• Bacterial community structure and effects of picornavirus infection on the anterior nares microbiome in early childhood.

      Caputo, Mahrrouz; Zoch-Lesniak, Beate; Karch, André; Vital, Marius; Meyer, Frederic; Klawonn, Frank; Baillot, Armin; Pieper, Dietmar H; Mikolajczyk, Rafael T; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2019-01-07)
      Little is known regarding the nasal microbiome in early childhood and the impact of respiratory infection on the infants' nasal microbial composition. Here we investigated the temporal dynamics and diversity of the bacterial composition in the anterior nares in children attending daycare centers. For our investigation, we considered 76 parental-taken nasal swabs of 26 children (aged 13 to 36 months) collected over a study period of 3 months. Overall, there was no significant age-specific effect or seasonal shift in the nasal bacterial community structure. In a sub-sample of 14 healthy children the relative abundance of individual taxa as well as the overall diversity did not reveal relevant changes, indicating a stable community structure over the entire study period. Moreover, the nasal bacterial profiles clustered subject-specific with Bray-Curtis similarities being elevated in intra-subject calculations compared to between-subject calculations. The remaining subset of 12 children provided samples taken during picornavirus infection (PVI) and either before or after a PVI. We detected an association between the relative abundance of members of the genus Streptococcus and PV when comparing both (i) samples taken during PVI with samples out of 14 healthy children and (ii) samples taken during PVI with samples taken after PVI within the same individual. In addition, the diversity was higher during PVI than after infection. Our findings suggest that a personalized structure of the nasal bacterial community is established already in early childhood and could be detected over a timeframe of 3 months. Studies following infants over a longer time with frequent swab sampling would allow investigating whether certain parameter of the bacterial community, such as the temporal variability, could be related to viral infection.
    • 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.
    • Pathogenic functions of host microbiota.

      Rath, Silke; Rud, Tatjana; Karch, André; Pieper, Dietmar Helmut; Vital, Marius; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-09-28)
      It is becoming evident that certain features of human microbiota, encoded by distinct autochthonous taxa, promote disease. As a result, borders between the so-called opportunistic pathogens, pathobionts, and commensals are increasingly blurred, and specific targets for manipulating microbiota to improve host health are becoming elusive. In this study, we focus on the functions of host bacterial communities that have the potential to cause disease, proposing the term "pathogenic function (pathofunction)". The concept is presented via three distinct examples, namely, the formation of (i) trimethylamine, (ii) secondary bile acids, and (iii) hydrogen sulfide, which represent metabolites of the gut microbiota linked to the development of non-communicable diseases. Using publicly available metagenomic and metatranscriptomic data (n = 2975), we quantified those pathofunctions in health and disease and exposed the key players. Pathofunctions were ubiquitously present with increased abundances in patient groups. Overall, the three pathofunctions were detected at low mean concentrations (< 1% of total bacteria carried respective genes) and encompassed various taxa, including uncultured members. We outline how this function-centric approach, where all members of a community exhibiting a particular pathofunction are redundant, can contribute to risk assessment and the development of precision treatment directing gut microbiota to increase host health.