Marine prebiotics mediate decolonization of Pseudomonas aeruginosa from gut by inhibiting secreted virulence factor interactions with mucins and enriching Bacteroides population

Journal of Biomedical Science

Research

Yuan-Ming Yeh¹  Yuan-Chuan Lee²  Chih-Hsien Chuang³  Kun-Yi Chien⁴  Ye Feng⁵  Hsin-Ju Chang⁶  Anna Dudek⁶  Chyi-Liang Chen⁶  Rajendra Prasad Janapatla⁶  Yi-Hsin Wang⁶  Cheng-Hsun Chiu⁷ 

[1] Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Department of Biology, Johns Hopkins University, Baltimore, MD, USA;Department of Pediatrics, St. Paul’s Hospital, Taoyuan, Taiwan;Graduate Institute of Biomedical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan;Institute for Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China;Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan;Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan;

关键词: Pseudomonas aeruginosa;    Two-partner secretion system;    Hemagglutinin;    Gastrointestinal colonization;    Microbiota;    Dysbiosis;    Prebiotics;    Fucoidans;   

DOI  :  10.1186/s12929-023-00902-w

 received in 2022-09-29, accepted in 2023-01-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPseudomonas aeruginosa intestinal 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 decolonize P. aeruginosa from 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 for P. aeruginosa gastrointestinal 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 of Bacteroides (post-infection day-3 abundance, 29–50%) and consequential reductions in bloom of Enterobacteriaceae and Enterococcaceae populations. In the non-supplemented group, Parabacteroides mediated recovery from dysbiosis but failed to decolonize P. aeruginosa.ConclusionsSupplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization of P. aeruginosa from gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficial Bacteroides population. We suggest the prophylactic use of nutritional grade fucoidans to decolonize P. aeruginosa from gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizing P. aeruginosa.

【 授权许可】

CC BY   
© The Author(s) 2023

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