The prevalence of gastrointestinal (GI) disorders, such as inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), poses significant global challenges and substantially burdens public health and the economy worldwide. IBD affects ~6.8 million and IBS ~780 million individuals globally. Mucosal-associated biofilms are highly prevalent in the GI tracts of IBS and IBD patients. These biofilms are associated a shifting gut microbiota composition toward a dysbiotic state. Preliminary clinical work in removing these biofilms through endoscopic jet washes appears to reduce the functional GI symptoms experienced by the patients. No pharmaceutical interventions exist or are in clinical development for non-invasive removal or inhibition targeting such GI biofilms. Hence, there is an unmet need to develop oral therapeutics to target biofilms associated with gut disorders.

Antimicrobial peptides (AMPs), identified in various animals and humans, effectively defend against bacteria. We aim to explore other AMPs to develop oral therapeutics for biofilm-associated GI diseases. We selected some AMP candidates by reviewing the literature and specific AMP databases. We synthesised the peptides by solid-phase peptide synthesis and screened them to assess their antimicrobial and antibiofilm properties. We have successfully synthesised, purified 30 AMPs and screened 12  from various organisms (amphibians, marsupials, and insects) for antimicrobial and antibiofilm activity against our literature-control strains Staphyloccocus aureus and Pseudomonas aeruginosa, and against two biofilm-positive patient isolates of Streptococcus parasanguinis and Escherichia coli. Ongoing efforts involve investigating the other AMPs, expanding to additional clinically isolated GI biofilm-producing strains, conducting structure-activity relationship studies of identified leads, and improving their gut-stability for oral administration. We aim to assess the toxicity of these AMPs early on using haemolytic and cytotoxicity assays and make necessary modifications and conjugations to enhance their therapeutic window and biofilm specificity. These advancements are crucial for their potential application in treating biofilm-positive patients with GI diseases.