Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.
Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Disease Models, Animal , Drug Therapy, Combination , Feces , Gastrointestinal Microbiome , Metronidazole , RNA, Ribosomal, 16S , Vancomycin , Animals , Metronidazole/administration & dosage , Vancomycin/administration & dosage , Vancomycin/pharmacology , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Gastrointestinal Microbiome/drug effects , Mice , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Clostridioides difficile/drug effects , Clostridioides difficile/genetics , RNA, Ribosomal, 16S/genetics , Feces/microbiology , Intestines/microbiology , Intestines/drug effects , Male , Bacteria/classification , Bacteria/genetics , Bacteria/drug effects , Metabolome/drug effects
There is a lack of clinical data to support the effectiveness and safety of postbiotics in the modulation of human oral microbiota and oral health care. Here, volunteers were recruited and randomly assigned to two cohorts: a placebo group (n = 15) and a postbiotic group (n = 16). The placebo group used toothpaste that did not contain postbiotics, while the postbiotic group used toothpaste with postbiotics (3 × 1010 CFU inactivated Lactobacillus salivarius LS97, L. paracasei LC86, and L. acidophilus LA85). Saliva samples were collected at different time points and the immunoglobulin A (IgA) and short-chain fatty acid (SCFA) levels were determined, while the salivary microbiota was analyzed by 16S rRNA amplicon sequencing. The results showed that salivary IgA levels and acetic and propionic acid levels were notably higher in the postbiotic group (P < 0.05), accompanied by an increase in the level of alpha diversity of the salivary microbiota, and these indexes remained high 1 month after discontinuing the use of toothpaste with or without postbiotics. A notable decrease in the relative abundance of the unclassified_Enterobacteriaceae, Klebsiella, Escherichia, etc. in the postbiotic group was accompanied by a notable increase in Ruminofilibacter and Lactobacillus. However, both groups did not cause significant changes in the overall structure of the host salivary microbiota. In conclusion, postbiotics dramatically and consistently improved oral immunity levels and SCFA content in the host. In addition, postbiotics were able to increase the level of microbial alpha diversity and down-regulate the abundance of some harmful microbes without significantly altering the structure of the host salivary microbiota. Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ) under the registration number ChiCTR2300074088.
Clostridioides difficile infection (CDI) is a serious disease with a high recurrence rate. The single and mixed biofilms formed by C. difficile in the gut contribute to the formation of recurrent CDI (rCDI). In parallel, other gut microbes influence the formation and development of C. difficile biofilms, also known as symbiotic biofilms. Interactions between members within the symbiotic biofilm are associated with the worsening or alleviation of CDI. These interactions include effects on C. difficile adhesion and chemotaxis, modulation of LuxS/AI-2 quorum sensing (QS) system activity, promotion of cross-feeding by microbial metabolites, and regulation of intestinal bile acid and pyruvate levels. In the process of C. difficile biofilms control, inhibition of C. difficile initial biofilm formation and killing of C. difficile vegetative cells and spores are the main targets of action. The role of symbiotic biofilms in CDI suggested that targeting interventions of C. difficile-promoting gut microbes could indirectly inhibit the formation of C. difficile mixed biofilms and improved the ultimate therapeutic effect. In summary, this review outlines the mechanisms of C. difficile biofilm formation and summarises the treatment strategies for such single and mixed biofilms, aiming to provide new ideas for the prevention and treatment of CDI.
