Consumption of a Western-Style Diet Modulates the Response of the Murine Gut Microbiome to Ciprofloxacin

Abstract

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.

Coffee Consumption Modulates Amoxicillin-Induced Dysbiosis in the Murine Gut Microbiome

“…This indicates that compounds in coffee or caffeine alone do not significantly alter the overall microbiome composition (Figures 2A,B). As other studies have found, antibiotics led to significant changes in microbiome composition in mice, regardless of supplementation (Cabral D. et al, 2020;Cabral D. J. et al, 2019). Over the course of the experiment, our samples formed clusters mainly based on amoxicillin treatment (Figures 2C,D).…”

A Korean-Style Balanced Diet Has a Potential Connection with Ruminococcaceae Enterotype and Reduction of Metabolic Syndrome Incidence in Korean Adults

“…Finally, despite incompletely separated from ET-R, ET-B contained prevalent Bacteroidaceae in the family and Bilophila in the genus level. Previous studies have shown that Bacteroides enterotype has significant interaction with the Western-style diet [ 52 ], and persons with ET-B have consumed high animal protein and animal fat diets for long periods [ 29 , 53 ]. Bilophila tends to increase with the animal-based diet, which indicates Bilophila has a linkage with dietary fat intake [ 54 ].…”

Oxygen and Metabolism: Digesting Determinants of Antibiotic Susceptibility in the Gut

“…A disturbance of microbiome homeostasis (dysbiosis) is associated with various negative health consequences such as metabolic, developmental and immunological disorders that include inadequate nutrient and vitamin extraction, undernutrition, obesity, asthma, type 1 diabetes, and inflammatory bowel disease (IBD) ( Turnbaugh, 2006 ; Sekirov et al, 2008 ; Abrahamsson et al, 2014 ; Azad et al, 2014 ; Guarner and Malagelada 2003 ; Marchesi et al, 2007 ; Hsiao et al, 2013 ; Stefka et al, 2014 ; Lewis et al, 2015 ). The high prevalence of autoimmune disorders and allergies in developed nations has been partially attributed to altered or reduced colonization of symbionts in early childhood, possibly induced by factors such as higher rates of caesarean section, more time spent indoors, a low-fiber Western diet, and increased use of antibiotics ( Cabral et al, 2020 ; Rook and Brunet, 2005 , 2010 , 2012 , Rook et al, 2013 ; Kondrashova et al, 2013 ). Given the widespread use of antibiotics ( Shallcross and Davies 2014 ), it is essential to understand the mechanisms behind antibiotic-induced microbiota disturbances in order to further appreciate the dramatic effects that gut perturbation has on human health.…”

“…This is important because antibiotic-induced changes can generally be separated into two time frames: immediate drug-induced impacts and the long-term perturbations caused by disruptions in microbial and metabolic networks. A few studies have recently shown that short-term exposure to antibiotics induces dramatic changes to the microbiota within 12 hours ( Cabral et al, 2019 , Cabral et al, 2020 ), but additional work is needed to fully elucidate the immediate impact on microbial composition. Defining these rapid onset changes is key for determining the impact of location and metabolic environment on differential antibiotic susceptibility in the gut.…”

“…Recently, Cabral et al. demonstrated that consumption of a high-sugar/high-fat “Western”-style diet caused increased susceptibility to ciprofloxacin within the murine cecal microbiota ( Cabral et al, 2020 ). This work highlights the need for an expanded examination of dietary intake and antibiotic activity specifically regarding drug class, dietary composition, and induced-metabolic changes to multiple regions of the gut microbiome.…”