39 results found
Biggs MB, Medlock GL, Moutinho TJ, et al., Systems-level metabolism of the Altered Schaedler Flora, a complete gut microbiota, ISME Journal, ISSN: 1751-7362
The Altered Schaedler Flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition. We developed a chemically-defined medium that supported growth of seven of the eight ASF members. To elucidate the metabolic capabilities of these ASF species—including potential for interactions such as cross feeding—we performed a spent media screen and analyzed the results through dynamic growth measurements and non-targeted metabolic profiling. We found that cross-feeding is relatively rare (32 of 3 570 possible cases), but is enriched between Clostridium ASF356 and Parabacteroides ASF519. We identified many cases of emergent metabolism (856 of 3 570 possible cases). These data will inform efforts to understand ASF dynamics and spatial distribution in vivo, to design pre- and probiotics that modulate relative abundances of ASF members, and will be essential for validating computational models of ASF metabolism. Well-characterized, experimentally tractable microbial communities enable research that can translate into more effective microbiome-targeted therapies to improve human health.
Bolick DT, Mayneris-Perxachs J, Medlock GL, et al., Increased urinary trimethylamine N-oxide (TMAO) following Cryptosporidium infection and protein malnutrition independent of microbiome effects, Journal of Infectious Diseases, ISSN: 1537-6613
Mayneris-Perxachs J, Bolick DT, Leng J, et al., Protein and zinc deficient diets modulate the murine microbiome and metabolic phenotype, American Journal of Clinical Nutrition, ISSN: 1938-3207
Background: Environmental enteropathy, linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is first understanding the effects of nutritional deficiencies on the mammalian system, including the effect on the gut microbiota.Objective: We dissect the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut microbiota changes that occur in weaned mouse models of zinc or protein deficiency as compared to well-nourished controls. Design: Using a 1H NMR spectroscopy-based metabolic profiling approach with matching 16S microbiota analyses, the metabolic consequences and specific effects on the fecal microbiota of protein and zinc deficiency were probed independently in a murine model.Results: We find considerable shifts within the intestinal microbiota 14-24d post-weaning in mice maintained on a normal diet (including increases in Proteobacteria and striking decreases in Bacterioidetes). While the zinc deficient microbiota were comparable to the age-matched well-nourished profile, the protein-restricted microbiota remained closer in composition to the weaned enterotype with retention of Bacteroidetes. Striking increases in Verrucomicrobia (predominantly Akkermansia muciniphila) were observed in both well-nourished and protein-deficient mice 14d post-weaning. We find that protein malnutrition impairs growth and has major metabolic consequences (much more than zinc deficiency) that include altered energy, polyamine and purine/pyrimidine metabolism. Consistent with major changes in the gut microbiota, reductions in microbial proteolysis and increases in microbial dietary choline processing were observed.
Rowland I, Gibson G, Heinken A, et al., Gut microbiota functions: metabolism of nutrients and other food components, European Journal of Nutrition, ISSN: 1436-6207
Bolick DT, Mayneris-Perxachs J, Medlock GL, et al., 2017, Increased urinary trimethylamine N-oxide (TMAO) following Cryptosporidium infection and protein malnutrition independent of microbiome effects, The Journal of Infectious Diseases, ISSN: 0022-1899
Grimaldi R, Cela D, Swann JR, et al., 2017, In vitro fermentation of B-GOS: impact on faecal bacterial populations and metabolic activity in autistic and non-autistic children, FEMS Microbiology Ecology, Vol: 93, Pages: fiw233-fiw233
Li JV, Swann J, Marchesi JR, 2017, Biology of the Microbiome 2: Metabolic Role, Gastroenterology Clinics of North America, Vol: 46, Pages: 37-47, ISSN: 0889-8553
© 2016 Elsevier Inc.The human microbiome is a new frontier in biology and one that is helping to define what it is to be human. Recently, we have begun to understand that the “communication” between the host and its microbiome is via a metabolic superhighway. By interrogating and understanding the molecules involved we may start to know who the main players are, and how we can modulate them and the mechanisms of health and disease.
