Antibiotics are known for their capacity to perturb the structure of the gut microbiome, with subsequent complications that go beyond the gastrointestinal tract.
How host and gut microbiome-related factors modulate antibiotic susceptibility, however, is poorly understood.
As a result, scientists still struggle to understand why some gut bacteria are sensitive to antibiotics while a fraction of them survive treatment.
New research in mice, led by Dr. Peter Belenky from Brown University (USA), reveals that gut microbial metabolism alongside diet play a key role in modifying the extent of gut microbiome disruption in response to antibiotics.
The researchers used a combined metagenomic and metatranscriptomic approach to study the impact of three classes of antibiotics (amoxicillin, ciprofloxacin and doxycycline) on the gut microbiome’s metabolic response.
Amoxicillin led to a reduction in nearly all species, with the exception of members belonging to the Bacteroides genus. In contrast, both doxycycline and ciprofloxacin reduced the abundance of Bacteroides while increasing Firmicutes.
Beyond changes in the taxonomic structure, an overall decrease in the gut microbiota’s metabolic gene expression was observed at the community level.
At single-species level, Bacteroides thetaiotaomicron—which differ from other gut commensals by using alternative electron acceptors to ferment substrates—showed a notable increase secondary to amoxicillin administration. This was accompanied by an upregulation of genes involved in stress responses and sporulation and polysaccharide utilization, and a decrease in hexose utilization genes.
The researchers also examined how varying concentrations of glucose in diet affected cecal glucose and gut microbiome composition in mice after antibiotics administration. Amoxicillin (but not ciprofloxacin) treatment led to a fall in cecal glucose concentrations and this, in turn, may provide a unique gut environment that allows B. thetaiotaomicron to survive and expand.
Subsequent in vitro experiments were performed to further explore the effects of the gut microbiome’s use of carbon sources in response to antibiotics. The susceptibility of B. thetaiotaomicron and B. fragilis to amoxicillin in cultures was elevated by glucose, whereas fiber administration led to higher amounts of the antibiotic needed to kill the bacterium. That is, fiber intake protected B. thetaiotaomicron from amoxicillin when compared with glucose alone.
The higher susceptibility of B. thetaiotaomicron to amoxicillin in the presence of glucose was also confirmed in vivo. Dietary supplementation with glucose led to a reduced expansion of this gut bacterium following treatment with amoxicillin.
On the whole, these findings show that the availability of diet-based carbon sources that are used by the gut microbiome can influence the detrimental effects of antibiotics on gut microbial communities. As such, these results highlight the relevance of further research into the role of host diet and metabolic state in the development of antibiotic-induced imbalances in the gut microbiome.
Cabral DJ, Penumutchu S, Reinhart EM, et al. Microbial metabolism modulates antibiotic susceptibility within the murine gut microbiome. Cell Metab. 2019. doi: 10.1016/j.cmet.2019.08.020.
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