Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultraperformance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats.Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0±10.4%) andheart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influencedbymicrobial activitiesormodulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.

Utilisation by ruminants of nitrogen compounds in silage-based diets

This paper considers the various complex changes that occur to nitrogen (N) containing compounds in forages through the processes of ensiling, rumen degradation and microbial synthesis, post-ruminal digestion and absorption and synthesis into milk protein. Particular emphasis is placed on reviewing recent data on the efficiency of utilisation of N-containing compounds in silages by rumen microbes, since low efficiency here is believed to be a major cause of large N losses to the environment on some silage-based diets. Data are reviewed which show that although rumen degradation of N compounds in silage is rapid and extensive, up to 10% of the soluble N can escape the rumen by being associated with the liquid phase. There is now firm evidence that the composition of the amino acids (AAs) absorbed is heavily dependent on the process of ensiling and that witting or use of certain silage additives conserve the initial amino acid profile of the forage. This provides an opportunity to manipulate the amino acid supply to better match demand thus potentially enhancing utilisation. This review confirms that utilisation of the N fractions in grass and legume silages in particular, is poor and the efficiency of microbial protein synthesis (EMPS) is consistently higher on maize silage-based diets. It is concluded that the way in which grass and legume silages in particular are produced and used in the future needs a radical rethink. New research needs to be aimed at enhancing the utilisation of N in the rumen through a better understanding of N/carbohydrate relationships and the ability of forages to supply degraded carbohydrate. Also more emphasis is needed on understanding of the potentially different role of the different N fractions that exist in silages. (C) 2004 Elsevier B.V. All rights reserved.

A comparative evaluation of functions for partitioning nitrogen and amino acid intake between maintenance and growth in broilers

The results from three types of study with broilers, namely nitrogen (N) balance, bioassays and growth experiments, provided the data used herein. Sets of data on N balance and protein accretion (bioassay studies) were used to assess the ability of the monomolecular equation to describe the relationship between (i) N balance and amino acid (AA) intake and (ii) protein accretion and AA intake. The model estimated the levels of isoleucine, lysine, valine, threonine, methionine, total sulphur AAs and tryptophan resulting in zero balance to be 58, 59, 80, 96, 23, 85 and 32 mg/kg live weight (LW)/day, respectively. These estimates show good agreement with those obtained in previous studies. For the growth experiments, four models, specifically re-parameterized for analysing energy balance data, were evaluated for their ability to determine crude protein (CP) intake at maintenance and efficiency of utilization of CP intake for producing gain. They were: a straight line, two equations representing diminishing returns behaviour (monomolecular and rectangular hyperbola) and one equation describing smooth sigmoidal behaviour with a fixed point of inflexion (Gompertz). The estimates of CP requirement for maintenance and efficiency of utilization of CP intake for producing gain varied from 5.4 to 5.9 g/kg LW/day and 0.60 to 0.76, respectively, depending on the models.

Design of an active arm support for assisting arm movements

In this paper we have explored areas of application for health care manipulators and possible user groups. We have shown the steps in the design approach to the conceptual mechanism from the AAS. The future work will be measurement from properties of the muscle with the elbow parameterization test-bed to get a database to design one part of the control area from the AAS. More work on the mechanical design is required before a functional prototype can be built.

Gut microbiota modulate the metabolism of brown adipose tissue in mice

A two by two experimental study has been designed to determine the effect of gut microbiota on energy metabolism in mouse models. The metabolic phenotype of germ-free (GF, n = 20) and conventional (n = 20) mice was characterized using a NMR spectroscopy-based metabolic profiling approach, with a focus on sexual dimorphism (20 males, 20 females) and energy metabolism in urine, plasma, liver, and brown adipose tissue (BAT). Physiological data of age-matched GF and conventional mice showed that male animals had a higher weight than females in both groups. In addition, conventional males had a significantly higher total body fat content (TBFC) compared to conventional females, whereas this sexual dimorphism disappeared in GF animals (i.e., male GF mice had a TBFC similar to those of conventional and GF females). Profiling of BAT hydrophilic extracts revealed that sexual dimorphism in normal mice was absent in GF animals, which also displayed lower BAT lactate levels and higher levels of (D)-3-hydroxybutyrate in liver, plasma, and BAT, together with lower circulating levels of VLDL. These data indicate that the gut microbiota modulate the lipid metabolism in BAT, as the absence of gut microbiota stimulated both hepatic and BAT lipolysis while inhibiting lipogenesis. We also demonstrated that (1)H NMR metabolic profiles of BAT were excellent predictors of BW and TBFC, indicating the potential of BAT to fight against obesity.

Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n=5) and its germ-free (GF) equivalent (n=5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myo-inositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations.