Massot-Cladera M, Mayneris-Perxachs J, Costabile A, et al., 2017, Association between urinary metabolic profile and the intestinal effects of cocoa in rats, British Journal of Nutrition, Vol: 117, Pages: 623-634, ISSN: 0007-1145
Swann JR, Garcia-Perez I, Braniste V, et al., 2017, Application of (1)H NMR spectroscopy to the metabolic phenotyping of rodent brain extracts: A metabonomic study of gut microbial influence on host brain metabolism., J Pharm Biomed Anal, Vol: 143, Pages: 141-146
(1)H NMR Spectroscopy has been applied to determine the neurochemical profiles of brain extracts from the frontal cortex and hippocampal regions of germ free and normal mice and rats. The results revealed a number of differences between germ free (GF) and conventional (CV) rats or specific pathogen-free (SPF) mice with microbiome-associated metabolic variation found to be both species- and region-dependent. In the mouse, the GF frontal cortex contained lower amounts of creatine, N-acetyl-aspartate (NAA), glycerophosphocholine and lactate, but greater amounts of choline compared to that of specific pathogen free (SPF) mice. In the hippocampus, the GF mice had greater creatine, NAA, lactate and taurine content compared to those of the SPF animals, but lower relative quantities of succinate and an unidentified lipid-related component. The GF rat frontal cortex contained higher relative quantities of lactate, creatine and NAA compared to the CV animals whilst the GF hippocampus was characterized by higher taurine and phosphocholine concentrations and lower quantities of NAA, N-acetylaspartylglutamate and choline compared to the CV animals. Of note is that, in both rat and mouse brain extracts, concentrations of hippocampal taurine were found to be greater in the absence of an established microbiome. The results provide further evidence that brain biochemistry can be influenced by gut microbial status, specifically metabolites involved in energy metabolism demonstrating biochemical dialogue between the microbiome and brain.
Bartelt LA, Swann JR, Guerrant RL, 2016, Decoding Hidden Messages: Can Fecal Host Transcriptomics Open Pathways to Understanding Environmental Enteropathy?, Cellular and Molecular Gastroenterology and Hepatology, Vol: 2, Pages: 114-115, ISSN: 2352-345X
Bottin JH, Swann JR, Cropp E, et al., 2016, Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial, BRITISH JOURNAL OF NUTRITION, Vol: 116, Pages: 360-374, ISSN: 0007-1145
Darzi J, Frost GS, Swann JR, et al., 2016, L-rhamnose as a source of colonic propionate inhibits insulin secretion but does not influence measures of appetite or food intake, APPETITE, Vol: 98, Pages: 142-149, ISSN: 0195-6663
Farshim P, Walton G, Chakrabarti B, et al., 2016, Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322
Grimaldi R, Swann JR, Vulevic J, et al., 2016, Fermentation properties and potential prebiotic activity of Bimuno® galacto-oligosaccharide (65 % galacto-oligosaccharide content) on in vitro gut microbiota parameters, British Journal of Nutrition, Vol: 116, Pages: 480-486, ISSN: 0007-1145
Guerrant RL, Leite AM, Pinkerton R, et al., 2016, Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil, PLOS ONE, Vol: 11, Pages: e0158772-e0158772
Mayneris-Perxachs J, Lima AAM, Guerrant RL, et al., 2016, Urinary N-methylnicotinamide and β-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children, Scientific Reports, Vol: 6
Omairi S, Matsakas A, Degens H, et al., 2016, Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres, eLife, Vol: 5, ISSN: 2050-084X
A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn-/-/ErrγTg/+) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn-/-/ErrγTg/+ mouse showed satellite cell deficit which unexpectedly did not affect muscle regeneration. These observations 1) challenge the concept of a constraint between fibre size and oxidative capacity and 2) indicate the important role of the microcirculation in the regenerative capacity of a muscle even when satellite cell numbers are reduced.
