Bioactive small molecules produced by the human gut microbiome modulate Vibrio cholerae sessile and planktonic lifestyles

Abstract

Humans live in symbiosis with a diverse community of microorganisms, which has evolved to carry out many specific tasks that benefit the host, including protection against invading pathogens. Within the chemical diversity of the gastrointestinal tract, small molecules likely constitute chemical cues for the communication between the microbiota and pathogens. Therefore, we sought to investigate if molecules produced by the human gut microbiota show biological activity against the human pathogen Vibrio cholerae. To probe the effects of the gut metabolome on V. cholerae, we investigated its response to small-molecule extracts from human feces, from a complex bacterial community cultivated in vitro, and from culture supernatants of Enterocloster citroniae, Bacteroides thetaiotaomicron, and Bacteroides vulgatus. Using RNA sequencing, we determined the impact of the human gut metabolome on V. cholerae global gene expression. Among the genes downregulated in the presence of the fecal extract, the most overrepresented functional category was cell motility, which accounted for 39% of repressed genes. Repression of V. cholerae motility by the fecal extract was confirmed phenotypically, and E. citroniae extracts reproduced this phenotype. A complex in vitro microbial community led to increased motility, as did extracts from B. vulgatus, a species present in this community. Accordingly, mucin penetration was also repressed by fecal and E. citroniae extracts, suggesting that the phenotypes observed may have implications for host colonization. Together with previous studies, this work shows that small molecules from the gut metabolome may have a widespread, significant impact on microbe-microbe interactions established in the gut environment.

Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases

“…Metabolite produced by gut microbiota also plays an important role in the resistance of V. cholerae. Bioactive compounds generated by gut microbiota impede V. cholerae motility and its ability to penetrate mucin [108]. Colibactin, a genotoxin generated by Escherichia coli, could inhibit the colonization of V. cholerae and is associated with the better prognosis of cholera patients [109].…”

Crosstalk between gut microbiota and renal ischemia/reperfusion injury

“…Studies have confirmed that the body’s homeostasis and the intestinal immune function depend on the balance of bacteria in different degrees, and once this balance is destroyed, it will lead to the occurrence of related diseases ( Bruellman and Llorente, 2021 ; Han et al., 2021 ; Khan et al., 2021 ; Shute et al., 2021 ; Sun et al., 2021 ; Deng et al., 2022b ; Hu et al., 2022 ). The dysregulation of gut microbiota can be caused by many factors, such as age ( Du et al., 2021 ; Janiak et al., 2021 ), lifestyle ( Pauer et al., 2021 ; Shin et al., 2021 ), dietary habits ( Neumann et al., 2021 ; Tap et al., 2021 ; Yu et al., 2021 ), immunity ( Foley et al., 2021 ; Hosseinkhani et al., 2021 ) and the use of antibiotics ( Kang et al., 2021 ; Mcdonnell et al., 2021 ; Strati et al., 2021 ; Vicentini et al., 2021 ).…”

Anti-biofilm and anti-virulence potential of cell free supernatant of Akkermansia muciniphila against Salmonella

“…Microbiota-mediated resistance against pathogenic bacteria occurs through indirect or direct mechanisms, such as nutrient or niche competition and antimicrobial compound production [6][7][8] . More importantly, various studies have explored that molecules produced by gut microbiota or metabolites derived from specific microbiota members could mitigate pathogens' virulence, protect mice from infection induced by enteric pathogens and restore the native community after the disruption with antibiotics [7,[9][10][11] .…”