Saturday, October 30, 2021

Precision antibiotics

Antibiotics can effectively eliminate infection-causing bacteria, but they also perturb microbial communities in the body and this perturbation can be irreversible, depending on the individual. A new study demonstrates that the pre-treatment baseline gut microbiota is a major determinant of whether there will be complete or partial recovery, 

antibiotics microbiome perturbations
or whether antibiotics will shift microbiome to completely new states with little resemblance to the baseline community. This is consistent with the role of pre-treatment microbiota in determining response to fecal microbiota transplantation (FMT) and dietary interventions.

New research suggests a strong predictive role for baseline microbiota, especially when antibiotic exposure is less intense. Typically, after antibiotic-induced perturbations, composition of the gut microbiome changes from the baseline (phase 1) followed by post-antibiotic reorganization (phase 2) (original figure) - that will either bring the microbiome back to its initial state, change it slightly or change it dramatically creating a completely new microbiome. The latter is usually called a “regime shift”. A resistant community always resists perturbation, while a resilient community is able to completely recover and stabilize into a fully functional state after antibiotic treatment. 

Principal component mixed effect regression using microbiota and granular antibiotic exposure data showed that microbiota departures from baseline depend on the composition of the pre-treatment microbiota. Penalized generalized estimating equations identified 6 taxa within pre-treatment microbiota that predicted the extent of antibiotic-induced perturbations.

In the final model, 5 baseline taxa (RoseburiaBlautiaEggerthella, a Lachnospiraceae genus, and a Clostridiales genus) predicted larger microbiota departures from baseline, and one taxon (Bacteroides) predicted larger resistance to perturbations. 

Specific Roseburia species degrade dietary fiber ╬▓-mannan, producing short-chain fatty acids such as butyrate, with numerous and profound homeostatic effects. Similarly, certain Eggerthella species have significant metabolic potential, contributing, for example, to the conversion of dietary fiber-derived lignans to bioactive compounds Antimicrobial peptides produced by certain Blautia species have been shown to confer colonization resistance against antibiotic-resistant pathogens Bacteroides might be exhibiting stabilizing effect via quorum sensing or by secreting antimicrobial compounds such as propionate.  Bacteroides fragilis has a protective effect on functional gastrointestinal disorders that are thought of as disorders of homeostatic imbalance

Next-generation precision antibiotics should be specific towards particular pathogens and their genes. They also should be tailored to the baseline host microbiome to prevent the development of functional gastrointestinal disorders. 

REFERENCES

Rashidi, A., Ebadi, M., Rehman, T.U. et al. Gut microbiota response to antibiotics is personalized and depends on baseline microbiota. Microbiome 9, 211 (2021). https://doi.org/10.1186/s40168-021-01170-2

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