Updating changes in human gut microbial communities associated with Clostridioides difficile infection.

Clostridioides difficile is the causative agent of antibiotic-associated diarrhea, a worldwide public health problem. Different factors can promote the progression of C. difficile infection (CDI), mainly altered intestinal microbiota composition. Microbial species belonging to different domains (i.e., bacteria, archaea, eukaryotes, and even viruses) are synergistically and antagonistically associated with CDI. This review was aimed at updating changes regarding CDI-related human microbiota composition using recent data and an integral approach that included the different microorganism domains. The three domains of life contribute to intestinal microbiota homeostasis at different levels in which relationships among microorganisms could explain the wide range of clinical manifestations. A holistic understanding of intestinal ecosystem functioning will facilitate identifying new predictive factors for infection and developing better treatment and new diagnostic tools, thereby reducing this disease's morbidity and mortality.

Protection from Lethal Clostridioides difficile Infection via Intraspecies Competition for Cogerminant.

Clostridioides difficile, a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor for C. difficile infection (CDI), as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetative C. difficile To date, the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is nontoxigenic C. difficile Using multiple infection models, we determined that precolonization with a less virulent strain is sufficient to protect from challenge with a lethal strain of C. difficile, surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain. Our results suggest that reduction of amino acids, specifically glycine following colonization by the first strain of C. difficile, is sufficient to decrease germination of the second strain, thereby limiting colonization by the lethal strain.IMPORTANCE Antibiotic-associated colitis is often caused by infection with the bacterium Clostridioides difficile In this study, we found that reduction of the amino acid glycine by precolonization with a less virulent strain of C. difficile is sufficient to decrease germination of a second strain. This finding demonstrates that the axis of competition for nutrients can include multiple life stages. This work is important, as it is the first to identify a possible mechanism through which precolonization with C. difficile, a current clinical therapy, provides protection from reinfection. Furthermore, our work suggests that targeting nutrients utilized by all life stages could be an improved strategy for bacterial therapeutics that aim to restore colonization resistance in the gut.

In Vitro Investigation of Auranofin as a Treatment for Clostridium difficile Infection.

BACKGROUND: Clostridium difficile infection is the leading cause of hospital-acquired gastrointestinal infection and incidence rates continue to rise. Clostridium difficile infection is becoming increasingly complex to treat owing to the rise in treatment failures and recurrent infections. There is a clear need for new therapeutic options for the management of this disease. OBJECTIVE: This study aimed to assess auranofin, a drug approved for the treatment of arthritis, as a treatment for C. difficile infection. Previous investigations have demonstrated potential antimicrobial activity of auranofin against C. difficile and other organisms. METHODS: The activity of auranofin was assessed by in vitro investigations of its effect on C. difficile M7404 growth, vegetative cell viability, and spore viability. Activity of auranofin was also compared to that of the current treatments, metronidazole and vancomycin. RESULTS: Auranofin showed bactericidal activity at concentrations as low as 4.07 µg/mL, effectively reducing bacterial cell density by 50-70% and the viable vegetative cell and spore yields by 100%. The activity of auranofin was shown to be non-inferior to that of metronidazole and vancomycin. CONCLUSIONS: Auranofin is highly efficacious against C. difficile M7404 in vitro and has the potential to be an ideal therapeutic option for the treatment of C. difficile infection.

Bacteria producing antimicrobials against Clostridium difficile isolated from human stool.

Clostridium difficile infection (CDI) is a common cause of morbidity and mortality in hospitalized patients worldwide. The major problem facing current treatment is multiple recurrences, prompting the need for alternative therapies. In this study we isolated bacterial species, from Egyptian individuals' stool, with antimicrobial activity against clinical isolates of C. difficile and tried to examine the nature of the produced antimicrobials. In vitro antibacterial activity against C. difficile was initially screened in 123 fecal samples cultures using an agar overlay method. The isolates with antimicrobial activity against C. difficile in addition to Clostridium isolates were identified using partial 16S rDNA gene sequencing analysis. The isolates acting against C. difficile belonged to Lactobacillus, Enterococcus and Clostridium genera. The concentrated cell-free supernatants (CFSs) from these bacterial isolates were examined for antimicrobial activity against C. difficile growth by broth dilution method. 10 x concentrated CFSs of five isolates showed inhibition for C. difficile growth which was significantly different (p < 0.001) from control. Lactobacillus agilis T99A and Clostridium butyricum T58A isolates were selected for further evaluation of the produced antimicrobials. The antimicrobial activity of 10x CFSs of the two isolates was stable after enzymatic treatment with proteinase K or heating treatments up to 90 °C or neutralizing pH. The spectrum of activity of the two isolates was evaluated using different gram-positive and gram-negative bacterial species and did not show antimicrobial activity against these species. Our results showed two unconventional bacterial isolates: L. agilis T99A and C. butyricum T58A producing extracellular thermo stable antimicrobial agents against C. difficile clinical isolates.

