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

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

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

An assessment of case-fatality and infection-fatality rates of first and second COVID-19 waves in italy

Background and aim: The exact COVID-19 severity is still not well defined and it is hotly debated due to a few methodological issues such as the uncertainties about the spread of the SARS-CoV-2 infection. Methods: We investigated COVID-19 case-fatality rate and infection-fatality rate in 2020 in Italy, a country severely affected by the pandemic, basing our assessment on publicly available data, and calculating such measures during the first and second waves. Results: We found that province-specific crude case-fatality rate in the first wave (February-July 2020) had a median value of 12.0%. Data about infection-fatality rate was more difficult to compute, due to large underestimation of SARS-CoV-2 infection during the first wave when asymptomatic individuals were very rarely tested. However, when using reference population-based seroprev-alence data for anti-SARS-CoV-2 antibodies collected in May-July 2020, we computed an infection-fatality rate of 2.2%. During the second wave (Sep-Dec 2020), when SARS-CoV-2 testing was greatly increased and extended to many asymptomatic individuals, we could only compute a ‘hybrid’ case/infection-fatality rate with a value of 2.2%, similar to the infection-fatality rate of the first wave. Conclusions: Overall, this study al-lowed to assess the COVID-19 case-and infection-fatality rates in Italy before of variant spread and vaccine availability, confirming their high values compared with other airborne infections like influenza. Our findings for Italy were similar to those characterizing other Western European countries

The Bacteroidales produce an N-acylated derivative of glycine with both cholesterol-solubilising and hemolytic activity.

The contribution of the gut microbiota to the metabolism of cholesterol is not well understood. In this study, we identify 21 fosmid clones from a human gut microbiome metagenomic library that, when expressed in Escherichia coli, produce halos on LB agar supplemented with 0.01% (w/v) cholesterol (LBC agar). Analysis of 14 of these clones revealed that they all share a fragment of DNA with homology to the genome of Bacteroides vulgatus. The gene responsible for halo production on LBC agar, named choA, was identified as an N-acyltransferase known to produce an acylated glycine molecule called commendamide. In this study we show that commendamide is capable of producing a halo on LBC agar suggesting that this molecule is solubilizing the cholesterol micelles in LBC agar. We also show that commendamide is responsible for the previously described hemolytic activity associated with the choA orthologue in Bacteroides fragilis. A functional analysis of ChoA identified 2 amino acids that are important for commendamide biosynthesis and we present phylogenetic and functional data showing that orthologues of choA are found only in the order Bacteroidales. Therefore, the production of commendamide may be an adaptation to the environments colonized by the Bacteroidales, including the mammalian gut

Use of intravesical injections of platelet-rich plasma for the treatment of bladder pain syndrome: A comprehensive literature review

Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. Methods: A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: “platelet-rich plasma”, “interstitial cystitis”, “PRP”, “bladder pain syndrome”, and “painful bladder syndrome”. Results: After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. Conclusions: New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology

Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metab-olism and Host-Microbial Interactions

The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolic networks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is important to further our understanding of the circulation of the microbial or host–microbial metabolites and their impact on host metabolism. 1H nuclear magnetic resonance spectroscopy-based metabolic profiling was used to probe global metabolic differences in portal vein and peripheral blood plasma, urine and fecal water between obese (fa/fa, n = 12) and lean (fa/+, n = 12) Zucker rats. Urinary concentrations of host–microbial co-metabolites were found to be significantly higher in lean Zucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid and glycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless of phenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portal vein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observed in portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that the absorption of propionate, acetate, choline, and trimethylamine is independent of the Zucker rat phenotypes. However, urinary host–microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activities in lean and obese Zucker rats. This work advances our understanding of metabolic processes associated with obesity, particularly the metabolic functionality of the gut microbiota in the context of obesity