Long-Term Lactulose Administration Improves Dysbiosis Induced by Antibiotic and <i>C. difficile</i> in the PathoGut<sup>TM</sup> SHIME Model

<i>Clostridioides difficile</i> infection (CDI) is the leading cause of antibiotic-associated diarrhea and an important nosocomial infection with different severity degrees. Disruption of the gut microbiota by broad-spectrum antibiotics creates a proper environment for <i>C. diffic...

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Main Authors: Marta Calatayud (Author), Cindy Duysburgh (Author), Pieter Van den Abbeele (Author), Dennis Franckenstein (Author), Angelika Kuchina-Koch (Author), Massimo Marzorati (Author)
Format: Book
Published: MDPI AG, 2022-10-01T00:00:00Z.
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Summary:<i>Clostridioides difficile</i> infection (CDI) is the leading cause of antibiotic-associated diarrhea and an important nosocomial infection with different severity degrees. Disruption of the gut microbiota by broad-spectrum antibiotics creates a proper environment for <i>C. difficile</i> colonization, proliferation, and clinical disease onset. Restoration of the gut microbial ecosystem through prebiotic interventions can constitute an effective complementary treatment of CDI. Using an adapted simulator of the human gut microbial ecosystem, the PathoGut<sup>TM</sup> SHIME, the effect of different long-term and repeated dose lactulose treatments was tested on <i>C. difficile</i> germination and growth in antibiotic-induced dysbiotic gut microbiota environments. The results showed that lactulose reduced the growth of viable <i>C. difficile</i> cells following clindamycin treatment, shifted the antibiotic-induced dysbiotic microbial community, and stimulated the production of health-promoting metabolites (especially butyrate). Recovery of the gut microenvironment by long-term lactulose administration following CDI was also linked to lactate production, decrease in pH and modulation of bile salt metabolism. At a structural level, lactulose showed a significant bifidogenic potential and restored key commensal members of the gut ecosystem such as <i>Lactobacillaceae</i>, <i>Veillonellaceae</i> and <i>Lachnospiraceae</i>. These results support further human intervention studies aiming to validate the in vitro beneficial effects of lactulose on gut microbiome recovery during antibiotic exposure and CDI.
Item Description:10.3390/antibiotics11111464
2079-6382