The emergence of metronidazole and vancomycin reduced susceptibility in Clostridium difficile isolates in Iran.

OBJECTIVES: Clostridium difficile (C. difficile) is the main causative agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis. The accumulation of antimicrobial resistance in C. difficile strains can drive C. difficile infection (CDI) epidemiology. This study was undertaken to evaluate the antimicrobial resistance patterns of toxigenic C. difficile isolates cultured from diarrhoeal stool samples of hospitalised patients with suspected CDI in three tertiary care hospitals in Tehran, Iran. METHODS: Two hundred and fifty diarrhoeal stool samples were investigated by toxigenic culture using cycloserine-cefoxitin-fructose agar and the VERO cell line. Antimicrobial susceptibility to metronidazole, vancomycin, clindamycin, tetracycline, and moxifloxacin was performed by disk diffusion and Etest methods on Brucella Blood Agar supplemented with hemin and vitamin K. RESULTS: Thirty-five stool samples (14.0%) proved positive using C. difficile toxigenic culture. According to Clinical and Laboratory Standards Institute breakpoints, the following resistance was identified in C. difficile isolates: metronidazole (2 of 35); moxifloxacin (7 of 35); clindamycin (18 of 35); and tetracycline (5 of 35). Using European Committee on Antimicrobial Susceptibility Testing breakpoints, three of 35 isolates showed reduced-susceptibility for vancomycin and 14 of 35 for metronidazole. In addition, the results showed a good correlation between the inhibition zone diameter (disk diffusion) and MIC values (Etest); Pearson correlation coefficient 0.7400.95 (P< 0.001). CONCLUSIONS: Multidrug resistance was observed in Iranian clinical toxigenic C. difficile isolates, including reduced susceptibility to first-line CDI treatment drugs. In addition, disk diffusion can be used as a cost-effective option for the antimicrobial susceptibility testing of C. difficile isolates.

Effect of antibiotic treatment on the formation of non-spore Clostridium difficile persister-like cells.

Background: The spore is the virulence factor identified to be involved in the recurrence of the disease caused by Clostridium difficile. Objectives: To demonstrate that lethal antibiotic concentrations induce the appearance of C. difficile persister-like non-spore cells. Methods: C. difficile and derivative spo0A mutant strains were tested for their susceptibility to antibiotics, as determined using an agar dilution method. Persister-cell generation was determined for all strains using up to 10â€Š× the MIC of every antibiotic for up to 6 days. Results: Using up to 10â€Š× the MIC of every antibiotic, we were able to induce the appearance of persister-like behaviour since biphasic killing curves could be observed in response to treatment antibiotics. Conclusions: To the best of our knowledge, this work provides, for the first time, experimental evidence of the appearance of C. difficile persister-like cells, opening a new research avenue in the pathogenesis of this nosocomial pathogen.

Faecalibacterium prausnitzii and a Prebiotic Protect Intestinal Health in a Mouse Model of Antibiotic and Clostridium difficile Exposure.

BACKGROUND: Clostridium difficile (CD) infection (CDI) increases patient morbidity, mortality and healthcare costs. Antibiotic treatment induces gut dysbiosis and is both a major risk factor for CD colonization and treatment of CDI. Probiotics have been trialed to support commensal gut microbiota and reduce CDI. This study investigated commensal microbe Faecalibacterium prausnitzii (FP) and a prebiotic, both known to yield butyrate and be anti-inflammatory and immunomodulatory, on CD colonization and gut integrity in mice. METHODS: Mice were randomly grouped and supplemented daily with FP, prebiotic, FP + prebiotic, FP/prebiotic supernatant, or saline throughout the entire study. Following treatment with clindamycin for 3 days, mice were exposed to CD. Feces were collected at baseline, the day after antibiotic, and 1, 3, and 5 days after CD exposure and cultured for bacterial overgrowth and CD colonization. On days 1 and 5 after CD exposure, mice were randomly euthanized, and proximal colon was dissected for histological analysis and preparation of RNA for analysis of proinflammatory and anti-inflammatory cytokines. RESULTS: Although all mice exhibited bacterial overgrowth and CD colonization, bacterial burden resolved quicker in the FP + prebiotic group. This was associated with induction and resolution of innate immune responses, anion exchanger, and tight junction protein preservation in proximal colon. CD toxin virulence potential was questionable as expression of CD toxin B receptor was depleted in the FP + prebiotic group. CONCLUSION: Supplementation with anti-inflammatory butyrate-supporting commensal bacteria and prebiotic may support innate immune responses and minimize bacterial burden and negative effects during antibiotic and CD exposure.

