Sulfur metabolism in human gut microbiota

Sulfur acquisition is crucial to both humans and their symbiotic gasterointestinal tract (GI tract) microbiota. The colonic sulfur-containing compounds are either inorganic (e.g. sulfate, sulfite) or organic (e.g. dietary amino acids, bile and mucins). When it is not assimilated, the end product of the anaerobic microbial degradation of sulfur-compounds is predominantly hydrogen sulfide (H2S). Gastrointestinal H2S is a neuromodulator and plays a critical role in controlling physiological responses such as motility and epithelial cell health. It has also been suggested that H2S has a potential pathogenic role, such as in inflammatory bowel disease, which afflicts 0.1–0.5% of individuals in western countries. The exact role and fate of sulfide in the human GI tract is not clear and until now, there are only few sulfidogenic microorganisms described that use sulfate or sulfite as terminal electron acceptor, such as Desulfovibrio spp. or Bilophila spp. (via taurine).

During the last decade ‘meta-omics’ projects have greatly advanced our knowledge of the human microbiome and its specific role in governing health and disease states. Abundant functional and taxonomical information has been generated under the preview of these large projects and stored in public databases (KEGG, COG, MG-RAST). These databases serve as a resource for searching metabolic pathways of microbes in the human GI tract. We will use these resources for mining pathways and search for novel features of the GI tract microbiome. We will direct our analysis towards sulfur-related pathways present in existing metagenomes and metatransciptomics datasets, where both functional and taxonomic information can be generated. This meta-analysis will assist in identifying which intestinal bacteria are involved in the sulfur-related pathways. In addition, we will search for different and potential novel pathways for sulfur metabolism in the GI tract.

In the meanwhile, it is necessary to bring more microorganisms in laboratory culture to enable further studies on their eco-physiology in relation with the gut health. Isolation of novel sulfur-utilizers from anaerobic gut ecosystems will be performed on the stool samples of one healthy control and one IBS patient. Enrichments will be designed with different electron donors (e.g. lactate, H2, taurine, and cysteine) and acceptors (sulfate and sulfite). Once the isolates are obtained, a genome-guided characterization and metabolic pathway reconstruction will be performed to link the isolated microorganisms with their role in the GI tract.