Indole toxicity on removal of uremic toxin p-cresol, in-vitro study of Thauera aminoaromatica S2

Protein-bound uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, are major contributors to chronic kidney disease (CKD) complications and are poorly removed by dialysis due to strong albumin binding. Targeting their gut-derived microbial precursors offers a promising strategy to reduce systemic toxin load. Thauera aminoaromatica S2 is known to anaerobically degrade p-cresol, but its response to indole and its potential as an orally administered microbial therapy remain poorly characterized. Here, we investigated the activity of Thauera aminoaromatica S2 under exposure to both p-cresol and indole in planktonic and hydrogel-encapsulated forms. Low indole levels (0.25 mM) enhanced planktonic growth in the presence of 2 mM p-cresol, whereas co exposure inhibited p-cresol degradation in hydrogel systems, likely due to restricted diffusion and elevated local indole concentrations. Nonetheless, encapsulation enabled tolerance to conditions (2 mM p-cresol + 0.5 mM indole) that abolished planktonic growth, suggesting microenvironmental protection. Incorporation of activated carbon into the hydrogel restored p-cresol removal despite indole exposure, likely through localized indole sequestration. These results highlight the potential of combining encapsulation with adsorptive additives to stabilize microbial function and support the development of microbial therapies aimed at mitigating uremic toxin precursors in CKD.