occupy various niches in the gut ecosystem, concurrently synthesizing that compound. Furthermore, results from longitudinal analyses propose that diversity supports functional stability during ordinary life disturbances and during interventions such as antibiotic treatment. A reduction of the butyrate-producing potential along with community alterations was detected in various diseases, where patients suffering from cardiometabolic disorders were particularly affected. IMPORTANCE Studies focusing on taxonomic compositions of the gut microbiota are plentiful, whereas its functional capabilities are still poorly understood. Specific key functions deserve detailed investigations, as they regulate microbiota-host interactions and promote host health and disease. The production of butyrate is among the top targets since depletion of this microbe-derived metabolite is linked to several emerging noncommunicable diseases and was shown to facilitate establishment of enteric pathogens by disrupting colonization resistance. In this study, we established a workflow to investigate in detail the composition of the polyphyletic butyrate-producing community from omics data extracting its biochemical and taxonomic diversity. By combining information from various publicly available data sets, we identified universal ecological key features of this functional group and shed light on its role in health and disease. Our results will assist the development of precision medicine to combat functional dysbiosis.
  • In vitro colonisation of the distal colon by Akkermansia muciniphila is largely mucin and pH dependent.

    Van Herreweghen, F; Van den Abbeele, P; De Mulder, T; De Weirdt, R; Geirnaert, A; Hernandez-Sanabria, E; Vilchez-Vargas, R; Jauregui, R; Pieper, D H; Belzer, C; De Vos, W M; Van de Wiele, T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-02-07)
    Host mucin is the main constituent of the mucus layer that covers the gut epithelium of the host, and an important source of glycans for the bacteria colonising the intestine. Akkermansia muciniphila is a mucin-degrading bacterium, abundant in the human gut, that is able to produce acetate and propionate during this degradation process. A. muciniphila has been correlated with human health in previous studies, but a mechanistic explanation is lacking. In this study, the main site of colonisation was characterised alongside additional conditions, such as differences in colon pH, prebiotic supplementation and variable mucin supply. To overcome the limitations of in vivo studies concerning variations in mucin availability and difficult access to proximal regions of the colon, a dynamic in vitro gut model (SHIME) was used. In this model, A. muciniphila was found to colonise the distal colon compartment more abundantly than the proximal colon ((±8 log copies/ml compared to ±4 log copies/ml) and the preference for the distal compartment was found to be pH-dependent. The addition of mucin caused a specific increase of A. muciniphila (±4.5 log increase over two days), far exceeding the response of other bacteria present, together with an increase in propionate. These findings suggest that colonisation and mucin degradation by A. muciniphila is dependent on pH and the concentration of mucin. Our results revealed the preference of A. muciniphila for the distal colon environment due to its higher pH and uncovered the quick and stable response of A. muciniphila to mucin supplementation.
  • High-fiber and high-protein diets shape different gut microbial communities, which ecologically behave similarly under stress conditions, as shown in a gastrointestinal simulator.

    Marzorati, Massimo; Vilchez-Vargas, Ramiro; Bussche, Julie Vanden; Truchado, Pilar; Jauregui, Ruy; El Hage, Racha Ahmad; Pieper, Dietmar H; Vanhaecke, Lynn; Van de Wiele, Tom; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-01)
    The aim of this work was to investigate the relationship between the structure of gut microbial communities fed with different diets (i.e. high-protein-HP- versus high-fiber-HF-diet) and their functional stability when challenged with mild and acute doses of a mix of amoxicillin, ciprofloxacin, and tetracycline. We made use of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®)-a continuous model of the gastrointestinal tract-coupled with 16S-targeted Illumina and metabolomics (i.e. UHPLC-HRMS) analyses. Independently of the diet, the sudden exposure to an acute stress led to a modification of the microbial community structure, selecting for species belonging to Bacillus spp.; Clostridium cluster XIVa; Enterococci; Bacteroides; and Enterobacteriaceae. The antibiotic treatment led to a decrease in the number of operational taxonomic units (at least -10%). Cluster analysis of untargeted metabolic data showed that the antibiotic treatment affected the microbial activity. The impact on metabolites production was lower when the community was preexposed to mild doses of the antibiotic mix. This effect was stronger in the proximal colon for the HF diet and in the distal colon for the HP diet. Different diets shaped different gut microbial communities, which ecologically behaved similarly under stress conditions.
  • Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessary-clinical study and microbiota analysis.

