Combining sequence-based approaches with anaerobic microbiology and modelling to understand gut microbial communities

Gut micro-organisms possess biochemical capabilities that far exceed those of their mammalian hosts, particularly in the ability to gain energy from the breakdown of diet-derived plant material (fibre). This article reviews investigations into gut microbial communities conducted by Harry Flint and his research group. First, extracellular cellulosome and amylosome enzyme complexes were found to mediate the breakdown of plant cell walls and resistant starch by specialised Firmicutes bacteria, both in the human colon and in the rumen. In contrast, Bacteroidetes (Bacteroides, Prevotella spp.) rely on their ability to capture soluble carbohydrates. Human dietary studies examining the impact of fibre sources upon microbiota composition and metabolism identified 'diet-responsive' species. In addition, dominant species of butyrate-producing bacteria, including a subset able to convert lactate to butyrate, were isolated from healthy human volunteers. Most produce butyrate from carbohydrates via butyryl-CoA:acetate CoA-transferase, with uptake of external acetate, while lactate conversion is associated with a highly inducible gene cluster (lct). In pH-controlled chemostat studies, mildly acid pH depressed growth of propionate-producing Bacteroidetes, but favoured butyrate production by Firmicutes. This may explain why % butyrate among SCFA increases with total faecal SCFA concentration in human studies. Although lactate is normally consumed by lactate-utilising bacteria, destabilisation of the microbial community associated with lactate accumulation can result in radically altered microbiota and metabolite profiles. A theoretical model based on microbial functional groups (MFG) was developed to better understand community dynamics. Consequences for nutritional research of our expanding knowledge of the microbial ecology of the human gut are considered.