Trial Summary
What is the purpose of this trial?Recurrent Clostridioides difficle infection (rCDI) is a very significant problem in its own right and current fecal microbiota transplant (FMT) -based therapeutics will benefit from their optimization for this indication. It is likely that appropriate nutritional support coupled with microbiota-based drugs will yield superior clinical outcomes. However, both diet and gut microbiome are very complex. This project, which is based on a wealth of FMT experience, both clinical and investigational, over the past decade along with the novel techniques developed to identify dietary patterns and food groups that explain the most variation in gut microbiome, offers an ideal platform for performing systematic research in nutritional support that promotes gut microbiota health. The purpose is to Generate preliminary data with regards to tolerability of the Microbiota enhancing and nourishing diet (MEND) and its effects on the fecal microbiota in rCDI patients following FMT with the goal of developing larger clinical trials aimed to optimize post-FMT dietary management.
Is the treatment in the trial 'Specialized Diets for Clostridium Difficile Infection' a promising treatment?Yes, the treatment is promising. Research shows that a high-carbohydrate diet can protect against Clostridium difficile infection, while diets high in fat and protein can make the infection worse. Additionally, diets rich in microbiota-accessible carbohydrates, like those found in plants, can help reduce the infection by supporting beneficial gut bacteria.12456
What safety data exists for specialized diets in treating Clostridium difficile infection?The research indicates that high-fat/high-protein diets can exacerbate Clostridium difficile infection (CDI) in mice, leading to severe outcomes, while high-carbohydrate diets may offer protection. Additionally, microbiota-accessible carbohydrates (MACs) have been shown to suppress CDI in mice by promoting beneficial gut microbiota. These findings suggest that dietary interventions focusing on reducing fat and increasing carbohydrates, particularly MACs, could be beneficial in managing CDI. However, specific safety data for the MEND diet or similar specialized diets in humans is not directly addressed in the provided research.12456
What data supports the idea that Specialized Diets for Clostridium Difficile Infection is an effective treatment?The available research shows that dietary changes can impact Clostridium difficile infection (CDI). One study reported a successful case of treating CDI through dietary modification, suggesting that diet can play a role in managing the condition. Another study found that a high-carbohydrate diet protected mice from CDI, while high-fat/high-protein diets worsened the condition. However, in hamsters, a high-carbohydrate diet led to worse outcomes, indicating that the effectiveness of dietary treatments may vary across different models. Overall, these findings suggest that certain diets might help manage CDI, but more research is needed to understand their effects fully.13457
Do I have to stop taking my current medications for the trial?The trial protocol does not specify whether you need to stop taking your current medications. However, if you anticipate needing antibiotics during the study, you would be excluded from participating.
Eligibility Criteria
This trial is for adults at least 18 years old who have had two or more recurrences of Clostridium difficile infection within a year and are planning to undergo fecal microbiota transplant (FMT) therapy. Participants must be able to follow the study requirements and give informed consent.Treatment Details
The trial is testing two diets, MEND and mNICE, designed to optimize gut health after FMT in patients with recurrent C. difficile infections. The goal is to see how well these diets support recovery by nourishing the new microbiome established by FMT.
2Treatment groups
Experimental Treatment
Active Control
Group I: MEND dietExperimental Treatment1 Intervention
patients being treated with FMT
Group II: mNICE (modified NICE) dietActive Control1 Intervention
patients being treated with FMT
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of MinnesotaMinneapolis, MN
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Who is running the clinical trial?
University of MinnesotaLead Sponsor
References
Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol. [2020]To determine the therapeutic effects of dietary supplementation on Clostridium difficile infection (CDI).
Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model. [2021]Clostridium difficile is an opportunistic diarrhoeal pathogen, and C. difficile infection (CDI) represents a major health care concern, causing an estimated 15,000 deaths per year in the United States alone 1 . Several enteric pathogens, including C. difficile, leverage inflammation and the accompanying microbial dysbiosis to thrive in the distal gut 2 . Although diet is among the most powerful available tools for affecting the health of humans and their relationship with their microbiota, investigation into the effects of diet on CDI has been limited. Here, we show in mice that the consumption of microbiota-accessible carbohydrates (MACs) found in dietary plant polysaccharides has a significant effect on CDI. Specifically, using a model of antibiotic-induced CDI that typically resolves within 12 days of infection, we demonstrate that MAC-deficient diets perpetuate CDI. We show that C. difficile burdens are suppressed through the addition of either a diet containing a complex mixture of MACs or a simplified diet containing inulin as the sole MAC source. We show that switches between these dietary conditions are coincident with changes to microbiota membership, its metabolic output and C. difficile-mediated inflammation. Together, our data demonstrate the outgrowth of MAC-utilizing taxa and the associated end products of MAC metabolism, namely, the short-chain fatty acids acetate, propionate and butyrate, are associated with decreased C. difficile fitness despite increased C. difficile toxin expression in the gut. Our findings, when placed into the context of the known fibre deficiencies of a human Western diet, provide rationale for pursuing MAC-centric dietary strategies as an alternate line of investigation for mitigating CDI.
Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection. [2020]Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal microbiota transplantation from donors with a normal microbiota effectively treats C. difficile infection.
Dietary therapy for clostridium difficile colonization: A case series. [2020]Clostridium difficile (C. difficile) is an important nosocomial pathogen in adults and children. Roughly 4-5% of non hospitalized healthy adults carry the organism in their intestinal flora while adults in long term care facilities have asymptomatic carriage rates estimated at 20-50%. C. difficile colonization results in a spectrum of clinical conditions from asymptomatic carrier state to fulminant colitis. Changes in the fecal microbiome are central in the development of C. difficile colonization and disease pathogenesis. C. difficile infection has been shown to be associated with reduced biodiversity of the gut microbiome and intestinal dysbiosis. With the importance of the intestinal microbiota in development of CDI and with the known impact of diet on the intestinal microbiota, we report the first known case of C. difficile colonization/recurrence successful treated by dietary modification.