    Gottschick, Cornelia; Deng, Zhi-Luo; Vital, Marius; Masur, Clarissa; Abels, Christoph; Pieper, Dietmar H; Rohde, Manfred; Mendling, Werner; Wagner-Döbler, Irene; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-13)
    Bacterial vaginosis (BV) is the most common vaginal syndrome among women in their reproductive years. It is associated with an increased risk of acquiring sexually transmitted infections and complications like preterm labor. BV is characterized by a high recurrence rate for which biofilms frequently found on vaginal epithelial cells may be a reason.
  • Functional soil metagenomics: elucidation of polycyclic aromatic hydrocarbon degradation potential following 12 years of in situ bioremediation.

    Duarte, Márcia; Nielsen, Agnes; Camarinha-Silva, Amélia; Vilchez-Vargas, Ramiro; Bruls, Thomas; Wos-Oxley, Melissa L; Jauregui, Ruy; Pieper, Dietmar H.; Helmholtz Centre for infection research GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-08)
    A culture-independent function-based screening approach was used to assess the microbial aerobic catabolome for polycyclic aromatic hydrocarbons degradation of a soil subjected to 12 years of in situ bioremediation. A total of 422 750 fosmid clones were screened for key aromatic ring-cleavage activities using 2,3-dihydroxybiphenyl as substrate. Most of the genes encoding ring-cleavage enzymes on the 768 retrieved positive fosmids could not be identified using primer-based approaches and, thus, 205 fosmid inserts were sequenced. Nearly two hundred extradiol dioxygenase encoding genes of three different superfamilies could be identified. Additional key genes of aromatic metabolic pathways were identified, including a high abundance of Rieske non-heme iron oxygenases that provided detailed information on enzymes activating aromatic compounds and enzymes involved in activation of the side chain of methylsubstituted aromatics. The gained insights indicated a complex microbial network acting at the site under study, which comprises organisms similar to recently identified Immundisolibacter cernigliae TR3.2 and Rugosibacter aromaticivorans Ca6 and underlined the great potential of an approach that combines an activity-screening, a cost-effective high-throughput sequencing of fosmid clones and a phylogenomic-routed and manually curated database to carefully identify key proteins dedicated to aerobic degradation of aromatic compounds.
  • Uncovering the trimethylamine-producing bacteria of the human gut microbiota.

    Rath, Silke; Heidrich, Benjamin; Pieper, Dietmar H; Vital, Marius; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-05-15)
    Trimethylamine (TMA), produced by the gut microbiota from dietary quaternary amines (mainly choline and carnitine), is associated with atherosclerosis and severe cardiovascular disease. Currently, little information on the composition of TMA producers in the gut is available due to their low abundance and the requirement of specific functional-based detection methods as many taxa show disparate abilities to produce that compound.
  • [Intestinal microbiota in individualized therapies].

    Witte, T; Pieper, D H; Heidrich, B; Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany. (2017-05-24)
    During recent years, the analysis of the human microbiota has been receiving more and more scientific focus. Deep sequencing analysis enables characterization of microbial communities in different environments without the need of culture-based methods. Hereby, information about microbial communities is increasing enormously. Numerous studies in humans and animal models revealed the important role of the microbiome in emergence and natural course of diseases such as autoimmune diseases and metabolic disorders, e. g., the metabolic syndrome. The identification of causalities between the intestinal microbiota composition and function, and diseases in humans and animal models can help to develop individualized therapies targeting the microbiome and its modification. Nowadays, it is established that several factors influence the composition of the microbiota. Diet it is one of the major factors shaping the microbiota and the use of pro- and prebiotica may induce changes in the microbial community. Fecal microbiome transfer is the first approach targeting the intestinal microbiota which is implemented in the clinical routine for patients with therapy-refractory infections with Clostridium difficile. Herewith, the recipient's microbiota can be changed permanently and the patient can be cured from the infection.
  • Association between cytokine response, the LRINEC score and outcome in patients with necrotising soft tissue infection: a multicentre, prospective study.

