The Effect of Short-Chain Fatty Acids on Growth of Cryptosporidium parvum In Vitro
2022
Keelaghan, Aidan P. | Charania, Raheela | Mead, Jan R.
In a previous study, we observed an increase in the severity of cryptosporidial infection corresponding to decreased levels of short-chain fatty acids (SCFAs). Therefore, we decided to examine the effect of SCFAs on Cryptosporidium growth in human ileocecal adenocarcinoma (HTC-8) cells. HTC-8 cells were infected with 1 × 10⁵ C. parvum oocysts. After 48 h of incubation with selected SCFAs, cells were fixed and labeled with monoclonal antibody directed to all intracellular stages, and the number of parasites was quantitated using a fluorescent microscope. Acetate, butyrate, propionate and valproate significantly inhibited growth, with an EC₅₀ between 4 and 10 mM. Additionally, when combined, butyrate, acetate and propionate showed increased efficacy. Butyrate also inhibited growth when incubated with sporozoites prior to infection of host cell monolayers. In addition, we looked at possible mechanisms of action of inhibition. A combination of C. parvum infection and butyrate treatment led to increases in apoptosis and certain inflammatory cytokines. We conclude that acetate, propionate and butyrate have direct inhibitory activities in host cells against C. parvum, and butyrate can also affect sporozoite infectivity directly. While not preventing infection, SCFAs may help in keeping the infection low or in check.
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