The intestinal tract routinely undergoes a variety of injuries due to disease or direct surgical manipulation.

The process by which successful repair and return of function occurs following these insults is highly dependent on the composition and function of the intestinal microbiota.

Consequently, wound healing and repair of the intestinal tract is complex due to the presence of intestinal microbiota, which can either enhance or severely impair healing.

Iatrogenic injury, such as that which occurs when gastroenterologists remove intestinal tumors via endoscopy or major surgical resection, often disrupt the normal microbiome leaving a large wound to heal in the presence of highly pathogenic bacteria.

These curative surgical interventions are often complicated by excessive scar formation, stricture, stenosis, or grossly inadequate healing.

Use of antibiotics and application of surgical techniques to remove tumors or diseased intestinal tissue creates local environmental cues that shift the composition, community structure, and function of the normal microbiota such that certain strains proliferate and predominate.

These pathogens can become multidrug resistant as the promiscuous use of antibiotics remains a problem.

Thus, there is a pressing need to develop therapeutic compounds that do not disrupt the normal intestinal microbial community structure as normal flora protect against overgrowth and invasion of pathogens by suppressing key virulence traits.

Phosphate becomes depleted in the intestinal tract following surgical injury and is a major “cue” that triggers bacterial virulence as pathogens scavenge phosphates from host tissues leading to intestinal mucus disruption.

Studies indicate that phosphate replenishment prevents in vitro P. aeruginosa virulence expression while maintaining bacterial survival.

Oral administration of inorganic phosphate, however, is prone to loss of bioavailability in the colon, and is rapidly absorbed in the small intestine necessitating administration of high concentrations of orally administered phosphates which may impair kidney function.

To address these barriers, we have developed a nanoparticle fabrication process for synthesis of hydrogel nanoparticles encapsulated with monophosphate (Pi) and polyphosphate (PPi), NP-Pi and NP-PPi, respectively, enabling sustained release of phosphates.

Importantly, our published findings indicate that NP-PPi attenuate P. aeruginosa virulent phenotype expression (pyoverdine and pyocyanin production) in vitro in a dose-dependent manner while maintaining bacterial survival.

Our recent published findings also indicate that a combination treatment of NP-Pi and NP-PPi is required to attenuate increased bacterial collagenase expression and biofilm formation, key phenotypes involved in degradation of intestinal collagen and healing impairment, across gram-positive (E. faecalis) and gram-negative (S. marcescens and P. aeruginosa) pathogens.

Our findings suggest that sustained release of different forms of phosphate confers in vitro protection against gram-positive and gram-negative pathogens, thereby providing a broad-spectrum treatment for attenuation of tissue-disruptive bacterial phenotypes without eradicating protective flora over the course of intestinal healing.