    Hansen, Marco Bo; Rasmussen, Lars Simon; Svensson, Mattias; Chakrakodi, Bhavya; Bruun, Trond; Madsen, Martin Bruun; Perner, Anders; Garred, Peter; Hyldegaard, Ole; Norrby-Teglund, Anna; Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany. (2017-02-08)
    Early assessment of necrotising soft tissue infection (NSTI) is challenging. Analysis of inflammatory markers could provide important information about disease severity and guide decision making. For this purpose, we investigated the association between cytokine levels and the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC)-score, disease severity and mortality in NSTI patients. In 159 patients, plasma was analysed for IL-1β, IL-6, IL-10 and TNF-α upon admission. The severity of NSTI was assessed by SAPS, SOFA score, septic shock, microbial aetiology, renal replacement therapy and amputation. We found no significant difference in cytokine levels according to a LRINEC- score above or below 6 (IL-1β: 3.0 vs. 1.3; IL-6: 607 vs. 289; IL-10: 38.4 vs. 38.8; TNF-α: 15.1 vs. 7.8 pg/mL, P > 0.05). Patients with β-haemolytic streptococcal infection had higher level of particularly IL-6. There was no difference in mortality between patients with a LRINEC-score above or below 6. In the adjusted analysis assessing 30-day mortality, the association was strongest for IL-1β (OR 3.86 [95% CI, 1.43-10.40], P = 0.008) and IL-10 (4.80 [1.67-13.78], P = 0.004). In conclusion, we found no significant association between the LRINEC-score and cytokine levels on admission. IL-6 was consistently associated with disease severity, whereas IL-1β had the strongest association with 30-day mortality.
  • Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort.

    Akmatov, Manas K; Koch, Nadine; Vital, Marius; Ahrens, Wolfgang; Flesch-Janys, Dieter; Fricke, Julia; Gatzemeier, Anja; Greiser, Halina; Günther, Kathrin; Illig, Thomas; Kaaks, Rudolf; Krone, Bastian; Kühn, Andrea; Linseisen, Jakob; Meisinger, Christine; Michels, Karin; Moebus, Susanne; Nieters, Alexandra; Obi, Nadia; Schultze, Anja; Six-Merker, Julia; Pieper, Dietmar H; Pessler, Frank; TWINCORE; Zentrum für experimentelle und klinische Infectionsforsching GmbH, Feodor-Lynen Str. 17, 30625 Hannover, Germany. (2017-05-12)
    We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.
  • Draft Genome Sequence of Streptococcus dysgalactiae subsp. equisimilis Strain C161L1 Isolated in Vellore, India.

    Babbar, Anshu; Nitsche-Schmitz, D Patric; Pieper, Dietmar H; Barrantes, Israel; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-05-11)
    Streptococcus dysgalactiae subsp. equisimilis belongs to the β-hemolytic group C and G pyogenic group of streptococci. Here, we report the draft genome of the S. dysgalactiae subsp. equisimilis strain C161L1 from Vellore, a region in southern India with a high incidence rate of S. dysgalactiae subsp. equisimilis infection. This genome is 2.1 Mb long, with a 39.82% G+C content, and encodes 2,022 genes.
  • Microbial communities in pyrene amended soil-compost mixture and fertilized soil.

    Adam, Iris K U; Duarte, Márcia; Pathmanathan, Jananan; Miltner, Anja; Brüls, Thomas; Kästner, Matthias; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-12)
    Polycyclic aromatic hydrocarbons are distributed ubiquitously in the environment and form metabolites toxic to most organisms. Organic amendment of PAH contaminated soil with compost and farmyard manure has proven to be efficient for PAH bioremediation mediated by native microorganisms, even though information on the identity of PAH degraders in organic-amended soil is still scarce. Here we provide molecular insight into the bacterial communities in soil amended with compost or farmyard manure for which the degradation mass balances of (13)C-labeled pyrene have been recently published and assess the relevant bacterial genera capable of degrading pyrene as a model PAH. We performed statistical analyses of bacterial genera abundance data based on total DNA and RNA (for comparison) extracted from the soil samples. The results revealed complex pyrene degrading communities with low abundance of individual degraders instead of a limited number of abundant key players. The bacterial degrader communities of the soil-compost mixture and soil fertilized with farmyard manure differed considerably in composition albeit showing similar degradation kinetics. Additional analyses were carried out on enrichment cultures and enabled the reconstruction of several nearly complete genomes, thus allowing to link microcosm and enrichment experiments. However, pyrene mineralizing bacteria enriched from the compost or unfertilized soil-compost samples did not dominate pyrene degradation in the soils. Based on the present findings, evaluations of PAH degrading microorganisms in complex soil mixtures with high organic matter content should not target abundant key degrading species, since the specific degraders may be highly diverse, of low abundance, and masked by high bacterial background.
  • Ursodeoxycholic acid and its taurine/glycine conjugated species reduce colitogenic dysbiosis and equally suppress experimental colitis in mice.

    Van den Bossche, Lien; Hindryckx, Pieter; Devisscher, Lindsey; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H; Vanden Bussche, Julie; Vanhaecke, Lynn; Van de Wiele, Tom; De Vos, Martine; Laukens, Debby; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-01-23)
    The promising results with secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine/glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA) or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and improve inflammation in human IBD.

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