Supervisor: Dr Alan Walker

The human gut is home to an extremely diverse and abundant collection of microbes, collectively referred to as the "intestinal microbiota", which has significant impacts on our health. Recent microbiota analyses have identified strong anti-correlations between two important constituent genera, the Bacteroides and Prevotella (1,2). Intriguingly, it appears that Prevotella are highly dominant colonisers of individuals from agrarian societies whereas, in contrast, individuals from urbanised societies are more commonly colonised by Bacteroides (3,4). It is assumed that diet plays an important role in this, with Prevotella apparently favoured by diets high in fibre/polysaccharides, while Bacteroides appear to be promoted by diets high in animal fats and protein (2).

The health consequences of having an intestinal microbiota that is dominated by either Prevotella or Bacteroides are currently unknown. Elevated Bacteroides levels have previously been implicated in numerous disorders, while Prevotella abundance is anti-correlated with diarrhoeal disease in African children (5). In contrast, another recent study correlated intestinal Prevotella spp. with susceptibility to the development of arthritis (6).

In this project we will seek to explain why there is an inverse correlation between Bacteroides and Prevotella species within the human colon. The student will survey the intestinal microbiota from human volunteers (from both agrarian and urbanised societies) to identify individuals harbouring each of these bacterial groups. They will isolate and characterise human Prevotella and Bacteroides strains from faecal samples, and will carry out a programme of experiments in vitro to determine favourable growth conditions/dietary substrates for each group. Co-culturing experiments will determine whether or not these two groups are truly antagonistic or merely favoured by the prevailing diet of the host. If diet is shown to be the predominant driver of Bacteroides/Prevotella dominance this paves the way for future studies exploring interventions aimed at improving human health (7).

References:

  1. Arumugam, M. et al. (2011). Enterotypes of the human gut microbiome. Nature 473:174-80.
  2. Wu, G.D. et al. (2011). Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105-8.
  3. De Filippo, C. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. PNAS 107:14691-6.
  4. Cooper, P. et al. (2013). Patent human infections with the whipworm, Trichuris trichiura, are not associated with alterations in the faecal microbiota. PLoS ONE  8:e76573.
  5. Pop, M et al. (2014). Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition. Genome Biology 15, R76
  6. Scher, J.U. et al. (2013). Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202.
  7. Cotillard, A. et al. (2013). Dietary intervention impact on gut microbial gene richness. Nature500:585-8.

Research training:

The lab has extensive experience of working with intestinal bacteria, and we maintain a diverse collection of cultured isolates, incorporating a number of key species. The group is fully equipped to perform anaerobic microbiology, with access to techniques such as fermentor model systems, proteomics and mass spec facilities, DNA sequencing, qPCR and FISH. The student would receive training in anaerobic culturing, DNA analysis (isolation, PCR, handling of large datasets such as 16S rRNA gene surveys/genome sequences), and metabolite analyses.

Essential background required by the student:

First / second degree (or equivalent experience):

  • Minimum of a good UK 2.1 honours degree (or international equivalent) in a relevant subject area (e.g. microbiology, genetics, molecular biology)

Knowledge of:

  • General background in microbiology, genomics, bioinformatics or nutrition would be an advantage.