Collins-Hooper H, Sartori R, Giallourou N, et al., 2015, Correction: Symmorphosis through Dietary Regulation: A Combinatorial Role for Proteolysis, Autophagy and Protein Synthesis in Normalising Muscle Metabolism and Function of Hypertrophic Mice after Acute Starvation., PLoS One, Vol: 10
Escalona EE, Leng J, Dona AC, et al., 2015, Dominant components of the Thoroughbred metabolome characterised by H-1-nuclear magnetic resonance spectroscopy: A metabolite atlas of common biofluids, EQUINE VETERINARY JOURNAL, Vol: 47, Pages: 721-730, ISSN: 0425-1644
Matsakas A, Prosdocimo DA, Mitchell R, et al., 2015, Investigating mechanisms underpinning the detrimental impact of a high-fat diet in the developing and adult hypermuscular myostatin null mouse., Skelet Muscle, Vol: 5
BACKGROUND: Obese adults are prone to develop metabolic and cardiovascular diseases. Furthermore, over-weight expectant mothers give birth to large babies who also have increased likelihood of developing metabolic and cardiovascular diseases. Fundamental advancements to better understand the pathophysiology of obesity are critical in the development of anti-obesity therapies not only for this but also future generations. Skeletal muscle plays a major role in fat metabolism and much work has focused in promoting this activity in order to control the development of obesity. Research has evaluated myostatin inhibition as a strategy to prevent the development of obesity and concluded in some cases that it offers a protective mechanism against a high-fat diet. METHODS: Pregnant as well as virgin myostatin null mice and age matched wild type animals were raised on a high fat diet for up to 10 weeks. The effect of the diet was tested on skeletal muscle, liver and fat. Quantitate PCR, Western blotting, immunohistochemistry, in-vivo and ex-vivo muscle characterisation, metabonomic and lipidomic measurements were from the four major cohorts. RESULTS: We hypothesised that myostatin inhibition should protect not only the mother but also its developing foetus from the detrimental effects of a high-fat diet. Unexpectedly, we found muscle development was attenuated in the foetus of myostatin null mice raised on a high-fat diet. We therefore re-examined the effect of the high-fat diet on adults and found myostatin null mice were more susceptible to diet-induced obesity through a mechanism involving impairment of inter-organ fat utilization. CONCLUSIONS: Loss of myostatin alters fatty acid uptake and oxidation in skeletal muscle and liver. We show that abnormally high metabolic activity of fat in myostatin null mice is decreased by a high-fat diet resulting in excessive adipose deposition and lipotoxicity. Collectively, our genetic loss-of-function studies offer an explanation of th
Bodinham CL, Smith L, Thomas EL, et al., 2014, Efficacy of increased resistant starch consumption in human type 2 diabetes, ENDOCRINE CONNECTIONS, Vol: 3, Pages: 75-84
Daud NM, Ismail NA, Thomas EL, et al., 2014, The Impact of Oligofructose on Stimulation of Gut Hormones, Appetite Regulation and Adiposity, OBESITY, Vol: 22, Pages: 1430-1438, ISSN: 1930-7381
Frost G, Sleeth ML, Sahuri-Arisoylu M, et al., 2014, The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723
Frost GS, Walton GE, Swann JR, et al., 2014, Impacts of Plant-Based Foods in Ancestral Hominin Diets on the Metabolism and Function of Gut Microbiota In Vitro, MBIO, Vol: 5, ISSN: 2150-7511
Gan XT, Ettinger G, Huang CX, et al., 2014, Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat, Circulation: Heart Failure, Vol: 7, Pages: 491-499, ISSN: 1941-3289
Kok MGM, Swann JR, Wilson ID, et al., 2014, Hydrophilic interaction chromatography–mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats, Journal of Pharmaceutical and Biomedical Analysis, Vol: 92, Pages: 98-104, ISSN: 0731-7085
Lees H, Swann J, Poucher SM, et al., 2014, Age and Microenvironment Outweigh Genetic Influence on the Zucker Rat Microbiome, PLOS ONE, Vol: 9, ISSN: 1932-6203
Reid G, Nduti N, Sybesma W, et al., 2014, Harnessing microbiome and probiotic research in sub-Saharan Africa: recommendations from an African workshop, Microbiome, Vol: 2, Pages: 12-12, ISSN: 2049-2618
Swann JR, Claus SP, 2014, Nutrimetabonomics: nutritional applications of metabolic profiling, Science Progress, Vol: 97, Pages: 41-47, ISSN: 0036-8504
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