Diversity and distribution of sulfur metabolism in the human gut microbiome and its association with colorectal cancer

Abstract

Microbial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human gut using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates, however the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr). Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut. Here we show that microbial sulfur metabolism is more abundant and diverse than previously studied and is statistically associated with CRC. Using ~17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, anaerobic sulfite reductases were twice as abundant as dsr. We identified twelve potential pathways for reductive taurine metabolism including novel pathways, and prevalence of organic sulfur metabolic genes indicate these substrates may be the most abundant source of microbially derived H2S. Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut, and highlight key gaps that limit understanding of its potential contributions to the pathogenesis of CRC.

Populational genomic insights of Paraclostridium bifermentans as an emerging human pathogen

“…Particularly, group_a plasmids, which are present in one-third of P.b strains, carry virulence genes, as well as several organic metabolism and biosynthesis genes (Figure 6A). For instance, corC coded functions for magnesium and cobalt efflux (Huang et al, 2021); tlyC coded functions for phagosomal escape (Whitworth et al, 2005); asrABC-nirC cluster coded functions for microbial sulfidogenesis, which produces genotoxic hydrogen sulfide as a potential trigger of colorectal cancer (Czyzewski and Wang, 2012;Wolf et al, 2022). Of note, the rarely appearing group_f plasmids in P.b encoded two types of mosquito toxins (i.e., the Cry16Aa/ Cry17Aa pair, and the novel neurotoxin PMP1) that are carried only by two strains isolated from Malaysia and Brazil, which are geographically distant but populated with mosquito species, indicating a gene Representative plasmid groups in P. bifermentans and their coded functions.…”