A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides (Clostridium) difficile Infection in Mice, whereas a High-Carbohydrate Diet Protects. [2021]Clostridioides difficile (formerly Clostridium difficile) infection (CDI) can result from the disruption of the resident gut microbiota. Western diets and popular weight-loss diets drive large changes in the gut microbiome; however, the literature is conflicted with regard to the effect of diet on CDI. Using the hypervirulent strain C. difficile R20291 (RT027) in a mouse model of antibiotic-induced CDI, we assessed disease outcome and microbial community dynamics in mice fed two high-fat diets in comparison with a high-carbohydrate diet and a standard rodent diet. The two high-fat diets exacerbated CDI, with a high-fat/high-protein, Atkins-like diet leading to severe CDI and 100% mortality and a high-fat/low-protein, medium-chain-triglyceride (MCT)-like diet inducing highly variable CDI outcomes. In contrast, mice fed a high-carbohydrate diet were protected from CDI, despite the high levels of refined carbohydrate and low levels of fiber in the diet. A total of 28 members of the Lachnospiraceae and Ruminococcaceae decreased in abundance due to diet and/or antibiotic treatment; these organisms may compete with C. difficile for amino acids and protect healthy animals from CDI in the absence of antibiotics. Together, these data suggest that antibiotic treatment might lead to loss of C. difficile competitors and create a favorable environment for C. difficile proliferation and virulence with effects that are intensified by high-fat/high-protein diets; in contrast, high-carbohydrate diets might be protective regardless of the source of carbohydrate or of antibiotic-driven loss of C. difficile competitors.IMPORTANCE The role of Western and weight-loss diets with extreme macronutrient composition in the risk and progression of CDI is poorly understood. In a longitudinal study, we showed that a high-fat/high-protein, Atkins-type diet greatly exacerbated antibiotic-induced CDI, whereas a high-carbohydrate diet protected, despite the high monosaccharide and starch content. Our study results, therefore, suggest that popular high-fat/high-protein weight-loss diets may enhance CDI risk during antibiotic treatment, possibly due to the synergistic effects of a loss of the microorganisms that normally inhibit C. difficile overgrowth and an abundance of amino acids that promote C. difficile overgrowth. In contrast, a high-carbohydrate diet might be protective, despite reports on the recent evolution of enhanced carbohydrate metabolism in C. difficile.
Dietary fat promotes antibiotic-induced Clostridioides difficile mortality in mice. [2022]Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea, and emerging evidence has linked dietary components with CDI pathogenesis, suggesting that dietary modulation may be an effective strategy for prevention. Here, we show that mice fed a high-fat/low-fiber "Western-type" diet (WD) had dramatically increased mortality in a murine model of antibiotic-induced CDI compared to a low-fat/low-fiber (LF/LF) diet and standard mouse chow controls. We found that the WD had a pro- C. difficile bile acid composition that was driven in part by higher levels of primary bile acids that are produced to digest fat, and a lower level of secondary bile acids that are produced by the gut microbiome. This lack of secondary bile acids was associated with a greater disturbance to the gut microbiome with antibiotics in both the WD and LF/LF diet compared to mouse chow. Mice fed the WD also had the highest level of toxin TcdA just prior to the onset of mortality, but not of TcdB or increased inflammation. These findings indicate that dietary intervention to decrease fat may complement previously proposed dietary intervention strategies to prevent CDI in high-risk individuals.
A High-Carbohydrate Diet Prolongs Dysbiosis and Clostridioides difficile Carriage and Increases Delayed Mortality in a Hamster Model of Infection. [2023]Studies using mouse models of Clostridioides difficile infection (CDI) have demonstrated a variety of relationships between dietary macronutrients on antibiotic-associated CDI; however, few of these effects have been examined in more susceptible hamster models of CDI. In this study, we investigated the effect of a high-carbohydrate diet previously shown to protect mice from CDI on the progression and resolution of CDI in a hamster disease model, with 10 animals per group. Hamsters fed the high-carbohydrate diet developed distinct diet-specific microbiomes during antibiotic treatment and CDI, with lower diversity, persistent C. difficile carriage, and delayed microbiome restoration. In contrast to CDI protection in mice, most hamsters fed a high-carbohydrate diet developed fulminant CDI including several cases of late-onset CDI, that were not observed in hamsters fed a standard lab diet. We speculate that prolonged high-carbohydrate diet-specific dysbiosis in these animals allowed C. difficile to persist in the gut of the animals where they could proliferate postvancomycin treatment, leading to delayed CDI onset. This study, along with similar studies in mouse models of CDI, suggests some high-carbohydrate diets may promote antibiotic-associated dysbiosis and long-term C. difficile carriage, which may later convert to symptomatic CDI. IMPORTANCE The effects of diet on CDI are not completely known. Here, we used a high-carbohydrate diet previously shown to protect mice against CDI to assess its effect on a hamster model of CDI and paradoxically found that it promoted dysbiosis, C. difficile carriage, and higher mortality. A common thread in both mouse and hamster experimental models was that the high-carbohydrate diet promoted dysbiosis and long-term carriage of C. difficile, which may have converted to fulminant CDI only in the highly susceptible hamster model system. If diets high in carbohydrates also promote dysbiosis and C. difficile carriage in humans, then these diets might paradoxically increase chances of CDI relapse despite their protective effects against primary CDI.