High prevalence of Clostridium difficile on retail root vegetables, Western Australia.

AIMS: The incidence of community-associated Clostridium difficile infection (CA-CDI) in Australia has increased since mid-2011. With reports of clinically important C. difficile strains being isolated from retail foods in Europe and North America, a foodborne source of C. difficile in cases of CA-CDI is a possibility. This study represents the first to investigate the prevalence and genotypes of C. difficile in Australian retail vegetables. METHODS AND RESULTS: A total of 300 root vegetables grown in Western Australia (WA) were collected from retail stores and farmers' markets. Three vegetables of the same kind bought from the same store/market were treated as one sample. Selective enrichment culture, toxin profiling and PCR ribotyping were performed. Clostridium difficile was isolated from 30% (30/100) of pooled vegetable samples, 55·6% of organic potatoes, 50% of nonorganic potatoes, 22·2% of organic beetroots, 5·6% of organic onions and 5·3% of organic carrots. Over half (51·2%, 22/43) the isolates were toxigenic. Many of the ribotypes of C. difficile isolated were common among human and Australian animals. CONCLUSIONS: Clostridium difficile could be found commonly on retail root vegetables of WA. This may be potential sources for CA-CDI. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enhances knowledge of possible sources of C. difficile in the Australian community, outside the hospital setting.

Analysis of Clostridium difficile biofilms: imaging and antimicrobial treatment.

BACKGROUND: Clostridium difficile, a spore-forming Gram-positive anaerobic bacillus, is the most common causative agent of healthcare-associated diarrhoea. Formation of biofilms may protect C. difficile against antibiotics, potentially leading to treatment failure. Furthermore, bacterial spores or vegetative cells may linger in biofilms in the gut causing C. difficile infection recurrence. OBJECTIVES: In this study, we evaluated and compared the efficacy of four antibiotics (fidaxomicin, surotomycin, vancomycin and metronidazole) in penetrating C. difficile biofilms and killing vegetative cells. METHODS: C. difficile biofilms grown initially for 48 or 72 h using the colony biofilm model were then treated with antibiotics at a concentration of 25 × MIC for 24 h. Vegetative cells and spores were enumerated. The effect of treatment on biofilm structure was studied by scanning electron microscopy (SEM). The ability of fidaxomicin and surotomycin to penetrate biofilms was studied using fluorescently tagged antibiotics. RESULTS: Both surotomycin and fidaxomicin were significantly more effective than vancomycin or metronidazole (P < 0.001) at killing vegetative cells in established biofilms. Fidaxomicin was more effective than metronidazole at reducing viable spore counts in biofilms (P < 0.05). Fluorescently labelled surotomycin and fidaxomicin penetrated C. difficile biofilms in < 1 h. After 24 h of treatment, SEM demonstrated that both fidaxomicin and surotomycin disrupted the biofilm structure, while metronidazole had no observable effect. CONCLUSIONS: Fidaxomicin is effective in disrupting C. difficile biofilms, killing vegetative cells and decreasing spore counts.

Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria.

Anaerobic bacteria, such as Bacteroides fragilis or Clostridium perfringens, are part of indigenous human flora. However, Clostridium difficile represents also an important causative agent of nosocomial infectious antibiotic-associated diarrhoea. Treatment of C. difficile infection is problematic, making it imperative to search for new compounds with antimicrobial properties. Hops (Humulus lupulus L.) contain substances with antibacterial properties. We tested antimicrobial activity of purified hop constituents humulone, lupulone and xanthohumol against anaerobic bacteria. The antimicrobial activity was established against B. fragilis, C. perfringens and C. difficile strains according to standard testing protocols (CLSI, EUCAST), and the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were calculated. All C. difficile strains were toxigenic and clinically relevant, as they were isolated from patients with diarrhoea. Strongest antimicrobial effects were observed with xanthohumol showing MIC and MBC values of 15-107 µg/mL, which are close to those of conventional antibiotics in the strains of bacteria with increased resistance. Slightly higher MIC and MBC values were obtained with lupulone followed by higher values of humulone. Our study, thus, shows a potential of purified hop compounds, especially xanthohumol, as alternatives for treatment of infections caused by select anaerobic bacteria, namely nosocomial diarrhoea caused by resistant strains.

