scholarly journals Alteration of Intestinal Microbiome of Clostridioides difficile-Infected Hamsters during the Treatment with Specific Cow Antibodies

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 724
Author(s):  
Hans-Jürgen Heidebrecht ◽  
Ilias Lagkouvardos ◽  
Sandra Reitmeier ◽  
Claudia Hengst ◽  
Ulrich Kulozik ◽  
...  

Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to the standard application of nonspecific antibiotics. To gain a deeper understanding of the role of the microbiome in the treatment of CDI with bovine antibodies, stool and intestinal fluid samples of hamsters were collected in large quantities from various treatments (>400 samples). The results show that the regeneration of the microbiome instantly begins with the start of the antibody treatment, in contrast to the Vancomycin-treated group where the diversity decreased significantly during the treatment duration. All antibody-treated hamsters that survived the initial phase also survived the entire study period. The results also show that the regeneration of the microbiome was not an antibody-induced regeneration, but a natural regeneration that occurred because no microbiota-inactivating substances were administered. In conclusion, the treatment with bovine antibodies is a functional therapy for both the acute treatment and the prevention of recurrence in hamsters and could meet the urgent need for CDI treatment alternatives in humans.

2021 ◽  
Vol 14 (01) ◽  
pp. 016-020
Author(s):  
Juliana Peloso Signorette ◽  
Rômulo Tadeu Dias de Oliveira ◽  
José Maria Montiel ◽  
Priscila Larcher Longo

Abstract Objective This study aimed to perform a comprehensive review of clinical trials using fecal microbiota transplantation in cases of Clostridioides difficile infection. Methods This manuscript reviews clinical studies published from 2003 to 2020 at the Scientific Electronic Library Online (SciELO Brazil), Latin American and Caribbean Health Sciences Literature (LILACS) and US National Library of Medicine (MedLine/PubMed) databases using the descriptors antibiotic/antimicrobial, Clostridium difficile/Clostridioides difficile, intestinal microbiota/intestinal microbiome and fecal transplantation. Results Interventions on microbiota include the use of probiotics, prebiotics, and fecal microbiota transplantation as therapeutic methods. Results show that fecal microbiota transplantation is an excellent alternative for the treatment of recurrent C. difficile infections.


2019 ◽  
Vol 8 (6) ◽  
pp. 580-584
Author(s):  
Jillian M Cotter ◽  
Maribeth R Nicholson ◽  
Larry K Kociolek

Abstract Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Elvira Garza-González ◽  
Soraya Mendoza-Olazarán ◽  
Rayo Morfin-Otero ◽  
Andrea Ramírez-Fontes ◽  
Patricia Rodríguez-Zulueta ◽  
...  

Aim. In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI). Methods. We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing. Results. We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor’s pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041). Conclusion. Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3234
Author(s):  
Tanya M. Monaghan ◽  
Niharika A. Duggal ◽  
Elisa Rosati ◽  
Ruth Griffin ◽  
Jamie Hughes ◽  
...  

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.


Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 392
Author(s):  
Radek Sleha ◽  
Vera Radochova ◽  
Alexander Mikyska ◽  
Milan Houska ◽  
Radka Bolehovska ◽  
...  

Clostridioides (C.) difficile is an important causative pathogen of nosocomial gastrointestinal infections in humans with an increasing incidence, morbidity, and mortality. The available treatment options against this pathogen are limited. The standard antibiotics are expensive, can promote emerging resistance, and the recurrence rate of the infection is high. Therefore, there is an urgent need for new approaches to meet these challenges. One of the possible treatment alternatives is to use compounds available in commonly used plants. In this study, purified extracts isolated from hops—alpha and beta acids and xanthohumol—were tested in vivo for their inhibitory effect against C. difficile. A rat model of the peroral intestinal infection by C. difficile has been developed. The results show that both xanthohumol and beta acids from hops exert a notable antimicrobial effect in the C. difficile infection. The xanthohumol application showed the most pronounced antimicrobial effect together with an improvement of local inflammatory signs in the large intestine. Thus, the hops compounds represent promising antimicrobial agents for the treatment of intestinal infections caused by C. difficile.


2020 ◽  
Author(s):  
Daosheng Wang ◽  
Danfeng Dong ◽  
Chen Wang ◽  
Yingchao Cui ◽  
Cen Jiang ◽  
...  

Abstract Background: Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. Presently, we assessed the risk factors and intestinal microbiome of these patients to better understand the occurrence and development of CDI. Methods: Patients were screened for C. difficile every week after EN started and their clinical records were collected for risk factor identification. Feces were analyzed for 16S rRNA sequencing to evaluate the intestinal microbiota. Results : Overall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was associated with CDI occurrence (OR, 9.759; 95% CI, 2.140-44.498) and treatment with metronidazole could be protective (OR, 0.287; 95% CI, 0.091-0.902). Patients with EN had lower microbial richness and diversity, accompanied by reduced abundance of Bacteroides , Prevotella_9, Ruminococcaceae and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. At the initiation of EN, patients who were positive for C. difficile later had enhanced abundance of Bacteroides , which was negatively correlated with C. difficile load when CDI developed. Conclusion : ICU patients receiving EN had a high prevalence of CDI, and a fragile intestinal microbial environment. Alteration of microbiota composition could be vital in the process of CDI development, bringing new insights in the interaction between C. difficile and host microbiome.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures


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