Linking diet to intestinal microbial communities and host health

The human large intestine is home to a complex and highly abundant collection of microbes (termed the intestinal microbiota). These microbes have numerous beneficial impacts on human health, ranging from the release of health-promoting products, to protection from invading pathogens and stimulation of host immune responses. Conversely, some intestinal microbes can have detrimental effects, so it is important to establish what constitutes a healthy microbiota, identify particularly beneficial or harmful species, and learn how to alter these microbial communities in order to benefit human health. Crucially, the composition and activities of the intestinal microbiota can be heavily influenced by what we eat.
 
In our lab we combine anaerobic microbiology with state of the art DNA sequencing technologies in order to shed light on interactions between host diet and the intestinal microbiota, and how these factors may contribute to chronic ailments.

Research focus

Microbiota research has been revolutionised in recent years by the advent of modern DNA sequencing technologies. These allow large-scale, in-depth studies, greatly expanding our ability to monitor the microbiota and how it responds to host behaviour such as changes in diet. However, traditional microbiology techniques such as anaerobic culture also remain highly relevant, and help us to understand the functional roles that individual members of the microbiota may play in the intestines. In our lab we combine DNA sequence analysis and microbiological approaches to generate novel insights into the intestinal microbiota. We are aided in this by long standing collaborations with many other international research groups, and with The Wellcome Trust Sanger Institute in Cambridge, UK.
 
Recent work has shown striking global divergence in intestinal microbiota composition, with individuals from developing countries harbouring distinct microbes from those found in individuals from more urbanised societies. This may have fundamental implications for what we class as a "healthy" microbiota here in the West, and is thought to be largely driven by host diet. Typical Western diets, rich in refined carbohydrates, fats and proteins and low in fibre, are fundamentally different to those consumed in more agrarian societies, where people tend to consume more fibre-rich diets. Working with collaborators in both the UK and in developing countries we are trying to understand how consuming disparate diets results in the development of different intestinal microbiota compositions, and how this impacts host health.
 
A better understanding of the health impacts of fibre-rich versus more processed foods should lead to improved dietary advice, and allow us to identify potentially beneficial novel bacterial species.
 
A further research interest is in identifying key functional groups of bacteria within the intestinal microbiota. Although the microbiota is an extremely complex entity, with many species sharing overlapping functional capabilities, it is thought that some deleterious or beneficial activities are limited to a relatively small range of species. In particular, we are interested in microbial contributors to the development of chronic ailments. For example, we are interested in bacterial consumers of lactate, accumulation of which has been linked to chronic diseases such as inflammatory bowel disease.
 
Determining key functional groups of bacteria is a critical step towards microbiota-based therapeutics.

Research team:

Gillian Donachie – Research assistant

Paul Sheridan - Research Fellow

Tim Snelling - Research Fellow

Elena Conti - PhD Student

Liviana Ricci - PhD Student

Grants

Research Grants

2014-2021      
Supported by institutional core funding from the Scottish Government’s Rural and Environmental Science and Analysis Service (RESAS).

2015-2017      
Exploiting the microbiome to prevent and treat human diseasesChr. Hansen. [Co-PI with Harry Flint]

2016-2017      
Microbiome and metagenomic study of the rumen microbial population and their microbial enzyme genes. RESAS. [PI]

2016-2020       
Mechanisms underpinning the links between diet, the intestinal microbiota and health. 
Princess Royal Tenovus Scotland Medical Research Scholarship. [PI]

2016-2020      
Uncovering the impact of diet-responsive gut microbes on host health.  RESAS PhD Studentship. [PI]

 

Selected Past Funding

2010-2014      
Microbial community ecology of chronic respiratory infectionsNERC CASE Studentship. [Co-I: Christopher van der Gast was PI]

2011-2014      
Immunological and microbiological effects of fecal transplantation in chronic pouchitisBroad Foundation. [Co-I: Ailsa Hart was PI]

2011-2013       
The gut microbiota and NOD2 genotype in Crohn’s disease: a pilot study for the UKIBD Microbiota Consortium
Core – The Digestive Disorders Foundation. [Co-I: Charlie Lees was PI].

2015                
Impact of the gut microbiota and diet upon 
Candida colonisation and infectionWellcome Trust ISSF@Aberdeen Seed Corn award. [Co-I: Al Brown was PI].

 

Publications
  • Quince, C., Walker, AW., Simpson, JT., Loman, NJ. & Segata, N. (in press). 'Shotgun metagenomics, from sampling to sequencing and analysis'. Nature Biotechnology.
  • Depner, M., Ege, MJ., Cox, MJ., Dwyer, S., Walker, AW., Birzele, LT., Genuneit, J., Horak, E., Braun-Fahrländer, C., Danielewicz, H., Maier, RM., Moffatt, MF., Cookson, WO., Heederik, D., von Mutius, E. & Legatzki, A. (2017). 'Bacterial microbiota of the upper respiratory tract and childhood asthma'. Journal of Allergy and Clinical Immunology, vol 139, no. 3, pp. 826–834.
    [Online] DOI: 10.1016/j.jaci.2016.05.050
  • Elliott, DRF., Walker, AW., O’Donovan, M., Parkhill, J. & Fitzgerald, RC. (2017). 'A non-endoscopic device to sample the oesophageal microbiota: a case-control study'. The Lancet Gastroenterology & Hepatology, vol 2, no. 1, pp. 32-42.
    [Online] DOI: 10.1016/S2468-1253(16)30086-3
    [Online] AURA: microbiome_Lancet_Gastro_revised2_accept_changes_Lancet_1_.d...
  • 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
  • Pop, M., Paulson, JN., Chakraborty, S., Astrovskaya, I., Lindsay, BR., Li, S., Corrada Bravo, H., Harro, C., Parkhill, J., Walker, AW., Walker, RI., Sack, DA. & Stine, OC. (2016). 'Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment'. BMC Genomics, vol 17, 440.
    [Online] DOI: 10.1186/s12864-016-2777-0
    [Online] AURA: art_3A10.1186_2Fs12864_016_2777_0.pdf
  • Cuthbertson, L., Rogers, GB., Walker, AW., Oliver, A., Green, LE., Daniels, TWV., Carroll, MP., Parkhill, J., Bruce, KD. & van der Gast, CJ. (2016). 'Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention'. The ISME Journal, vol 10, no. 5, pp. 1081-1091.
    [Online] DOI: 10.1038/ismej.2015.198
    [Online] AURA: ismej2015198a.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
  • Torondel, B., Ensink, JHJ., Gundogdu, O., Ijaz, UZ., Parkhill, J., Abdelahi, F., Nguyen, V-A, Sudgen, S., Gibson, W., Walker, AW. & Quince, C. (2016). 'Assessment of the influence of intrinsic environmental and geographical factors on the bacterial ecology of pit latrines'. Microbial Biotechnology, vol 9, no. 2, pp. 209-223.
    [Online] DOI: 10.1111/1751-7915.12334
    [Online] AURA: PitLatrines_CrossSectional_Torondel_et_al_2016_Microbial_Bio...
Additional activities

Teaching Responsibilities

Lectures/Tutorials

  • Molecular Nutrition, RR5501
  • Introduction to Microbiology, MC5008
  • Molecular Microbiology, MC3504
  • Mothur Workshop (Bioinformatics training workshop) 

Associate Fellow of the Higher Education Authority – June 2015 to Present


  • Senior Editor for the journal Microbial Genomics
  • Associate Editor for the journal Microbiome