Variation in antibiotic-induced microbial recolonization impacts on the host metabolic phenotypes of rats

The interaction between the gut microbiota and their mammalian host is known to have far-reaching consequences with respect to metabolism and health. We investigated the effects of eight days of oral antibiotic exposure (penicillin and streptomycin sulfate) on gut microbial composition and host metabolic phenotype in male Han-Wistar rats (n = 6) compared to matched controls. Early recolonization was assessed in a third group exposed to antibiotics for four days followed by four days recovery (n = 6). Fluorescence in situ hybridization analysis of the intestinal contents collected at eight days showed a significant reduction in all bacterial groups measured (control, 1010.7 cells/g feces; antibiotic-treated, 108.4). Bacterial suppression reduced the excretion of mammalian-microbial urinary cometabolites including hippurate, phenylpropionic acid, phenylacetylglycine and indoxyl-sulfate whereas taurine, glycine, citrate, 2-oxoglutarate, and fumarate excretion was elevated. While total bacterial counts remained notably lower in the recolonized animals (109.1 cells/g faeces) compared to the controls, two cage-dependent subgroups emerged with Lactobacillus/Enterococcus probe counts dominant in one subgroup. This dichotomous profile manifested in the metabolic phenotypes with subgroup differences in tricarboxylic acid cycle metabolites and indoxyl-sulfate excretion. Fecal short chain fatty acids were diminished in all treated animals. Antibiotic treatment induced a profound effect on the microbiome structure, which was reflected in the metabotype. Moreover, the recolonization process was sensitive to the microenvironment, which may impact on understanding downstream consequences of antibiotic consumption in human populations.

Formation of isopolyoxometallate(VI) anions in the reaction between M(CO)6 (M = W, Mo) and acetic acid: X-ray crystal structure of [W3(μ3-O)2(μ2η2-O2CCH3)6(H2O)3]2[W10O32·solvent

W(CO)6 reacts with a mixture of acetic acid/acetic anhydride to give [W3 (μ3-O)2(μ2η2-O2CCH3)6(H2O)3](CH3CO2)2 (1), which was converted by HClO4 to [W3 (μ3-O)2(μ2η2-O2CCH3)6(H2O)3](ClO4)2 (2). Addition of CH3CO2Na to the above reaction mixture, and prolonged exposure of the solution to air, results in the formation of the WIV/WVI complex salt [W3(μ3-O)2(μ2η2-O2CCH3)6(H2O)3]2[W10O32]·solvent (3). Complex 3 was also prepared by reacting 1 with Na2WO4·2H2O in acetic acid, and it has been characterized by X-ray crystallography. Addition of [CH3(CH2)3]4N(ClO4) to the reaction filtrate remaining after the preparation of [Mo2(μ-O2CCH3)4][from Mo(CO)6, CH3CO2H and (CH3CO)2O], followed by exposure to air, gives ([CH3(CH2)3]4N)2[Mo6O19] (4).

Analysis of time-related metabolic fluctuations induced by ethionine in the rat

The time-course of metabolic events following response to a model hepatotoxin ethionine (800 mg/kg) was investigated over a 7 day period in rats using high-resolution (1)H NMR spectroscopic analysis of urine and multivariate statistics. Complementary information was obtained by multivariate analysis of (1)H MAS NMR spectra of intact liver and by conventional histopathology and clinical chemistry of blood plasma. (1)H MAS NMR spectra of liver showed toxin-induced lipidosis 24 h postdose consistent with the steatosis observed by histopathology, while hypertaurinuria was suggestive of liver injury. Early biochemical changes in urine included elevation of guanidinoacetate, suggesting impaired methylation reactions. Urinary increases in 5-oxoproline and glycine suggested disruption of the gamma-glutamyl cycle. Signs of ATP depletion together with impairment of the energy metabolism were given from the decreased levels in tricarboxylic acid cycle intermediates, the appearance of ketone bodies in urine, the depletion of hepatic glucose and glycogen, and also hypoglycemia. The observed increase in nicotinuric acid in urine could be an indication of an increase in NAD catabolism, a possible consequence of ATP depletion. Effects on the gut microbiota were suggested by the observed urinary reductions in the microbial metabolites 3-/4-hydroxyphenyl propionic acid, dimethylamine, and tryptamine. At later stages of toxicity, there was evidence of kidney damage, as indicated by the tubular damage observed by histopathology, supported by increased urinary excretion of lactic acid, amino acids, and glucose. These studies have given new insights into mechanisms of ethionine-induced toxicity and show the value of multisystem level data integration in the understanding of experimental models of toxicity or disease.

