Desulfation of carrageenan by Bacteroides thetaiotaomicron fuels hydrogen sulfide production by Desulfovibrio desulfuricans.

Dietary carrageenan (CGN) is a widely used food additive, yet its microbial metabolism in the human gut and health implications remain unclear. This study elucidated a syntrophic pathway wherein Bacteroides thetaiotaomicron (B. theta) degrades CGN via specific sulfatases and glycoside hydrolases, releasing inorganic sulfate. This sulfate fuels the growth and metabolic activity of the sulfate-reducing bacterium Desulfovibrio desulfuricans (D. desulfuricans). In vitro co-culture experiments demonstrated that this cross-feeding interaction significantly enhanced hydrogen sulfide (H2S) production. Transcriptomic and metabolomic analyses revealed that CGN, particularly κ-type, upregulated B. theta genes encoding key desulfation and depolymerization enzymes. Concurrently, D. desulfuricans showed increased expression of genes in the dissimilatory sulfate reduction pathway (sat, aprAB, dsr), accompanied by marked accumulation of pathway intermediates and H2S. Furthermore, co-culture altered microbial glycerophospholipid metabolism and inhibited bacterial cysteine synthesis. Our findings uncover a defined CGN-mediated metabolic cross-feeding partnership between gut bacteria that enhances H2S production in vitro. This mechanism provides a microbial basis for understanding how dietary CGN may influence intestinal sulfate metabolism and H2S production.