Cocktail of eighteen commensal bacteria: a new weapon against antibiotic resistance?

Each year, during the World Antimicrobial Resistance Awareness Week, the WHO warns the public that the overuse of antibiotics promotes colonization of the gut by antibiotic-resistant pathogens. These pathogens include bacteria from the Enterobacteriaceae (sidenote: Enterobacteriaceae Enterobacteriaceae: family of gram-negative bacteria of the order Enterobacterales which includes the genera Escherichia and Klebsiella (two pathogens heavily implicated in antibiotic resistance), as well as Buttiauxella, Enterobacter, Gibbsiella, Salmonella, and Shigella, among others. Explore LPSN )  family, such as Escherichia coli and Klebsiella pneumoniae. These bacteria are responsible for severe infections, particularly in hospitals and among patients suffering from chronic inflammatory bowel diseases (IBD).

Now an alternative therapy is emerging in the fight against antibiotic resistance: commensal bacteria from the gut microbiota. Fecal microbiota transplantation appears to reduce the abundance of pathogenic Enterobacteriaceae, but the results have so far been mixed and have raised concerns about safety.

Hence the alternative presented in a study published in Nature ¹ : identify a combination of specific commensal bacteria capable of eliminating Enterobacteriaceae and determine their mode of action.

Winning combo of 18 strains

By analyzing stool samples from five healthy human donors, the researchers isolated 124 bacterial strains. Among the combinations tested, they identified a group of 18 synergistic strains, dubbed F18-mix, which significantly reduced the abundance of Klebsiella pneumoniae and Escherichia coli in germ-free mice (sidenote: Germ-free mice Germ-free mice: mice used in microbiota research that are bred in sterile environments and therefore free of microorganisms. They can be orally fed microbiota for studies under controlled conditions. ) .

F18-mix appears to specifically target Enterobacteriaceae without affecting other commensal bacteria, thus preserving the ecological balance in the gut while eliminating pathogens. 

The key to competition between F18-mix and Enterobacteriaceae appears to be access to carbon sources, and particularly gluconate. By depriving Enterobacteriaceae of this sugar essential to their growth, F18-mix gains the upper hand and prevents the former’s proliferation.

Towards a microbiotic therapy?

The researchers also tested the efficacy of F18-mix on a mouse model receiving microbiota from patients with Crohn’s disease or colitis. They observed not only a reduction in Enterobacteriaceae abundance, but also an increase in microbiota diversity. In colitis-susceptible mice, F18-mix even succeeded in reducing histological colitis scores and biomarkers of gut inflammation. 

This study paves the way for targeted microbiotic treatments against enterobacterial infections. Commensal flora may represent a promising alternative to antibiotics, limiting the emergence of resistance. However, these results came from controlled conditions in mouse models. Further studies will be required to demonstrate their applicability to humans.