Intestinal sulfate-reducing bacteria (SRB) growth and resultant hydrogen sulfide production may damage the gastrointestinal epithelium and thereby contribute to chronic intestinal disorders. However, the ecology and phylogenetic diversity of intestinal dissimilatory SRB populations are poorly understood, and endogenous or exogenous sources of available sulfate are not well defined. The succession of intestinal SRB was therefore compared in inbred C57BL/6J mice using a PCR-based metabolic molecular ecology (MME) approach that targets a conserved region of subunit A of the adenosine-5-phosphosulfate (APS) reductase gene. The APS reductase-based MME strategy revealed intestinal SRB in the stomach and small intestine of 1-, 4-, and 7-day-old mice and throughout the gastrointestinal tract of 14-, 21-, 30-, 60-, and 90-day-old mice. Phylogenetic analysis of APS reductase amplicons obtained from the stomach, middle small intestine, and cecum of neonatal mice revealed that Desulfotomaculum spp. may be a predominant SRB group in the neonatal mouse intestine. The toxic gas hydrogen sulfide (H 2 S) is generated from sulfate during anaerobic respiration by sulfate-reducing Archaea and Bacteria (21, 58). A possible link between H 2 S and chronic intestinal disorders has been evoked by data indicating increased numbers of intestinal sulfate-reducing bacteria (SRB) and rates of sulfidogenesis in inflammatory bowel disease (IBD) patients compared to healthy humans (12, 37). Hydrogen sulfide selectively impairs the oxidation of n-butyrate by colonic epithelial cells (42). Because membrane lipid biosynthesis, ion absorption, mucin synthesis, and detoxification processes in colonocytes depend on the oxidation of n-butyrate, diminished n-butyrate metabolism is likely to compromise the epithelial cell barrier (42). Sulfide-induced damage of the epithelial barrier function would promote translocation of bacterial and food antigens, resulting in local inflammatory responses to normally benign antigens, an outcome consistent with histopathological features of IBD (16, 61). Chronic exposure to H 2 S might also perturb normal cycles of epithelial renewal in the intestine, thereby predisposing to proliferative disorders such as colon cancer.Intestinal sulfate can be derived either from exogenous sources, namely sulfate in drinking water and dietary foodstuffs, or from endogenous sources such as sulfated mucins (sulfomucins), sulfate-conjugated bile, and chondroitin sulfate. Use of chemically bound, endogenous sulfate by SRB is facilitated through interactions with sulfatase-harboring bacteria (e.g., Bacteroides spp. [56]). Most goblet cells, a differentiated epithelial cell subtype that produces mucins, generate sulfomucins (22). The degree of sulfation, however, increases from proximal to distal segments of the intestine and is highest in those segments harboring dense bacterial populations, such as the cecum and colon (9,20).The ecology and taxonomy of intestinal SRB and their metabolic activities remain uncharacterized. Most studies of...