Biology subjects

Phan, J. R.

Publications and source records attributed to Phan, J. R..

4 recordsLinked to original sources

bioRxiv2025

Effects of sexual dimorphism and estrous cycle on C. difficile infections prophylaxis in two rodent models

Clostridioides difficile infection (CDI) is responsible for the majority of identifiable hospital-related antibiotic-associated diarrhea. Susceptibility to CDI and severity of disease varies depending on a variety of factors such as aggressive use of broad-spectrum antibiotics, age, and immune status. Epidemiological studies have consistently shown that female patients are more at risk for CDI than their male counterparts. C. difficile is spread by spores which can persist in the environment and in the intestines of patients. Spores do not cause disease but germinate in the antibiotic-altered gut of patients to generate toxin producing vegetative cells. The germination of C. difficile spores is mediated by the composition of bile salts in the gut with taurocholate facilitating germination and chenodeoxycholate inhibiting it.

microbiology↗

bioRxiv2023

Effects of sexual dimorphism and estrous cycle on C. difficile infections in rodent models

Clostridioides difficile infection (CDI) is responsible for the majority of identifiable antibiotic-associated diarrhea. Women are more susceptible to CDI than men. In this study, we show that female mice developed more severe CDI than males. Furthermore, females in estrus developed only mild CDI 1-2 days later, while females in proestrus developed deadly disease. Mirroring the delayed effect of the estrous cycle, pre-infection prolactin levels formed a complex network with immunoglobulins and cytokines that affected early CDI severity one day after challenge. Similarly, pre-infection progesterone and luteinizing hormone formed a network that affected CDI two days after challenge. As expected, immune effectors early in the infection formed a hormone-independent network that concurrently correlated with CDI severity. Interestingly, early infection follicular stimulating hormone levels created a network that affected the CDI recovery phase. In summary, murine sexual hormones affect CDI progression by affecting the immune system both before and during disease progression.

microbiology↗

bioRxiv2021

A high-carbohydrate diet prolongs dysbiosis and Clostridioides difficile carriage and increases late-onset CDI and mortality in a hamster model of infection

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 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. 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 0% mortality in mice, 80% of hamsters fed the high-carbohydrate diet developed fulminant CDI and died, including several cases of late-onset CDI, whereas only 33% of hamsters fed a standard lab diet developed CDI only during the acute phase. We speculate that prolonged dysbiosis in these animals allowed C. difficile to proliferate following a three-day vancomycin course administered as part of this model system, leading to secondary CDI and eventual mortality. This study, along with similar studies in mouse models of CDI, suggests high-carbohydrate diets promote antibiotic-associated dysbiosis and long-term C. difficile carriage, which may convert to symptomatic CDI when conditions change. ImportanceThe effects of diet on CDI are not completely known, although most studies in mouse CDI models show that dietary carbohydrates ameliorate CDI. 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 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.

microbiology↗

bioRxiv2019

A high-fat/high-protein, Atkins-type diet exacerbates Clostridioides (Clostridium) difficile infection in mice, whereas a high-carbohydrate diet protects

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 high refined carbohydrate and low fiber content. 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 that is intensified by high-fat/high-protein diets; in contrast, high-carbohydrate diets might be protective regardless of the source of carbohydrate.

microbiology↗