In the present double-blind, randomised, parallel intervention study, the effects of the intake of galacto-oligosaccharides (GOS) on the gut microbiota of twelve healthy adult subjects (aged 18–45 ...years with a normal BMI (18–25 kg/m2)) receiving amoxicillin (AMX) treatment were determined. All the subjects were treated with AMX (375 mg; three times per d) for 5 d and given either GOS (n 6) or placebo (maltodextrin, n 6) (2·5 g; three times per d) during and 7 d after AMX treatment. Faecal samples were collected twice before starting the treatment and on days 2, 5, 8, 12, 19 and 26. Due to AMX treatment, a decrease in the abundance of Bifidobacterium spp., an overgrowth of Enterobacteriaceae, and a disruption of the metabolic activity of the microbiota (increase in succinate, monosaccharide and oligosaccharide levels in the faecal samples) were observed in both groups (P< 0·05). Positive effects of GOS intake were observed on the levels of bifidobacteria, although not found to be significant. Data revealed that the levels of bifidobacteria were higher upon GOS intake than upon placebo intake, especially after AMX treatment. The activity of bifidobacteria and subsequent cross-feeding activity of the microbiota upon GOS intake compared with those upon placebo intake were reflected by the significant increase in butyrate levels (P< 0·05) in the faecal samples after AMX treatment. Despite the small number of subjects, our findings confirm previous results obtained in vitro, namely that GOS intake supports the recovery of the beneficial bifidobacteria and, indirectly, the production of butyrate after AMX treatment.
Antibiotic treatments can lead to a disruption of the human microbiota. In this in-vitro study, the impact of antibiotics on adult intestinal microbiota was monitored in a new high-throughput ...approach: a fermentation screening-platform was coupled with a phylogenetic microarray analysis (Intestinal-chip). Fecal inoculum from healthy adults was exposed in a fermentation screening-platform to seven widely-used antibiotics during 24h in-vitro fermentation and the microbiota composition was subsequently determined with the Intestinal-chip.
Phylogenetic microarray analysis was first verified to be reliable with respect to variations in the total number of bacteria and presence of dead (or inactive) cells. Intestinal-chip analysis was then used to identify and compare shifts in the intestinal microbial composition after exposure to low and high dose (1μgml−1 and 10μgml−1) antibiotics. Observed shifts on family, genus and species level were both antibiotic and dose dependent. Stronger changes in microbiota composition were observed with higher doses. Shifts mainly concerned the bacterial groups Bacteroides, Bifidobacterium, Clostridium, Enterobacteriaceae, and Lactobacillus. Within bacterial groups, specific antibiotics were shown to differentially impact related species.
The combination of the in-vitro fermentation screening platform with the phylogenetic microarray read-outs has shown to be reliable to simultaneously analyze the effects of several antibiotics on intestinal microbiota.
► Fermentation screening-platform successfully coupled to a microarray analysis ► Microarray provides reliable in-sights on antibiotic impact on the microbiota. ► Seven widely-used antibiotics affect adult intestinal microbiota differently. ► Even sub-MIC dose of antibiotics alters the microbiota composition.
In order to elaborate on the impact of amoxicillin treatment on the in vitro fermentation of specific structures of galacto-oligosaccharides (GOS), GOS was fractionated based on its degree of ...polymerization (DP) and the fermentation of individual DPs was studied. Different DP fractions of GOS and different isomeric structure within a DP fraction were preferentially degraded depending on the treatment applied to the microbiota. For the non-treated microbiota, the small DP fractions (dimers and trimers) were preferentially degraded as compared to the large DP fractions (tetramers till hexamers). β-d-Gal-(1→4/6)-d-Glc and β-d-Gal-(1→4)-β-d-Gal-(1→4)-d-Glc were the isomeric structures preferentially degraded within the DP2 and DP3 fraction, respectively. The fermentation of each size-fraction induced the production of various short chain fatty acids and the growth of several species of bifidobacteria. For amoxicillin-treated microbiota, the large size-fractions of GOS were preferentially degraded as compared to the small fractions. β-d-Gal-(1→4)-d-Gal and β-d-Gal-(1→4)-β-d-Gal-(1→3)-d-Glc were the isomeric structures preferentially degraded within the DP2 and DP3 fraction, respectively. Butyrate was only produced upon the fermentation of the large size-fractions. The differences in metabolic pattern of GOS depending on the treatment applied correlated with the changes in the microbiota composition, especially the growth of bifidobacteria. These results suggest that GOS, especially its large size-fractions, support the recovery of bifidobacteria and butyrate-producing bacteria after a treatment of the microbiota with amoxicillin.
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•The fermentation pattern of GOS is influenced by amoxicillin.•Large structures of GOS are preferentially fermented upon amoxicillin treatment.•Large structures of GOS induce butyrate production upon amoxicillin treatment.•All GOS size-fractions stimulate Bifidobacterium longum after amoxicillin treatment.
Abstract
Prebiotics are considered to have potential to reduce disturbances in the gut microbiota induced by antibiotics. Results in literature are, however, not consistent. The current in vitro ...study conducted in a fermentation screening platform allowed to unambiguously compare the impact of galacto-oligosaccharides (GOS) on adult gut microbiota composition and activity upon treatment with four antibiotics at two doses. The changes in relative abundance of bacteria upon antibiotic treatment and the growth of Bifidobacterium and Lactobacillus upon GOS addition were antibiotic and dose dependant. This conclusion explains discrepancies in literature and indicates that particular combinations of GOS antibiotic should be studied. The combination GOS–Amoxicillin was especially of interest as, after decrease in Bifidobacterium levels, a recovery of mainly Bifidobacterium longum was observed and could be correlated with specific degradation patterns of GOS. Next to different degradation profiles of individual GOS, an accumulation of monosaccharides and intermediate organic acids was observed in antibiotic-treated microbiota as compared to nontreated microbiota. This showed that although GOS were utilized and beneficial bacteria could grow in 3 of 4 antibiotics tested, the metabolic activity of an antibiotic-treated microbiota was still disturbed as compared to the nontreated microbiota.