Authors: Rajendra Prasad Janapatla, Anna Dudek, Chyi-Liang Chen, Chih-Hsien Chuang, Kun-Yi Chien, Ye Feng, Yuan-Ming Yeh, Yi-Hsin Wang, Hsin-Ju Chang, Yuan-Chuan Lee, Cheng-Hsun Chiu
Published: 2023-02-02
DOI: 10.1186/s12929-023-00902-w
Source: Full article
AbstractBackgroundPseudomonas aeruginosaintestinal carriage rates are significantly higher in immunosuppressed individuals and hospitalized patients who therefore have increased risk of infections and antibiotic-associated diarrhea. To combat intestinal dysbiosis and decolonizeP. aeruginosafrom gastrointestinal tract, we investigated the anti-adherence and gut microbiota modulation properties of marine prebiotic fucoidans.MethodsProteomic analysis of culture supernatant was performed by LC–MS/MS. Using lectin-based enzyme-linked immunosorbent assay, hemagglutinin domain interaction and inhibition with biomolecules were studied. We investigated the role of nutritional grade fucoidans in a mouse model and used 16S ribosomal RNA sequencing to examine fecal microbiota composition.ResultsAnalysis of culture supernatant proteins indicated the secretion of two-partner secretion (TPS) family proteins, including TpsA1/CdiA2 and TpsA2/CdiA1. Lectin like activity at the N-terminal of TpsA due to a conserved hemagglutinin domain (Pfam identifier [ID] PF05860) mediates binding to mucins that carry multiple fucosylated glycans. Fucose-rich sulfated polysaccharides (fucoidans) and sulfated dextrans were found to be potent inhibitors of the recombinant N-terminal hemagglutinin domain of TpsA (TpsA-NT-HAD) binding to mucins. In a mouse model, antibiotic-induced dysbiosis was essential forP. aeruginosagastrointestinal colonization. After prophylactic oral fucoidans supplementation, a higher proportion (60%) of the mice were decolonized over time and resisted re-colonization, this was associated with remarkable expansion ofBacteroides(post-infection day-3 abundance, 29–50%) and consequential reductions in bloom ofEnterobacteriaceaeandEnterococcaceaepopulations. In the non-supplemented group,Parabacteroidesmediated recovery from dysbiosis but failed to decolonizeP. aeruginosa.ConclusionsSupplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization ofP. aeruginosafrom gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficialBacteroidespopulation. We suggest the prophylactic use of nutritional grade fucoidans to decolonizeP. aeruginosafrom gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizingP. aeruginosa.