Imperial College London


Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Research Associate







Sir Alexander Fleming BuildingSouth Kensington Campus





Publication Type

4 results found

Biggs MB, Medlock GL, Moutinho TJ, Lees HJ, Swann JR, Kolling GL, Papin JAet al., 2016, 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.

Journal article

Phetcharaburanin J, Lees H, Marchesi JR, Nicholson JK, Holmes E, Seyfried F, Li JVet al., 2016, Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metab-olism and Host-Microbial Interactions, Journal of Proteome Research, Vol: 15, Pages: 1897-1906, ISSN: 1535-3907

The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolicnetworks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is importantto further our understanding of the circulation of the microbial or host-microbial metabolites and their impact on hostmetabolism. 1H Nuclear Magnetic Resonance spectroscopy-based metabolic profiling was used to probe global metabolicdifferences 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 leanZucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid andglycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless ofphenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portalvein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observedin portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that theabsorption of propionate and acetate, choline and TMA are independent of the Zucker rat phenotypes. However, urinaryhost-microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activitiesin 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.

Journal article

Lees H, Swann J, Poucher SM, Nicholson JK, Holmes E, Wilson ID, Marchesi JRet al., 2014, Age and Microenvironment Outweigh Genetic Influence on the Zucker Rat Microbiome, PLOS One, Vol: 9, ISSN: 1932-6203

ArticleAuthorsMetricsCommentsRelated ContentAbstractIntroductionMethodsResultsDiscussionConclusionsSupporting InformationAuthor ContributionsReferencesReader Comments (0)Media Coverage (0)FiguresAbstractAnimal models are invaluable tools which allow us to investigate the microbiome-host dialogue. However, experimental design introduces biases in the data that we collect, also potentially leading to biased conclusions. With obesity at pandemic levels animal models of this disease have been developed; we investigated the role of experimental design on one such rodent model. We used 454 pyrosequencing to profile the faecal bacteria of obese (n = 6) and lean (homozygous n = 6; heterozygous n = 6) Zucker rats over a 10 week period, maintained in mixed-genotype cages, to further understand the relationships between the composition of the intestinal bacteria and age, obesity progression, genetic background and cage environment. Phylogenetic and taxon-based univariate and multivariate analyses (non-metric multidimensional scaling, principal component analysis) showed that age was the most significant source of variation in the composition of the faecal microbiota. Second to this, cage environment was found to clearly impact the composition of the faecal microbiota, with samples from animals from within the same cage showing high community structure concordance, but large differences seen between cages. Importantly, the genetically induced obese phenotype was not found to impact the faecal bacterial profiles. These findings demonstrate that the age and local environmental cage variables were driving the composition of the faecal bacteria and were more deterministically important than the host genotype. These findings have major implications for understanding the significance of functional metagenomic data in experimental studies and beg the question; what is being measured in animal experiments in which different strains are housed separately, nature or nurture?

Journal article

Lees HJ, Swann JR, Wilson ID, Nicholson JK, Holmes Eet al., 2013, Hippurate: The Natural History of a Mammalian-Microbial Cometabolite, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 1527-1546, ISSN: 1535-3893

Journal article

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