Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents

Abstract

Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.

Preservation by lyophilization of a human intestinal microbiota: influence of the cultivation pH on the drying outcome and re‐establishment ability

“…This may be due to different cultivation conditions in the study of Carvalho et al . ( 2021 , 2021 ) and this study that resulted in lower cell counts. Further, during freezing, intracellular ice can be formed and the increase in solute concentration imposes osmotic stress to the cell (Santivarangkna et al ., 2008 ).…”

“…So far, different approaches to enhance the FMT concept were tested for the treatment of C . difficile infections (Chiu et al ., 2021 ). The application of a processed, frozen and thawed donor stool resulted in recovery rates for CDI of up to 95% (Hamilton et al ., 2012 ; Smirnova et al ., 2019 ; Nicco et al ., 2020 ).…”

Effects of Dietary Supplementation with Protected Sodium Butyrate on Gut Microbiota in Growing-Finishing Pigs

“…It seems that the acidic environment generated by the PSB delivered to the distal part of the intestinal would have favored the presence of this bacterium. The positive effects of C. butyricum are well-known, and it has been used as a probiotic in cases of Clostridioides difficile infection or inflammatory bowel disease in humans [61,62]. It generates large amounts of butyrate through the fermentation of undigested dietary fibers and, as discussed before, this SCFA is associated with several beneficial effects, such as the improvement of the gastrointestinal barrier function, the modulation of intestinal immune homeostasis, or the reduction of inflammation [5,19].…”

Do Probiotics Prevent Clostridium difficile-Associated Diarrhea?

“…Chiu et al, in their study, reported that fecal microbiota transplantation's (FMT) mechanisms for effectively preventing or treating CDIs by modulating microbiota had been proposed to be through the influence on the metabolism of certain bile acids that affect C. difficile germination or vegetative growth [ 17 ].…”