An in silico evaluation of treatment regimens for recurrent Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is a significant nosocomial infection worldwide, that recurs in as many as 35% of infections. Risk of CDI recurrence varies by ribotype, which also vary in sporulation and germination rates. Whether sporulation/germination mediate risk of recurrence and effectiveness of treatment of recurring CDI remains unclear. We aim to assess the role of sporulation/germination patterns on risk of recurrence, and the relative effectiveness of the recommended tapered/pulsing regimens using an in silico model. METHODS: We created a compartmental in-host mathematical model of CDI, composed of vegetative cells, toxins, and spores, to explore whether sporulation and germination have an impact on recurrence rates. We also simulated the effectiveness of three tapered/pulsed vancomycin regimens by ribotype. RESULTS: Simulations underscored the importance of sporulation/germination patterns in determining pathogenicity and transmission. All recommended regimens for recurring CDI tested were effective in reducing risk of an additional recurrence. Most modified regimens were still effective even after reducing the duration or dosage of vancomycin. However, the effectiveness of treatment varied by ribotype. CONCLUSION: Current CDI vancomycin regimen for treating recurrent cases should be studied further to better balance associated risks and benefits.

In vitro and in vivo antagonistic activity of new probiotic culture against Clostridium difficile and Clostridium perfringens.

BACKGROUND: Genus Clostridium accompanies more than 200 known species and at least 30 among them are associated with human and animal diseases. At the moment, the treatment of clostridial infections is based on use of antibiotics. However, due to the European ban on the use of antibiotics in livestock production, novel therapeutic strategies for treatment of these hardly curable infections have been evaluated. Hence, in this study the antimicrobial effect of newly designed probiotic culture consisted of natural isolates Lactobacillus helveticus BGRA43, Lactobacillus fermentum BGHI14 and Streptococcus thermophilus BGVLJ1-44 against Clostridium difficile and Clostridium perfringens was analyzed. RESULTS: The probiotic culture showed strong in vitro antimicrobial effect on C. difficile (human clinical isolate). In addition, individual strains and the probiotic combination exhibited immunomodulatory activity. The probiotic combination significantly increased the proliferation of GALT lymphocytes. At the other hand, none of the bacterial treatments (individual strains and the combination) induced the production of proinflammatory cytokines IL-6 and IL-1ß by intestinal epithelial cells, Caco-2. Interestingly, Caco-2 cells exposed to the probiotic combination produced significantly elevated amount of TGFß pointing to potential protecting effect of the probiotic. In addition, the results of field trial on spontaneously infected goats revealed reduction of C. perfringens in goats (below the detection threshold) after the probiotic treatment. CONCLUSIONS: The results of this study indicated that the novel probiotic deserves to be further investigated as a promising antimicrobial agent against C. difficile and C. perfringens.

A human gut ecosystem protects against C. difficile disease by targeting TcdA.

BACKGROUND: A defined Microbial Ecosystem Therapeutic (MET-1, or "RePOOPulate") derived from the feces of a healthy volunteer can cure recurrent C. difficile infection (rCDI) in humans. The mechanisms of action whereby healthy microbiota protect against rCDI remain unclear. Since C. difficile toxins are largely responsible for the disease pathology of CDI, we hypothesized that MET-1 exerts its protective effects by inhibiting the effects of these toxins on the host. METHODS: A combination of in vivo (antibiotic-associated mouse model of C. difficile colitis, mouse ileal loop model) and in vitro models (FITC-phalloidin staining, F actin Western blots and apoptosis assay in Caco2 cells, transepithelial electrical resistance measurements in T84 cells) were employed. RESULTS: MET-1 decreased both local and systemic inflammation in infection and decreased both the cytotoxicity and the amount of TcdA detected in stool, without an effect on C. difficile viability. MET-1 protected against TcdA-mediated damage in a murine ileal loop model. MET-1 protected the integrity of the cytoskeleton in cells treated with purified TcdA, as indicated by FITC-phalloidin staining, F:G actin assays and preservation of transepithelial electrical resistance. Finally, co-incubation of MET-1 with purified TcdA resulted in decreased detectable TcdA by Western blot analysis. CONCLUSIONS: MET-1 intestinal microbiota confers protection against C. difficile and decreases C. difficile-mediated inflammation through its protective effects against C. difficile toxins, including enhancement of host barrier function and degradation of TcdA. The effect of MET-1 on C. difficile viability seems to offer little, if any, contribution to its protective effects on the host.

A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection.

BACKGROUND: Patients with recurrent Clostridium difficile infection (CDI) have a ≥60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. METHODS: Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 × 10(9) spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 10(8) spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. RESULTS: Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. CONCLUSIONS: SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.

Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI), but its mechanisms remain poorly understood. Emerging evidence suggests that gut bile acids have significant influence on the physiology of C. difficile, and therefore on patient susceptibility to recurrent infection. We analyzed spore germination of 10 clinical C. difficile isolates exposed to combinations of bile acids present in patient feces before and after FMT. Bile acids at concentrations found in patients' feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains. Sequencing of the newly identified germinant receptor in C. difficile, CspC, revealed a possible correspondence of variation in germination responses across isolates with mutations in this receptor. This may be related to interstrain variability in spore germination and vegetative growth in response to bile acids seen in this and other studies. These results support the idea that intra-colonic bile acids play a key mechanistic role in the success of FMT, and suggests that novel therapeutic alternatives for treatment of R-CDI may be developed by targeted manipulation of bile acid composition in the colon.

Persistence of Clostridium difficile in wastewater treatment-derived biosolids during land application or windrow composting.

AIMS: To determine the persistence of Clostridium difficile spores in biosolids during composting or when amended into soil and held under natural environmental climatic conditions. METHODS AND RESULTS: Five log CFU g(-1) Cl. difficile spores (ribotypes 027 or 078) were inoculated into agricultural soils (sandy loam or loam) amended with 10% w/w anaerobically digested biosolids. The inoculated soil : biosolids mixture was then placed into sentinel vials which were introduced at a depth of 15 cm within the field plot consisting of the corresponding soil type. Two trials were performed, the first of which started in late spring (May 2013 through to August 2014) and second from November 2013 through to October 2014 (fall trial). Ribotype 078 endospores in loam or sandy loam soil decreased during the summer but then increased in numbers towards the fall. At the end of the trial, levels of ribotype 078 spores had decreased by 1·5 log CFU g(-1) , with 027 spores decreasing by <1 log CFU g(-1) over the same time period. Windrow composting of biosolids decreased Cl. difficile levels from 3·7 log CFU g(-1) down to 0·3 log CFU g(-1) with the greater reduction occurring during the curing phase. In comparison, Cl. perfringens decreased from 6·3 log CFU g(-1) down to 2·4 log CFU g(-1) but mainly in the thermal phase of the composting process. CONCLUSIONS: Composting of biosolids is a more effective means of inactivating Cl. difficile compared to land application. SIGNIFICANCE AND IMPACT OF THE STUDY: Windrow composting represents an effective method to reduce the environmental burden of Cl. difficile associated with biosolids.

Inhibitory Effect of Epigallocatechin Gallate on the Virulence of Clostridium difficile PCR Ribotype 027.

Clostridium difficile infection (CDI) is the most prevalent cause of health-care-associated infections. CDI-related health-care costs and deaths are both increasing annually on a global scale. C. difficile have been reported in food products in Canada, Europe, and the United States; however, the systematic transmission of C. difficile between humans and animals is yet to be understood. Because of the limitations of current therapeutic options, there is a need for the development of new patient treatments. Epigallocatechin gallate (EGCG) is a major catechin compound found in green tea extracts and exhibits antioxidant and antimicrobial activities. This study was conducted to investigate the inhibitory effects of EGCG on the expression of virulence genes in C. difficile and in C. difficile-associated diseases by inhibition of quorum sensing. The protein expression of autoinducer-2 (AI-2) was evaluated by AI-2 activity. EGCG at various concentrations had an inhibitory effect on AI-2 production, especially at 10 µg/mL. EGCG also significantly repressed the transcription of virulence genes, including luxS and tcdA, and prolonged the survival of Caenorhabditis elegans infected with C. difficile. Furthermore, treatment with EGCG effectively protected C. difficile-infected mice from C. difficile-induced death. Histological analysis of the colon and cecum of these mice revealed that EGCG protected tissues of the lower intestinal tract from damage. EGCG exerted growth-inhibitory and bactericidal activities on C. difficile in C. difficile-infected mice. Our results suggest that EGCG has significant antipathogenic effects on C. difficile and can be used to prevent or treat C. difficile-associated diseases or C. difficile infections.

Antibiotic overuse and Clostridium difficile infections: the Indian paradox and the possible role of dietary practices.

Antibiotic abuse is rampant in India, such that one may expect to see an increase of Clostridium difficile infections (CDI). However, we found that the incidence of CDI in India (1.67%) is no different from that reported in USA (1.6%) using similar techniques of detection (polymerase chain reaction test). We offer a possible explanation for this paradox. It is likely that a diet rich in fiber, yogurt, and possibly turmeric may have a protective role in decreasing the incidence of CDIs in India.

Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome.

Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.