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The University of Aberdeen
Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
phone: +44 1224 438651
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The mammalian gut is colonized by a dense and complex microbial community that has a major influence on nutrition and health (Flint et al., 2012). The main energy sources for microbial growth in the large intestine of man and farm animals, and also in the rumen, are plant-derived fibre and polysaccharides. Our research employs molecular community analysis, anaerobic microbiology, metabolic profiling and genome data to identify the roles of particular bacteria in gut microbial communities, with particular emphasis on the degradation of insoluble substrates such as plant cell walls and resistant starch particles in the human large intestine (Duncan SH et al., 2016; Ze X et al., 2012). ‘Keystone’ species of the genus Ruminococcus isolated from humans have been shown recently to elaborate extracellular enzyme complexes that mediate substrate breakdown – cellulosomes (in the cellulolytic species R. champanellensis - Ben David Y et al., 2015) and amylosomes (in the specialist starch degrader R. bromii – Ze X et al., 2015). In contrast, such complexes are absent from the related human colonic species “R. bicirculans”, which is non-cellulolytic but can grow on soluble glucans and mannans (Wegmann U et al., 2013). Among the Lachnospiraceae, a second dominant family of Firmicutes bacteria found in the human intestine, comparative genomics revealed a variable distribution of polysaccharide utilization loci that can account for interspecies variation in the utilization of some commonly used prebiotics (Sheridan P et al., 2016; Scott et al., 2014). Human dietary intervention studies have allowed us to gain unique information on the dynamics of the gut community in response to changing between diets enriched in resistant starch and wheat bran, and on the impact of inter-individual variation. Changes in particular ‘diet responsive’ species (mainly Firmicutes) occurred within a few days of the diet switch and were reversible by a subsequent dietary shift (Walker AW et al., 2011; Salonen A et al., 2014). In vitro continuous culture systems, employed to examine competition for single polysaccharide substrates, have revealed that responses are often highly species-specific (Chung WCF et al., 2016). Human dietary intervention studies have allowed us to gain unique information on the dynamics of the gut community in response to changing between diets enriched in resistant starch and wheat bran, and on the impact of inter-individual variation. Changes in particular ‘diet responsive’ species (mainly Firmicutes) occurred within a few days of the diet switch and were reversible by a subsequent dietary shift (Walker AW et al., 2011; Salonen A et al., 2014). In vitro continuous culture systems, employed to examine competition for single polysaccharide substrates, have revealed that responses are often highly species-specific (Chung WCF et al., 2016). Metabolites that are produced or released by gut micro-organisms have an important influence on health and on host metabolism (Louis et al., 2014). Human colonic bacteria that degrade wheat bran were recently shown to release ferulic acid, which is then transformed by other members of the microbiota (Duncan SH et al., 2016). Short chain fatty acids, which are the major products of anaerobic metabolism, have multiple effects on the host as energy sources, signal molecules and regulators of gene expression. The phylogenetic distribution of pathways for butyrate and propionate formation by the human intestinal microbiota has been investigated by interrogating genomic data from cultured isolates and metagenomic data (Reichardt N et al., 2014). Recent work has highlighted the phylogeny and ecology of important butyrate-producing bacteria including Faecalibacterium prausnitzii (Lopez-Siles M et al., 2012, Khan T et al., 2012) and Roseburia spp. (Hatziioanou et al., 2013; Neville A et al., 2013) and identified a new lactate-utilizing species, Anaerostipes hadrus (Allen-Vercoe E et al., 2012). We have also collaborated with mathematicians in BioSS on the development of a theoretical model of the human intestinal microbiota that assumes 10 bacterial functional groups differing in substrate preferences, metabolic products and responses to gut pH. This model has proved successful in simulating the impact of a one-unit pH shift upon the complete human intestinal microbiota in continuous flow fermentor experiments (Kettle H et al., 2015).
Invited Lectures (2015-17)
Nature Café on the role of microbiota in health and disease. Invited speaker London, UK (October 2017)
University of Chicago. Invited speaker to initiate new Microbiome seminar programme (September 2017)
Gordon Research Conference on ‘Cellulases and related enzymes’. Invited speaker New Hampshire, USA (July 2017)
International Society for Anaerobic Microbiology (ISAM) meeting. Invited lecture, Prague (June 2017)
Invited speaker Seonn conference, Germany (June 2016).
10Th INRA-Rowett meeting on Gut Microbiology. Invited plenary speaker, Clermont Ferrand, France (June 2016)
Nutrigenomics conference. University of Camerino, Italy (September 2016)
Institut Biomerieux symposium. Invited speaker, Lac D’Annecy, France (April 2016)
Harvard Postgraduate Medical School. Keynote lecture (July 2015)
Harry Flint holds a personal Professorship at the University of Aberdeen. He obtained his BSc and PhD in Genetics from the University of Edinburgh and subsequently held appointments at the Universities of Nottingham, the West Indies and Edinburgh before joining the Rowett Institute in Aberdeen in 1985. Harry’s research focusses on the contribution of commensal and symbiotic micro-organisms inhabiting the mammalian gut to nutrition and health. His investigations combine molecular approaches with cultural microbiology, dietary interventions and modelling to uncover the roles of human colonic gut bacteria in fermentative metabolism and the degradation of dietary components, especially resistant starches and plant cell wall polysaccharides. Harry led successive Scottish Government-funded 5-year research programmes on Gut Health over the past 15 years and has also pursued research projects funded by the EU, charities (WCRF), UK Research Councils (BBSRC, MRC), commercial partners and NIH. He has served on the UK ACNFP (Advisory Committee for Novel Foods and Processes) and as a Scientific Governor of the British Nutrition Foundation.
Microbial ecology of the gut including community dynamics, competition and cross-feeding. Organization of microbial enzyme systems for the degradation and utilization of polysaccharides. Dominant groups of anaerobic gut bacteria responsible for the production and interconversion of organic acids (especially production of butyrate and utilization of lactate). Gene transfer between gut bacteria (antibiotic resistance genes).
Harry Flint’s research focuses on the impact of commensal and symbiotic micro-organisms in the mammalian gut on nutrition and health. He combines cultural microbiology with molecular approaches to uncover the roles of human colonic bacteria in fermentative metabolism and the degradation of dietary components. Genomic and functional analyses of bacteria isolated from the human and animal gut have revealed the role of enzyme complexes (cellulosome and amylosome) in the degradation of different types of fibre and resistant starch by gram-positive anaerobes. The impact of different types of fibre upon gut microbiota composition in vivo has been revealed through analysis of ribosomal amplicons in human volunteer studies that allow complete control over dietary intake. Microbial competition for particular fibres, and the influence of gut pH, are also analyzed using controlled in vitro conditions in continuous flow fermentor systems.Another important aim has been to understand the factors that determine metabolic outputs of the gut microbiota that have consequences for health. Progress has been made in identifying the phylogenetic groups responsible for key functions such as formation of the short chain fatty acids butyrate and propionate and the utilization of lactic acid in the human large intestine, and in identifying diagnostic genes and enzymes associated with these transformations. The linkage between shifts in microbiota composition, associated with diet and individual variation, and metabolite changes is being explored through theoretical modelling.