Microbiota-derived indole differentially shapes Entamoeba histolytica physiology and promotes host-compatible...

Area of Science:

• Microbiology
• Parasitology
• Host-Pathogen Interactions

Background:

• Entamoeba histolytica causes amoebiasis, colonizing the human gut where it encounters microbiota metabolites like indole.
• Previous work showed bacterial metabolites influence parasite virulence and stress responses.

Purpose of the Study:

• To investigate how acute versus long-term indole exposure affects E. histolytica physiology and host interactions.
• To understand the adaptive mechanisms of E. histolytica to indole in its natural gut environment.

Main Methods:

• Trophozoites were adapted to indole over two months.
• Proteomic profiling compared untreated, acutely exposed, and adapted parasites.
• Functional assays assessed cytoskeletal organization, motility, oxidative stress survival, and in vitro/in vivo colonization.
• Host inflammatory markers (CXCL1, lipocalin) were measured.

Main Results:

• Acute indole exposure inhibited growth and increased cytopathic activity.
• Indole-adapted parasites (ADI) showed smaller size, increased F-actin, enhanced migration, and reduced cytopathic activity.
• ADI trophozoites exhibited improved oxidative stress survival and more efficient cecum colonization in mice.
• Acutely exposed parasites induced stronger host inflammatory responses than ADI parasites.

Conclusions:

• Indole acts as an ecological cue, initially challenging E. histolytica.
• Sustained indole exposure induces adaptive reprogramming, enhancing stress tolerance and host-compatible colonization.
• Indole adaptation modulates E. histolytica's interaction with the host immune system.