Professor Harry Flint

Professor_Harry_Flint

Professor Harry Flint

Role of gut microorganisms in nutrition and health

Fibre and other slowly-digested carbohydrates that are found mainly in plant-based foods make important contributions to human health. These are thought to include helping to maintain gut health and prevent cancer, heart disease and diabetes. Much of their influence occurs through effects on the complex microbial community that colonises our large intestine.

Our research is uncovering the impact of plant fibre and resistant starch on the species composition and metabolism of human gut micro-organisms. This will help us to optimise dietary approaches to benefit human health, including collaborating with plant breeders to identify and develop varieties that maximise health benefits.


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).

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).

 

Research team

Dr Sylvia Duncan - Research Fellow

Dr Indrani Mukhopadhya - Research Fellow

Dr Paul O Sheridan - Research Fellow

Dr Dinesh Thapa - Research Fellow

Dr Eva Soto- Research Fellow

Faith Chung - Post Graduate student


 


Scottish Government RESAS

  • RESAS themed programme 2011-2016: RINH representative for Food theme (5); Coordinator for WP5.2.RD3.
  • Scottish Government Strategic Partnership project with U. Glasgow on SCFA and satiety [2012-2016]

BBSRC funding

  • Research project grant BB/L009951/1 – ‘Uncovering the molecular strategies that allow human gut symbionts to degrade insoluble dietary and host glycans’ (3 year project due to start in 2014. Part of a collaborative project (Harry Flint - principal applicant) with Dr Nathalie Juge, IFR, Norwich)
  • BBSRC CASE PhD studentship. (2012-2016)-  ‘Development of new targeted prebiotic approaches for optimizing the human intestinal microbiota’ Industrial partner, Cargill (Dr Douwina Bosscher); UoA supervisors Harry Flint and Sylvia Duncan.

EU projects 

  • EU FP7 SATIN (2012-2016) “Satiety control through food structures..” (18 partners - U Aberdeen component £691,343) (with Alex Johnstone). Work package leader.
  • EU FP7 FibeBiotics (2012-2017) “Dietary fibers supporting gut and immune function..” (17 partners  - U Aberdeen component  £300,000) (with Petra Louis).

 

 


  • Moraïs, S., Cockburn, DW., Ben-David, Y., Koropatkin, NM., Martens, EC., Duncan, SH., Flint, HJ., Mizrahi, I. & Bayer, EA. 'Lysozyme activity of the Ruminococcus champanellensis cellulosome'. Environmental Microbiology.
    [Online] DOI: 10.1111/1462-2920.13501
  • Duncan, SH., Russell, WR., Quartieri, A., Rossi, M., Parkhill, J., Walker, AW. & Flint, HJ. (2016). 'Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid'. Environmental Microbiology, vol 18, no. 7, pp. 2214-2225.
    [Online] DOI: 10.1111/1462-2920.13158
    [Online] AURA: Duncan_et_al_2016_Environmental_Microbiology.pdf
  • Walker, AW. & Flint, HJ. (2016). 'Editorial: further evidence that proton pump inhibitors may impact on the gut microbiota'. Alimentary Pharmacology & Therapeutics, vol 43, no. 10, pp. 1104-1105.
    [Online] DOI: 10.1111/apt.13596
  • Widder, S., Allen, RJ., Pfeiffer, T., Curtis, TP., Wiuf, C., Sloan, WT., Cordero, OX., Brown, SP., Momeni, B., Shou, W., Kettle, H., Flint, HJ., Haas, AF., Laroche, B., Kreft, J-U, Rainey, PB., Freilich, S., Schuster, S., Milferstedt, K., van der Meer, JR., Groszkopf, T., Huisman, J., Free, A., Picioreanu, C., Quince, C., Klapper, I., Labarthe, S., Smets, BF., Wang, H., Soyer, OS. & Isaac Newton Institute Fellows 'Challenges in microbial ecology: building predictive understanding of community function and dynamics'. The ISME Journal.
    [Online] DOI: 10.1038/ismej.2016.45
  • Sheridan, PO., Martin, JC., Lawley, TD., Browne, HP., Harris, H., Bernalier-Donadille, A., Duncan, SH., O'Toole, PW., Scott, KP. & Flint, HJ. (2016). 'Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes'. Microbial Genomics, vol 2, no. 2, 43.
    [Online] DOI: 10.1099/mgen.0.000043
    [Online] AURA: mgen000043.pdf
  • Morais, S., David, YB., Bensoussan, L., Duncan, SH., Koropatkin, NM., Martens, EC., Flint, HJ. & Bayer, EA. (2016). 'Enzymatic profiling of cellulosomal enzymes from the human gut bacterium, Ruminococcus champanellensis, reveals a fine-tuned system for cohesin-dockerin recognition'. Environmental Microbiology, vol 18, no. 2, pp. 542-556.
    [Online] DOI: 10.1111/1462-2920.13047

Research briefs for the Knowledge Scotland web site

EU projects

Satin – is a project funded by the European Union Seventh Framework Programme (FP7/2011-2016) under grant agreement n° 289800 to examine Satiety Innovation. This project will examine novel food ingredients on appetite control, with links with the food industry.

Invited Lectures (2010-11) - Harry Flint

  • International Microbiome consortium meeting (MetaHIt), Shenzhen China. March 2010
  • ASM Beneficial Microbes symposium, Miami USA. October 2010.
  • Gut Day, Ghent. October 2010
  • The Role of Microorganisms in Adaptation and Evolution of Humans, Animals and Plants. Meeting to be held in Israel. March 2011
  • The Microbiota in Health and Disease – meeting to be held at Yale University USA. April 2011
  • Today’s Science Tomorrow’s Medicine meeting in Stockholm. October 2011

Additional Activities

Harry Flint is an Associate Editor for Microbiology, and is on the editorial boards of Environmental Microbiology, FEMS Microbiology Ecology and Gut Microbe. Both he and Sylvia Duncan are regular reviewers for a wide range of journals.

Harry Flint is a member of the UK Advisory Committee on Novel Foods and Processes (ACNFP) and was a member of the Organizing Committee for the Rowett-INRA 2010 conference held in Aberdeen

Book Chapters

  • Flint HJ, Duncan SH and Louis P (2009). Gut Microbial Ecology. In Designing Functional Foods ed McClements DJ & Decker EA. Pp. 38-67. Woodhead Publishers.
  • Flint HJ, Duncan SH (2010) Response of the human colonic microbiota to dietary change. Old Herborn University Symposium Monograph No 22
  • Flint HJ, Duncan SH  (2010) Prebiotics and fiber. In ”Probiotics and Prebiotics” - Floch & Kim (ed)
  • Miller MEB, Brulc JM, Bayer EA, Lamed R, Flint HJ, White BA (2009). Advanced technologies for biomass hydrolysis and saccharification using novel enzymes. In Biomass to biofuels: strategies for global industries. Wiley & Sons.
  • Flint HJ, Wallace RJ. (2010). Obesity and colorectal cancer risk: impact of the gut microbiota and weight-loss diets.  Open Obesity Journal.