The Prophetic Sound: a day and night of noise cabaret(symposium of talks and live performances)

'The Prophetic Sound: a day and night of noise cabaret' is the first event hosted by Agency of Noise. This all day event brought together artists and academics whose subject of focus is noise (in creative practice). Artists from across the UK were invited to consider a future post-digital era in which everything with a microchip has malfunctioned, as a thought exercise and starting point for response through sound. In response to Jacques Attali’s claim that music is prophecy, The Prophetic Sound asks us to consider if noise can communicate in an unbridled, unfiltered, way that is somehow not culturally coded -before it becomes sound that is recognised, refined, manipulated and exploited for musical or other cultured purpose. Featuring students from Reading, Brighton, LCC and Goldsmiths alongside more established artists and academics from across the UK, this event brings into focus locations where pattern, timbre, pitch, organisation and sequencing of sounds become distinguishable from noise and asks us to consider, through diversion within such locations, new origins for future communication systems. The Prophetic Sound included talks, films, presentations and performances from: Ryo Ikeshiro / Inigo Wilkins / Neal Spowage / Dane Sutherland / Poulomi Desai / Benedict Drew / AAS / Polly Fibre / Steven Dickie As part of The Prophetic Sound, POLLYFIBRE (Ellison, C.) performed LIVE RECORDING with Amplified Scissors. This industrial activity by POLLYFIBRE short-circuits the complicated chain that is music production. The distinctive roles of consumer, producer, composer, and performer collapse in a series of live ‘cuts’ where vinyl discs are produced with amplified scissors. Production happens through action and action becomes production. A limited edition of 9 flexi discs were produced and available for special collectors at the event.

Methane emissions from cattle: estimates from short-term measurements using a Green Feed system compared with measurements obtained using respiration chambers or sulphur hexafluoride tracer

The Green Feed (GF) system (C-Lock Inc., Rapid City, USA) is used to estimate total daily methane emissions of individual cattle using short-term measurements obtained over several days. Our objective was to compare measurements of methane emission by growing cattle obtained using the GF system with measurements using respiration chambers (RC)or sulphur hexafluoride tracer (SF6). It was hypothesised that estimates of methane emission for individual animals and treatments would be similar for GF compared to RC or SF6 techniques. In experiment 1, maize or grass silage-based diets were fed to four growing Holstein heifers, whilst for experiment 2, four different heifers were fed four haylage treatments. Both experiments were a 4 × 4 Latin square design with 33 day periods. Green Feed measurements of methane emission were obtained over 7 days (days 22–28) and com-pared to subsequent RC measurements over 4 days (days 29–33). For experiment 3, 12growing heifers rotationally grazed three swards for 26 days, with simultaneous GF and SF6 measurements over two 4 day measurement periods (days 15–19 and days 22–26).Overall methane emissions (g/day and g/kg dry matter intake [DMI]) measured using GF in experiments 1 (198 and 26.6, respectively) and 2 (208 and 27.8, respectively) were similar to averages obtained using RC (218 and 28.3, respectively for experiment 1; and 209 and 27.7, respectively, for experiment 2); but there was poor concordance between the two methods (0.1043 for experiments 1 and 2 combined). Overall, methane emissions measured using SF6 were higher (P<0.001) than GF during grazing (186 vs. 164 g/day), but there was significant (P<0.01) concordance between the two methods (0.6017). There were fewer methane measurements by GF under grazing conditions in experiment 3 (1.60/day) com-pared to indoor measurements in experiments 1 (2.11/day) and 2 (2.34/day). Significant treatment effects on methane emission measured using RC and SF6 were not evident for GF measurements, and the ranking for treatments and individual animals differed using the GF system. We conclude that under our conditions of use the GF system was unable to detectsignificant treatment and individual animal differences in methane emissions that were identified using both RC and SF6techniques, in part due to limited numbers and timing ofmeasurements obtained. Our data suggest that successful use of the GF system is reliant on the number and timing of measurements obtained relative to diurnal patterns of methane emission.

Factors that influence the detection of psychological problems in adolescents attending general practices

Background Epidemiological studies indicate that the prevalence of psychological problems in patients attending primary care services may be as high as 25%. Aim To identify factors that influence the detection of psychological difficulties in adolescent patients receiving primary care in the UK. Design of study A prospective study of 13-16 year olds consecutively attending general practices. Setting General practices, Norfolk, UK. Method Information was obtained from adolescents and parents using the validated Strengths and Difficulties Questionnaire (SDQ) and from GF`s using the consultation assessment form. Results Ninety-eight adolescents were recruited by 13 GPs in Norfolk (mean age = 14.4 years, SD = 1.08; 38 males, 60 females). The study identified psychological difficulties in almost one-third of adolescents (31/98, 31.6%). Three factors significant to the detection of psychological disorders in adolescents were identified: adolescents' perceptions of difficulties according to the self-report SDQ, the severity of their problems as indicated by the self-report SDQ, and whether psychological issues were discussed in the consultation. GPs did not always explore psychological problems with adolescents, even if GPs perceived these to be present. Nineteen of 31 adolescents with psychological difficulties were identified by GPs (sensitivity = 61.2%, specificity = 85.1%). A management plan or follow-up was made for only seven of 19 adolescents identified, suggesting that ongoing psychological difficulties in many patients are not being addressed. Conclusions GPs are in a good position to identify psychological issues in adolescents, but GPs and adolescents seem reluctant to explore these openly. Open discussion of psychological issues in GP consultations was found to be the most important factor in determining whether psychological difficulties in adolescents are detected by GPs.

Myth-science-colloquium

Group exhibition curated by Plastique Fantastique. Contributors include Plastique Fantastique, Tai Shani, Benedict Drew, Oreet Ashery, Tom Clarke, Mark Jackson, and AAS.