Impacto da deficiência em fibras dietéticas na infecção pulmonar causada por uma cepa de Klebsiella pneumoniae resistente a antimicrobianos

Abstract

According to the World Health Organization (WHO), it is estimated that approximately 10million people will die from infections caused by antimicrobial-resistant microorganisms(AMR) by the year 2050. While the importance of the intestinal microbiota to host health isrecognized, many studies have pointed to the intestinal microbiota as a reservoir ofantimicrobial resistance genes, known as the intestinal resistome. Industrialized diets lowin fiber content or lacking fiber result in imbalances in the diversity and function of theintestinal microbiota (dysbiosis), reducing the host's ability to resist infections caused bypathobiont microorganisms. Moreover, studies have shown that this industrialization cannegatively impact the intestinal resistome, leading to an increase in horizontal transfer ofresistance genes and consequently an increase in the diversity and abundance of thesegenes. In this context, we investigated the impact of a low-fiber diet on the resistome ofintestinal Enterobacteriaceae strains and evaluated the host's susceptibility to lunginfections caused by antimicrobial-resistant Klebsiella pneumoniae. Our findings suggestthat low-fiber diets induce alterations in the intestinal microbiota of C57BL/6 mice,increasing their susceptibility to lung infections by antimicrobial-resistant K. pneumoniae.Furthermore, fiber-deficient diets increase the frequency of Escherichia coli and K.pneumoniae with intermediate resistance phenotypes to the antibiotics streptomycin andciprofloxacin. Fifteen days after lung infection, we observed an increase in ampicillin-resistant Enterobacteriaceae in the intestinal microbiota. Interestingly, when performingfecal transplants to germ-free mice, we observed the same susceptibility profile to lunginfection by antimicrobial-resistant K. pneumoniae in those receiving feces fromconventionally fed C57BL/6 mice on low-fiber diets. Additionally, after infection of theseanimals, we also observed a reduction in propionate levels in the feces, along with anincrease in cultivable Enterobacteriaceae resistant to ampicillin, ceftriaxone, andciprofloxacin in the intestine, and an increase in the frequency of E. coli with intermediateresistance phenotypes to streptomycin and ciprofloxacin. In conclusion, these resultsreinforce the hypothesis that the intestinal microbiota is an important reservoir ofresistance genes, highlighting the fact that nutritional imbalance may favor the expansionof the resistome in the host following an infection by AMR bacteria. Understanding theintestinal resistome and the factors that impact its composition and structure is essentialfor developing strategies to control antimicrobial resistance.