Highlights d Antibiotics perturb the metabolic capacity of the murine gut microbiome d Amoxicillin elevates expression of starch utilization genes in B. thetaiotaomicron d Fiber supplementation protects B. thetaiotaomicron from amoxicillin in vitro d Host diet has a major effect on the response of the microbiome to amoxicillin

Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. However, severe C. albicans infections are relatively rare, occurring mostly in the very young, the very old, and immunocompromised individuals. The fact that these infections are rare is interesting because as much as 80 percent of the population is asymptomatically colonized with C. albicans. It is thought that members of the human microbiota and the immune system work in concert to reduce C. albicans overgrowth through competition and modification of the growth environment. Here, we report that Escherichia coli (strain MG1655) outcompetes and kills C. albicans (strain SC5314) in vitro. We find that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.

Dietary composition and antibiotic use have major impacts on the structure and function of the gut microbiome, often resulting in dysbiosis. Despite this, little research has been done to explore the role of host diet as a determinant of antibiotic-induced microbiome disruption. Here, we utilize a multi-omic approach to characterize the impact of Western-style diet consumption on ciprofloxacin-induced changes to gut microbiome structure and transcriptional activity. We found that Western diet consumption dramatically increased Bacteroides abundances and shifted the community toward the metabolism of simple sugars and mucus glycoproteins. Mice consuming a Western-style diet experienced a greater expansion of Firmicutes following ciprofloxacin treatment than those eating a control diet. Transcriptionally, we found that ciprofloxacin reduced the abundance of tricarboxylic acid (TCA) cycle transcripts on both diets, suggesting that carbon metabolism plays a key role in the response of the gut microbiome to this antibiotic. Despite this, we observed extensive diet-dependent differences in the impact of ciprofloxacin on microbiota function. In particular, at the whole-community level we detected an increase in starch degradation, glycolysis, and pyruvate fermentation following antibiotic treatment in mice on the Western diet, which we did not observe in mice on the control diet. Similarly, we observed diet-specific changes in the transcriptional activity of two important commensal bacteria, Akkermansia muciniphila and Bacteroides thetaiotaomicron, involving diverse cellular processes such as nutrient acquisition, stress responses, and capsular polysaccharide (CPS) biosynthesis. These findings demonstrate that host diet plays a role in determining the impacts of ciprofloxacin on microbiome composition and microbiome function. IMPORTANCE Due to the growing incidence of disorders related to antibiotic-induced dysbiosis, it is essential to determine how our “Western”-style diet impacts the response of the microbiome to antibiotics. While diet and antibiotics have profound impacts on gut microbiome composition, little work has been done to examine their combined effects. Previous work has shown that nutrient availability, influenced by diet, plays an important role in determining the extent of antibiotic-induced disruption to the gut microbiome. Thus, we hypothesize that the Western diet will shift microbiota metabolism toward simple sugar and mucus degradation and away from polysaccharide utilization. Because of bacterial metabolism’s critical role in antibiotic susceptibility, this change in baseline metabolism will impact how the structure and function of the microbiome are impacted by ciprofloxacin exposure. Understanding how diet modulates antibiotic-induced microbiome disruption will allow for the development of dietary interventions that can alleviate many of the microbiome-dependent complications of antibiotic treatment.