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The Effect of Short-Chain Fatty Acids on Growth of Cryptosporidium parvum In Vitro
Aidan P Keelaghan1,2, Raheela Charania1,2, Jan R Mead1,2
1Department of Pediatrics, Emory University and Children's Healthcare Organization of Atlanta, Atlanta, GA 30322, USA.
Abstract:
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.
Insights
Short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate inhibit Cryptosporidium parvum growth in host cells. Butyrate also reduces sporozoite infectivity, potentially managing infections.
Area of Science:
- Parasitology
- Cell Biology
- Microbiology
Background:
- Cryptosporidial infection severity correlates with reduced short-chain fatty acid (SCFA) levels.
- SCFAs play a role in host-pathogen interactions and gut health.
Purpose of the Study:
- To investigate the direct impact of SCFAs on Cryptosporidium parvum growth in human intestinal cells.
- To explore the potential of SCFAs as a therapeutic strategy against cryptosporidiosis.
Main Methods:
- Human ileocecal adenocarcinoma (HTC-8) cells were infected with C. parvum oocysts.
- Cells were incubated with various SCFAs (acetate, butyrate, propionate, valproate) and parasite numbers quantified.
- Mechanisms of inhibition, including apoptosis and cytokine induction, were examined.
Main Results:
- Acetate, butyrate, propionate, and valproate significantly inhibited C. parvum growth (EC50: 4–10 mM).
- Combined SCFAs showed enhanced efficacy; butyrate also inhibited sporozoite infectivity.
- Butyrate treatment increased apoptosis and inflammatory cytokines in infected cells.
Conclusions:
- Acetate, propionate, and butyrate exhibit direct inhibitory effects on C. parvum within host cells.
- Butyrate possesses dual activity, inhibiting both intracellular parasites and extracellular sporozoites.
- SCFAs may serve as a supportive measure to control C. parvum infection levels.
