Towards versatile, antibiotic-specific carbohydrate-formulations for decreasing antibiotics-use and side-effects

Summary

Despite its univocal success in fighting infectious diseases, antibiotic-use has to be drastically reduced in humans and livestock because of emerging multidrug-resistance. Here, we propose to accomplish this by enhancing intestinal health and defense by designing specific formulations of dietary-fibers for food and feed. This also prevents side-effects such as damage of antibiotics to microbiota and gut barrier-function. These efforts have to be done in an antibiotics-specific fashion as it is known that beneficial effects of dietary fibers for microbiota is antibiotic-type dependent. The focus will be on resistant starches (RS) including isomaltopolysaccharides and galacto-oligo-saccharides (GOS) for which the proof of principle of attenuation of antibiotics-induced intestinal-damage and reduction of antibiotics-use have been demonstrated. The hypothesis of the proposal is: specific combinations of RS and GOS can prevent and support recovery of mucosal microbiota and barrier function in an antibiotics-specific fashion and addition of these components to food and feed can prevent frequency of infectious diseases and antibiotics usage. RS and GOS will be synthesized in different chemical configurations and tested on (i) effects on human and pig fecal-microbiota under antibiotics exposure, (ii) modulation of epithelial barrier function in the presence and absence of model-pathogens and selected antibiotics, (iii) mucus production in presence and absence of infectious stressors and antibiotics, (iv) on immune-barrier function in complex co-cultures. Finally, (v) a proof of principle of rescuing effects on microbiota of a specific dietary-fiber (combination), after antibiotic treatment will be performed in a human pilot study.

Details

Project number

ALWCC.2017.002

Main applicant

Prof. dr. P. de Vos

Affiliated with

Rijksuniversiteit Groningen, Universitair Medisch Centrum Groningen, Pathologie

Duration

01/01/2018 to 31/12/2021