In vitro modeling of bile acid processing by the human fecal microbiota

Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers (n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia. This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches, coupled to in vitro model systems, to study the biochemical capabilities of bacteria within complex ecosystems. Characterizing the dynamic interactions between the gut microbiota and the bile acid pool enables a greater understanding of how variation in the gut microbiota influences host bile acid signatures, their associated functions and their implications for health

The domestication of the probiotic bacterium Lactobacillus acidophilus

Lactobacillus acidophilus is a Gram-positive lactic acid bacterium that has had widespread historical use in the dairy industry and more recently as a probiotic. Although L. acidophilus has been designated as safe for human consumption, increasing commercial regulation and clinical demands for probiotic validation has resulted in a need to understand its genetic diversity. By drawing on large, well-characterised collections of lactic acid bacteria, we examined L. acidophilus isolates spanning 92 years and including multiple strains in current commercial use. Analysis of the whole genome sequence data set (34 isolate genomes) demonstrated L. acidophilus was a low diversity, monophyletic species with commercial isolates essentially identical at the sequence level. Our results indicate that commercial use has domesticated L. acidophilus with genetically stable, invariant strains being consumed globally by the human population

Star-forming galaxies versus low- and high-excitation radio AGN in the VLA-COSMOS 3GHz Large Project

We study the composition of the faint radio population selected from the VLA-COSMOS 3GHz Large Project, a radio continuum survey performed at 10 cm wavelength. The survey covers the full 2 square degree COSMOS field with mean $rms\sim2.3$ $\mu$Jy/beam, cataloging 10,899 source components above $5\times rms$. By combining these radio data with UltraVISTA, optical, near-infrared, and Spitzer/IRAC mid-infrared data, as well as X-ray data from the Chandra Legacy, and Chandra COSMOS surveys, we gain insight into the emission mechanisms within our radio sources out to redshifts of $z\sim5$. From these emission characteristics we classify our souces as star forming galaxies or AGN. Using their multi-wavelength properties we further separate the AGN into sub-samples dominated by radiatively efficient and inefficient AGN, often referred to as high- and low-excitation emission line AGN. We compare our method with other results based on fitting of the sources' spectral energy distributions using both galaxy and AGN spectral models, and those based on the infrared-radio correlation. We study the fractional contributions of these sub-populations down to radio flux levels of $\sim$10 $\mu$Jy. We find that at 3 GHz flux densities above $\sim$400 $\mu$Jy quiescent, red galaxies, consistent with the low-excitation radio AGN class constitute the dominant fraction. Below densities of $\sim$200 $\mu$Jy star-forming galaxies begin to constitute the largest fraction, followed by the low-excitation, and X-ray- and IR-identified high-excitation radio AGN.Comment: 7 pages, 3 figures, The many facets of extragalactic radio surveys: towards new scientific challenges, Bologna 20-23 October 201

Inferring Compton-thick AGN candidates at z>2 with Chandra using the >8 keV restframe spectral curvature

To fully understand cosmic black hole growth we need to constrain the population of heavily obscured active galactic nuclei (AGN) at the peak of cosmic black hole growth ($z\sim$1-3). Sources with obscuring column densities higher than $\mathrm{10^{24}}$ atoms $\mathrm{cm^{-2}}$, called Compton-thick (CT) AGN, can be identified by excess X-ray emission at $\sim$20-30 keV, called the "Compton hump". We apply the recently developed Spectral Curvature (SC) method to high-redshift AGN (2<z<5) detected with Chandra. This method parametrizes the characteristic "Compton hump" feature cosmologically redshifted into the X-ray band at observed energies <10 keV. We find good agreement in CT AGN found using the SC method and bright sources fit using their full spectrum with X-ray spectroscopy. In the Chandra deep field south, we measure a CT fraction of $\mathrm{17^{+19}_{-11}\%}$ (3/17) for sources with observed luminosity $\mathrm{>5\times 10^{43}}$ erg $\mathrm{s^{-1}}$. In the Cosmological evolution survey (COSMOS), we find an observed CT fraction of $\mathrm{15^{+4}_{-3}\%}$ (40/272) or $\mathrm{32\pm11 \%}$ when corrected for the survey sensitivity. When comparing to low redshift AGN with similar X-ray luminosities, our results imply the CT AGN fraction is consistent with having no redshift evolution. Finally, we provide SC equations that can be used to find high-redshift CT AGN (z>1) for current (XMM-Newton) and future (eROSITA and ATHENA) X-ray missions.Comment: 10 pages, 8 figure

Disseminated Mycobacterium avium infection in a cat on long-term ciclosporin therapy and potential latent infection of an in-contact cat

Case summary: An 8-year-old domestic shorthair cat receiving long-term ciclosporin treatment was evaluated for a history of weight loss and hyporexia. The main clinical finding was a cluster of enlarged mesenteric lymph nodes. Cytological examination of fine-needle aspirates showed granulomatous inflammation with abundant acid-fast bacilli. A diagnosis of Mycobacterium avium complex (MAC) infection was confirmed by PCR. The cat’s clinical condition deteriorated rapidly despite appropriate antibiotic treatment and it was euthanased 2 weeks after initial presentation due to development of severe paraparesis and ataxia. Post-mortem examination revealed granulomatous inflammation affecting multiple lymph nodes and other organs with intrahistiocytic acid-fast bacilli consistent with mycobacteria when stained using Ziehl–Neelsen stain. Another cat in the same household was screened for infection using the interferon gamma release assay (IGRA), with the result being consistent with infection by non-tuberculous mycobacteria (NTM), which includes MAC; however, it had no grossly detectable disease. Relevance and novel information: This case report is an unusual presentation of disseminated MAC infection in a cat, which remains a rare diagnosis. Clinicians should be aware of unusual and rare presentations of this infection. The clinical findings, progression of disease and histopathology results add to the current clinical database for feline disseminated MAC infections. Another cat in the same household tested positive for NTM by IGRA without any gross disease. This was suggestive of latent MAC infection which, to our knowledge, has not been previously reported in an in-contact cat

An observational investigation of the faecal microbiota and metabonome of gastrostomy fed children, on blended and formula diets

Gastrostomy fed children traditionally have a Formulae diet (FD), which fulfills nutritional requirements; however, many families are adopting Blended diets (BD), which are what the whole family would eat. We undertook an observational investigation of the colonic microbiota and metabonome in a small group of gastrostomy fed children, who were either on an FD or BD, and compared, where possible to their siblings (17 FD, 28 BD, 19 HS). There was no increase in complications in tube blockage or infection rates, but a significant improvement in the prevalence of bowel problems, a reduction in medication and an increase in quality of life. Metataxonomic analysis showed that the FD group was significantly different to the Sibling group, and that families did not cluster together. Whole sample metabonomics showed no differences between groups; however, univariate analysis of biologically important metabolites did differ. Changing to a BD resulted in no increase in complications or risks, but improved the overall quality of life for the children and families