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

Approximately 10% of individuals diagnosed with 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 , , , , , and , were depleted in non-remission patients. Moreover, , , and failed to colonize non-remission patients both pre- and post-treatment. Conversely, patients with a favorable FMT response exhibited a higher relative abundance of 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 , , and were frequently depleted in these lower effectiveness donors. Older patients were not conducive to the colonization of , 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.