Without dysbiosis
Nanoparticles with an antibiotic prevent the development of intestinal dysbiosis
Ekaterina Gugueva, PCR.news
Oral antibiotics have a detrimental effect on the intestinal microflora. The search for such a formula that would minimize damage to the microflora has been going on for a long time. The authors of a new study published in Nature Biomedical Engineering (Zhang et al., Glucosylated nanoparticles for the oral delivery of antibiotics to the proximal small intestine protect mice from gut dysbiosis) suggest packaging the drug in glycosylated nanoparticles.
The experiments were conducted on mice. At the first stage, scientists using RNA sequencing showed that the expression level of glucose transporter genes GLUT2 and SGLT1 is much higher in the small intestine than in the large intestine. Consequently, the absorption of glucose and glycosylated molecules in the small intestine is more efficient. The number of microorganisms in the large intestine significantly exceeds that in the small intestine. This means that the absorption of the antibiotic in the small intestine will save most of the microbiota.
Scientists have constructed polymer nanoparticles cross-linked with glucose residues. To facilitate their penetration through the mucus layer covering the intestinal epithelium, positively charged lipid groups were added to the formula. The scientists tested four variants of nanoparticles: NP (nanoparticles without glucose residues and lipid groups), GNP (nanoparticles with glucose residues), PNP (positively charged nanoparticles), PGNP (positively charged nanoparticles with glucose residues). Mice were injected with particles into the stomach.
PGNP was absorbed faster than other particles in the small intestine. It was in the epithelium of the small intestine that their greatest concentration was observed. The amount of PGNP particles in the faeces was lower compared to the other variants, and their concentration in the blood was higher. Consequently, their absorption was most effective.
At the next stage, the scientists determined the absorption efficiency of the antibiotic associated with nanoparticles. The experiments were carried out using ampicillin. In mice that received PGNPs-Amp, the concentration of the antibiotic in the blood after four hours was 20.9 times higher than in those who were injected with the drug without particles, and the concentration of ampicillin in feces was reduced. This indicates increased absorption of the antibiotic in the composition of PGNP.
Next, the scientists evaluated the effectiveness of PGNPs-Amp in comparison with free ampicillin. To do this, they used a mouse model of a lung infection caused by Streptococcus pneumoniae. It turned out that the antibiotic associated with particles copes much better with infection. Pathoanatomic and histological studies have shown a decrease in the inflammatory response and a decrease in the degree of damage to lung tissue. In addition, the antibiotic in the composition of PGNP did not induce dysbiosis: the microbiota suffered less than from a free antibiotic and recovered faster.
Some metabolic disorders, such as obesity and type 2 diabetes mellitus, are associated with intestinal dysbiosis. Scientists have confirmed that the introduction of a free antibiotic contributes to an increase in the body weight of mice and a violation of glucose tolerance. But the introduction of PGNP with an antibiotic did not lead to a significant change in these indicators. Microbiota disorders also contribute to the increased susceptibility of the body to pathogenic bacteria. Mice treated with PGNP with an antibiotic for five days were less sensitive to the pathogenic bacterium Citrobacter rodentium than mice given free antibiotics.
Finally, using metagenomic sequencing of stool samples, the authors showed that PGNPs-Amp, unlike free ampicillin, does not contribute to the accumulation of antibiotic resistance genes in the intestinal bacterial community. According to the authors, the formulation of antibiotics with PGNP is a promising approach that allows them to be taken in the usual way, but reduces the likelihood of side effects.
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