PT  - JOURNAL ARTICLE
AU  - Damien J. Cabral
AU  - Jenna I. Wurster
AU  - Benjamin J. Korry
AU  - Swathi Penumutchu
AU  - Peter Belenky
TI  - Consumption of a Western-style diet modulates the response of the murine gut microbiome to ciprofloxacin
AID  - 10.1101/780049
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 780049
4099  - http://biorxiv.org/content/early/2019/09/24/780049.short
4100  - http://biorxiv.org/content/early/2019/09/24/780049.full
AB  - Background Dietary composition and antibiotic use are known to have major impacts on the structure and function of the gut microbiome. In turn, the dysbiosis caused by antibiotic treatment or consumption of diets low in microbiota-accessible carbohydrates (MACs) is associated with a number of acute or chronic co-morbities in the host, such as obesity or opportunistic infections. Despite this, little research has been done to explore the role of host diet as a determinant of antibiotic-induced microbiome disruption.Results Here, we utilize a multi-omic approach to characterize the impact of Western-style diet consumption on ciprofloxacin-induced changes to gut microbiome community structure and transcriptional activity. We found that mice consuming a Western-style diet experienced a greater expansion of Firmicutes following ciprofloxacin treatment than those eating a control diet. At the transcriptional level, we found that ciprofloxacin induced a reduction in the abundance of 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 shared response, we observed extensive differences in the response of the microbiota to ciprofloxacin on each diet. 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.Conclusions Our findings build on recent work and demonstrates that host diet plays a key role in determining the extent of microbiome disruption induced by antibiotic treatment. Thus, future studies investigating the impact of antibiotics on the microbiota should consider the impact that dietary composition may have on the interpretation of results. In the long term, the relationship between diet and microbiome disruption may help to identify ways to reduce the incidence of dysbiosis following clinical therapy in humans.