Immune factors and fatty acid composition in human milk from river/lake, coastal and inland regions of China

Breast milk fatty acid composition may be affected by maternal diet during gestation and lactation. The influence of dietary and breast milk fatty acids on breast milk immune factors is poorly defined. We determined the fatty acid composition and immune factor concentrations of breast milk from women residing in river & lake, coastal, and inland regions of China, which differ in their consumption of lean fish and oily fish. Breast milk samples were collected on days 3 to 5 (colostrum), 14 and 28 post-partum and analysed for soluble CD14 (sCD14), transforming growth factor (TGF)-β1, TGF-β2, secretory immunoglobulin A (sIgA) and fatty acids. The fatty acid composition of breast milk differed between regions and with time post-partum. The concentrations of all four immune factors in breast milk decreased over time, with sCD14, sIgA and TGF-β1 being highest in colostrum in the river & lake region. Breast milk DHA and arachidonic acid (AA) were positively associated, and γ-linolenic acid and EPA negatively associated, with the concentrations of each of the four immune factors. In conclusion, breast milk fatty acids and immune factors differ between regions in China characterised by different patterns of fish consumption and change during the course of lactation. A higher breast milk DHA and AA concentration is associated with higher concentrations of immune factors in breast milk, suggesting a role for these fatty acids in promoting gastrointestinal and immune maturation of the infant.

Premature impairment of methylation pathway and cardiac metabolic dysfunction in fa/fa obese Zucker rats

Increasing evidence suggests that obesity is a chronic inflammatory disease, in which adipose tissue is involved in a network of endocrine signals to modulate energy homeostasis. These oxidative-inflammatory pathways, which are associated with cardiovascular complications, are also observed during the aging process. In this study, we investigated the interaction between aging and the development of obesity in a hyperphagic rat model. Metabolic profiles of the liver, white adipose tissue (WAT) and heart from young and adult Zucker lean (fa/+) and obese (fa/fa) rats were characterized using a (1)H NMR-based metabonomics approach. We observed premature metabolic modifications in all studied organs in obese animals, some of which were comparable to those observed in adult lean animals. In the cardiac tissue, young obese rats displayed lower lactate and scyllo-inositol levels associated with higher creatine, choline and phosphocholine levels, indicating an early modulation of energy and membrane metabolism. An early alteration of the hepatic methylation and transsulfuration pathways in both groups of obese rats indicated that these pathways were affected before diabetic onset. These findings therefore support the hypothesis that obesity parallels some metabolic perturbations observed in the aging process and provides new insights into the metabolic modifications occurring in pre-diabetic state.

Sulphate and sulphurous acid alter the relative susceptibility of wheat to Phaeosphaeria nodorum and Mycosphaerella graminicola

The relative abundances of DNA of Mycosphaerella graminicola and Phaeosphaeria nodorum in archived wheat samples are closely correlated with UK anthropogenic emissions of oxidized sulphur over the last 160 years. To test whether this could be a causal relationship, possible modes of action of sulphur on the two fungi were examined. Mycelial growth of the two fungi in solutions of sulphurous acid was similar. Sulphurous acid at pH 4 reduced percentage germination of P. nodorum conidia more strongly than M. graminicola conidia. In spray inoculations of wheat cv. Squarehead’s Master, Cappelle Desprez and Riband with water or sulphurous acid (pH 4), the ratio of leaves infected by P. nodorum to leaves infected by M. graminicola was increased by factors of 2.5, 2.1 and 0.6, respectively at pH 4. The same three cultivars of wheat were grown in sand and vermiculite and fertilized with nutrient solution containing 2.5 or 0.5 mM sulphate. Both pathogens infected less frequently at 2.5 mM sulphate, by a factor of about 2. The severity of infection by M. graminicola was reduced on all three cultivars by a factor of about 4-5 at 2.5mM sulphate, but severity of P. nodorum was reduced only by a factor of about 2. Both elevated free sulphate concentrations in soil and sulphite in rainwater could therefore increase the prevalence of P. nodorum relative to M. graminicola, which is consistent with the historical changes in abundance

