Depletion of butyrate-producing microbes of the Firmicutes predicts nonresponse to FMT therapy in patients with recurrent Clostridium difficile infection.

Approximately 10% of individuals diagnosed with Clostridium difficile infection (CDI) show the resistance to fecal microbiota transplantation (FMT), with the underlying mechanisms remaining elusive. Deciphering the intricate microbiome profile within this particular subset of FMT-refractory patients via clinical FMT investigations assumes paramount importance, as it holds the key to designing targeted therapeutic interventions tailored for CDI, particularly recurrent CDI (rCDI). A cohort of twenty-three patients afflicted with rCDI, exhibiting congruent clinical baselines, was meticulously selected for FMT. Rigorous screening of thousands of healthy individuals identified ten FMT donors who met stringent health standards, while a total of 171 stool samples were collected to serve as healthy controls. To assess the influence of microbiome dynamics on FMT efficacy, fecal samples were collected from four donors over a continuous period of twenty-five weeks. After FMT treatment, seven individuals exhibited an inadequate response to FMT. These non-remission patients displayed a significant reduction in α-diversity indexes. Meanwhile, prior to FMT, the abundance of key butyrate-producing Firmicutes bacteria, including Christensenellaceae_R_7_group, Ruminococcaceae_unclassified, Coprococcus_2, Fusicatenibacter, Oscillospira, and Roseburia, were depleted in non-remission patients. Moreover, Burkholderiales_unclassified, Coprococcus_2, and Oscillospira failed to colonize non-remission patients both pre- and post-treatment. Conversely, patients with a favorable FMT response exhibited a higher relative abundance of Veillonella prior to treatment, whereas its depletion was commonly observed in non-remission individuals. Genera interactions in lower effectiveness FMT donors were more similar to those in non-remission patients, and Burkholderiales_unclassified, Coprococcus_2, and Oscillospira were frequently depleted in these lower effectiveness donors. Older patients were not conducive to the colonization of Veillonella, consistent with their poor prognosis after FMT. FMT non-remission rCDI patients exhibited distinct characteristics that hindered the colonization of beneficial butyrate-producing Firmicutes microbes. These findings hold promise in advancing the precision of FMT therapy for rCDI patients.

Gut Metagenome as a Potential Diagnostic and Predictive Biomarker in Slow Transit Constipation.

Slow transit constipation (STC) is one of the most frequent gastrointestinal diagnoses. In this study, we conducted a quantitative metagenomics study in 118 Chinese individuals. These participants were divided into the discovery cohort of 50 patients with STC and 40 healthy controls as well as a validation cohort of 16 patients and 12 healthy controls. We found that the intestinal microbiome of patients with STC was significantly different from that of healthy individuals at the phylum, genus, and species level. Patients with STC had markedly higher levels of Alistipes and Eubacterium and lower abundance of multiple species belonging to the Roseburia genus. Patients with STC gene expression levels and the Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology pathway (such as fatty acid biosynthesis, butanoate metabolism, and methane metabolism pathways) enrichment were also substantially different from those of healthy controls. These microbiome and metabolite differences may be valuable biomarkers for STC. Our findings suggest that alteration of the microbiome may lead to constipation by changing the levels of microbial-derived metabolites in the gut. Above findings may help us in the development of microbial drugs.