Drivers of Clostridioides difficile hypervirulent ribotype 027 spore germination, vegetative cell growth and toxin production in vitro

Abstract

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Negative interactions determine Clostridioides difficile growth in synthetic human gut communities

“…We showed that communities that reduce the external pH below 6.2 inhibit C. difficile in a pH‐dependent manner, consistent with studies showing that C. difficile has lower viability and rates of sporulation in acidic environments (Wetzel & McBride, 2020; Yuille et␣al , 2020). We note that our in␣vitro system differs from the human gut, lacking the pH‐buffering secretion of bicarbonate by host intestinal epithelial cells.…”

“…For example, communities with the same richness invaded with equal abundances of C. difficile showed a wide range of C. difficile abundances at 48 h (Fig 2A). Since environmental pH has been shown to influence C. difficile ’s growth in previous studies (Wetzel & McBride, 2020; Yuille et␣al , 2020), we turned next to investigate how biotic modification of the environment alters the growth of C. difficile . To this end, we grew the set of 15 3–4 member communities for 6 h before invading with low or high initial densities of C. difficile to give the communities time to modify the environment.…”

Species richness determinesC. difficileinvasion outcome in synthetic human gut communities

“…Our results demonstrated that communities can inhibit growth of C. difficile by acidifying the environment. We showed that communities that reduce the external pH below 6.2 inhibit C. difficile in a pH-dependent manner, consistent with studies showing that C. difficile has lower viability and rates of sporulation in acidic environments 33,34 . While our in vitro system lacks the pH-buffering secretion of bicarbonate by host intestinal epithelial cells, the amount of bicarbonate buffer in our media (4.8 mM) is within the estimated range in the gastrointestinal tract (2-20mM) 45 , suggesting the observed pH changes in our media could be physiologically relevant.…”

“…2a). Since environmental pH has been shown to influence C. difficile's growth in previous studies 33,34 , we turned next to investigate how biotic modification of the environment alters the growth of C. difficile. To this end, we grew the set of 15, 3-4 member communities for six hours and then invaded with low or high initial densities of C. difficile.…”

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites

“…They affect host physiology, including an energy source for colon cells, regulating the intestinal barrier, and affecting inflammatory responses ( Correa-Oliveira et al, 2016 ). SCFAs also inhibit C. difficile toxin production ( Yuille et al, 2020 ), reducing CDI ( McDonald et al, 2018a ; Fachi et al, 2020 ) and inhibiting spore growth ( Battaglioli et al, 2018 ; Hryckowian et al, 2018 ; Neumann-Schaal et al, 2019 ). Like previous studies ( McDonald et al, 2018a ), the CDI group showed decreased butyric acid, propionic acid, acetic acid, and A. muciniphila restored SCFA metabolism, possibly by restoring the intestinal flora balance.…”