Differential hydrogen sulfide production by a human cohort in response to animal- and plant-based diet interventions

Background: Hydrogen sulfide (H₂S) is a toxic end-product of microbial fermentation produced in the colon that may play a role in the pathogenesis of several diseases, including ulcerative colitis and colon cancer. However, the effect of diet interventions on intestinal burden of H₂S gas exposure remains poorly understood. Objective: Determine the effect of short-term (1-week) plant- and animal-based eating patterns on ex vivo fecal H₂S production in healthy human volunteers. Methods: The study design was an open-label, cross-over diet study and diets were self-administered. Each participant consumed two interventional diets: 1) an animal-based, low fiber (i.e. western) diet and 2) a plant-based, high fiber diet, separated by a two-week washout period. Participants collected full stool samples at the end of each week, which were processed within 2 h of collection to capture H₂S production. Microfluidic qPCR (MFQPCR) was used to simultaneously quantify multiple taxonomic and functional groups involved in sulfate reduction and the fecal microbiota was characterized through high-throughput DNA sequencing. Results: Median H₂S production was higher following the animal-based diet compared to the plant-based diet (p = 0.02; median difference 29 ppm/g, 95% CI 16–97). However, there was substantial individual variability and 2 of 11 individuals (18%) produced more H₂S on the plant-based diet. Using the top and bottom quartiles of H₂S percent change between animal- and plant-based diet weeks to define responders and non-responders, significant taxonomic differences were observed between the responder and non-responder cohorts. Conclusions: Here we report that substrate changes associated with a 1-week plant-based diet intervention resulted in lower ex vivo H₂S production compared to a 1-week animal-based diet intervention in most healthy individuals. However, H₂S responsiveness to diet was not uniform across the entire cohort, and potential H₂S production enterotypes were characterized that may predict individualized H₂S responsiveness to diet.