Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies

Abstract

Bacterial metabolism plays a fundamental role in gut microbiota ecology and host-microbiome interactions. Yet the metabolic capabilities of most gut bacteria have remained unknown. Here we report growth characteristics of 96 phylogenetically diverse gut bacterial strains across 4 rich and 15 defined media. The vast majority of strains (76) grow in at least one defined medium, enabling accurate assessment of their biosynthetic capabilities. These do not necessarily match phylogenetic similarity, thus indicating a complex evolution of nutritional preferences. We identify mucin utilizers and species inhibited by amino acids and short-chain fatty acids. Our analysis also uncovers media for in vitro studies wherein growth capacity correlates well with in vivo abundance. Further value of the underlying resource is demonstrated by correcting pathway gaps in available genome-scale metabolic models of gut microorganisms. Together, the media resource and the extracted knowledge on growth abilities widen experimental and computational access to the gut microbiota.

Fast automated reconstruction of genome-scale metabolic models for microbial species and communities

“…In this regard, one major hurdle is the characterization of gut bacterial species in terms of growth requirements and metabolic potential. In a recent study from our group, the growth of 96 phylogenetically diverse gut bacteria was characterized across 19 different media (15 defined and 4 complex media compositions) (43). From this list, a total of 47 bacteria are also included in the AGORA collection, a recently published collection of 773 semi-manually curated models of human gut bacteria (57).…”

“…The reconstructions were performed using the genome sequences and growth media provided in (43). The uptake/secretion data collected by (44) were provided as soft constraints during reconstruction (note that these data are reported at species, rather than strain level, hence the confidence level is low).…”

High-throughput isolation and sorting of gut microbes reduce biases of traditional cultivation strategies

“…Finally, here we loaded droplets with three different rich media in order to broadly enrich the cultivated community representation across taxa. However, some bacteria prefer defined media over rich media [12] while others utilize surface features such as hydrophobicity, roughness, and surface chemistry to form biofilms and proliferate [42]. Further enrichment of anaerobic organisms within our droplet platform could be achieved by incorporating droplet generation with defined media [11], combinatorially generated gradients of media [43], or varying the droplet surfactant chemistries to improve biofilm formation [44].…”

“…In recent years, numerous cultivation strategies have been developed to increase the throughput in isolating and studying gut-associated bacteria. For example, a recent well plate-based growth experiment screened 96 phylogenetically diverse human gut-associated bacterial strains across 19 media and determined their nutritional preferences and biosynthetic capabilities [12]. Another study that relied on 'SlipChip' [13], a microfluidic device that can isolate hundreds of microbial cells and enable targeted cultivation, successfully recovered an organism that was a member of the genus Oscillibacter [14].…”

Metabolic cross-feeding allows a gut microbial community to overcome detrimental diets and alter host behaviour

“…Adding to this complexity, in humans the impact of diet on the microbiome is highly personalized (Johnson et al, 2019). While in vitro experiments have started to systematically disentangle the nutritional preferences of single human gut microbes (Tramontano et al, 2018), we are very far from achieving a coherent mechanistic picture of how bacterial dietary needs shape the microbiome and its capacity to influence the host. Given the large number of nutrients required by the host and the nutritional complexity of natural foods, identifying how single nutrients affect the microbiome and hence the host, remains a key challenge in current microbiome research.…”