Gut microbiota and sulfur compounds in CKD

Chronic Kidney Disease (CKD) is characterized by a systemic metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The underlying factors contributing to this metabolic imbalance are not yet fully understood. Here, we evaluated the relationship between gut microbiota dysbiosis and alterations in H2S and lanthionine concentrations in CKD. The gut microbiota of 88 CKD patients (non-dialyzed CKD, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and HPLC/MS, respectively. The relationship between microbial abundance and metabolic profile was assessed through multivariate Pearson's correlation. The CKD population exhibited a tenfold increase in serum lanthionine concentrations associated with kidney dysfunction and uremic toxicity. In contrast, hemodialysis and transplant patients had lower serum H2S than healthy controls, related to lanthionine retention. Fecal H2S levels were not altered or related to circulating concentrations, whereas fecal lanthionine was significantly increased in the CKD population compared to healthy controls and linked to lanthionine retention and uremic toxicity in circulation. Gut microbiota analysis revealed differences in beta diversity compared to healthy individuals, with species such as Streptococcus salivarius less abundant in non-dialyzed CKD patients, Christensenella minuta and Negativibacillus massiliensis more abundant in hemodialysis patients, and Ruminococcus gnavus more abundant in transplant patients. No correlation was detected between differentially abundant species and the metabolic profile that could explain the alterations in H2S and lanthionine concentrations. Other species, including Fusicatenibacter saccharivorans, Bacteroides caccae, and Lachnospira pectinoschiza correlated with the metabolites' concentrations. H2S and lanthionine deregulation could not be attributed to gut microbiota dysbiosis but to kidney dysfunction and related uremic toxicity. Further research is required to evaluate the potential beneficial role of identified bacterial species in modulating H2S/lanthionine homeostasis in CKD.