Prebiotics Modulate the Effects of Antibiotics on Gut Microbial Diversity and Functioning in Vitro

Abstract

Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation--another method used to modulate gut composition and function--could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota.

Keywords: antibiotics; fibre; gut microbiota; prebiotics.

Figure 1

(A) The first two principal components representing variation in frequencies of common genera across Human Microbiome Project samples (grey), stool samples from Stearns et al. [35] (also grey), colon samples from Stearns et al. [35] (blue), our starting cultures (marked by +) and our time 10 experimental samples (orange). Correlations with six main genera are shown. (B) An expanded plot focusing on our experimental samples, with arrows showing the change in mean values of principal component 1 (PC1) and principal component 2 (PC2) in each experimental treatment. Faecalibacterium (Faec), Clostridium (Closr), Roseburia (Rose), Bacteroides (Bac), Parabacteroides (Para).

Figure 2

Changes in the abundance of total bacteria (A) to (C), Bacteroides (D) to (F) and Bifidobacterium (G) to (I) as determined by FISH counts during the course of the experiment. Columns show results with no antibiotics ((A, D, G), solid lines), gentamicin ((B, E, H), dashed lines) and ampicillin ((C, F, I), dotted lines) in turn. Standard error bars are shown. Black = control; green = inulin; red = pectin. Total (total bacterial abundance), Bacteroides (Bac), Bifidobacterium (Bif). Averages across volunteers are shown.

Figure 3

Changes through time of the first three principal components summarising variation in short chain fatty acids (SCFAs) log(concentrations). Black = control; green = inulin; pink = pectin. Solid = control antibiotics; dashed=gentamicin; dotted = ampicillin. The loadings and % variation for each principal component are shown in right-hand panels. Principal component 1 (PC1) represents production of all SCFAs except caproate. Principal component 2 (PC2) represents increasing concentration of SCFAs of longer chain length. Principal component 3 (PC3) represents proportionately increased concentration of BCFAs relative to acetate and caproate.