Global vegetation and terrestrial carbon cycle changes after the last ice age

•In current models, the ecophysiological effects of CO2 create both woody thickening and terrestrial carbon uptake, as observed now, and forest cover and terrestrial carbon storage increases that took place after the last glacial maximum (LGM). Here, we aimed to assess the realism of modelled vegetation and carbon storage changes between LGM and the pre-industrial Holocene (PIH). •We applied Land Processes and eXchanges (LPX), a dynamic global vegetation model (DGVM), with lowered CO2 and LGM climate anomalies from the Palaeoclimate Modelling Intercomparison Project (PMIP II), and compared the model results with palaeodata. •Modelled global gross primary production was reduced by 27–36% and carbon storage by 550–694 Pg C compared with PIH. Comparable reductions have been estimated from stable isotopes. The modelled areal reduction of forests is broadly consistent with pollen records. Despite reduced productivity and biomass, tropical forests accounted for a greater proportion of modelled land carbon storage at LGM (28–32%) than at PIH (25%). •The agreement between palaeodata and model results for LGM is consistent with the hypothesis that the ecophysiological effects of CO2 influence tree–grass competition and vegetation productivity, and suggests that these effects are also at work today.

Response to zinc deficiency of two rice lines with contrasting tolerance is determined by root growth maintenance and organic acid exudation rates, and not by zinc-transporter activity

Zinc (Zn)-deficient soils constrain rice (Oryza sativa) production and cause Zn malnutrition. The identification of Zn-deficiency-tolerant rice lines indicates that breeding might overcome these constraints. Here, we seek to identify processes underlying Zn-deficiency tolerance in rice at the physiological and transcriptional levels. A Zn-deficiency-tolerant line RIL46 acquires Zn more efficiently and produces more biomass than its nontolerant maternal line (IR74) at low Zn(ext) under field conditions. We tested if this was the result of increased expression of Zn(2+) transporters; increased root exudation of deoxymugineic acid (DMA) or low-molecular-weight organic acids (LMWOAs); and/or increased root production. Experiments were performed in field and controlled environment conditions. There was little genotypic variation in transcript abundance of Zn-responsive root Zn(2+)-transporters between the RIL46 and IR74. However, root exudation of DMA and LMWOA was greater in RIL46, coinciding with increased root expression of putative ligand-efflux genes. Adventitious root production was maintained in RIL46 at low Zn(ext), correlating with altered expression of root-specific auxin-responsive genes. Zinc-deficiency tolerance in RIL46 is most likely the result of maintenance of root growth, increased efflux of Zn ligands, and increased uptake of Zn-ligand complexes at low Zn(ext); these traits are potential breeding targets.

Hollow capsules formed in a single stage via interfacial hydrogen-bonded complexation of methylcellulose with poly(acrylic acid) and tannic acid

Hollow capsules can be prepared in a single stage by the interfacial complexation of methylcellulose (MC) with poly(acrylic acid) (PAA) or tannic acid (TA) via hydrogen bonding in aqueous solutions. The formation of capsules is observed when viscous solution of methylcellulose is added drop-wise to diluted solutions of polyacids under acidic conditions. The optimal parameters such as polymer concentration and solution pH for the formation of these capsules were established in this work. It was found that tannic acid forms capsules in a broader range of concentrations and pHs compared to poly(acrylic acid). The TA/MC capsules exhibited better stability compared to PAA/MC in response to increase in pH: the dissolution of TA/MC capsules observed at pH > 9.5; whereas PAA/MC capsules dissolved at pH > 3.8. The interfacial complexation can be considered as a potential single stage alternative to the formation of capsules using multistage layer-by-layer deposition method.

The Madden-Julian Oscillation and the diurnal cycle over the Maritime Continent: scale interactions and modelling

The Maritime Continent archipelago, situated on the equator at 95-165E, has the strongest land-based precipitation on Earth. The latent heat release associated with the rainfall affects the atmospheric circulation throughout the tropics and into the extra-tropics. The greatest source of variability in precipitation is the diurnal cycle. The archipelago is within the convective region of the Madden-Julian Oscillation (MJO), which provides the greatest variability on intra-seasonal time scales: large-scale (∼10^7 km^2) active and suppressed convective envelopes propagate slowly (∼5 m s^-1) eastwards between the Indian and Pacific Oceans. High-resolution satellite data show that a strong diurnal cycle is triggered to the east of the advancing MJO envelope, leading the active MJO by one-eighth of an MJO cycle (∼6 days). Where the diurnal cycle is strong its modulation accounts for 81% of the variability in MJO precipitation. Over land this determines the structure of the diagnosed MJO. This is consistent with the equatorial wave dynamics in existing theories of MJO propagation. The MJO also affects the speed of gravity waves propagating offshore from the Maritime Continent islands. This is largely consistent with changes in static stability during the MJO cycle. The MJO and its interaction with the diurnal cycle are investigated in HiGEM, a high-resolution coupled model. Unlike many models, HiGEM represents the MJO well with eastward-propagating variability on intra-seasonal time scales at the correct zonal wavenumber, although the inter-tropical convergence zone's precipitation peaks strongly at the wrong time, interrupting the MJO's spatial structure. However, the modelled diurnal cycle is too weak and its phase is too early over land. The modulation of the diurnal amplitude by the MJO is also too weak and accounts for only 51% of the variability in MJO precipitation. Implications for forecasting and possible causes of the model errors are discussed, and further modelling studies are proposed.

Ionospheric convection and the substorm cycle

During substorms, magnetic energy is stored and released by the geomagnetic tail in cycles of growth and expansion phases, respectively. Hence substorms are inherently non-steady phenomena. On the other hand, all numerical models (and most conceptual ones) of ionospheric convection produced to date have considered only steady-state situations. In this paper, we investigate the relationship of substorms to convection. In particular, it is shown that the steady-state convection pattern represents an average over several substorm cycles and does not apply on time scales shorter than the substorm cycle period of 1-2 hours. The flows driven by the growth and expansion phases of substorms are integral (indeed dominant) part of, as opposed to a transient addition to, the overall convection pattern.

In vitro colonic metabolism of coffee and chlorogenic acid results in selective changes in human faecal microbiota growth

Coffee is a relatively rich source of chlorogenic acids (CGA), which, like other polyphenols are postulated to exert preventative effects against cardiovascular disease and type-2 diabetes. As a considerable proportion of ingested CGA reaches the large intestine, CGA may be capable of exerting beneficial effects in the large gut. Here we utilise a stirred, anaerobic, pH controlled, batch culture fermentation model of the distal region of the colon in order to investigate the impact of coffee and CGA on the growth of the human faecal microbiota. Incubation of the coffee with the human faecal microbiota led to the rapid metabolism of CGA (4h) and the production of dihydrocaffeic acid and dihydroferulic acid, whilst caffeine remained un-metabolised. The coffee with the highest levels of CGA (p<0.05, relative to the other coffees) induced a significant increase in Bifidobacterium spp. relative to the control at 10 hours post exposure (p<0.05). Similarly, an equivalent quantity of CGA (80.8mg; matched with that in high CGA coffee) induced a significant increase in Bifidobacterium spp. (p<0.05). CGA alone also induced a significant increase in the Clostridium coccoides-Eubacterium rectale group (p<0.05). This selective metabolism and subsequent amplification of specific bacterial populations could be beneficial to host health.