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Biology subjects

Godfrey, B. J.

Publications and source records attributed to Godfrey, B. J..

3 recordsLinked to original sources

Development of a Stabilized Alginate-based Hydrogel for Oral Delivery of Encapsulated Live Cultures and Allowing their Intact Passage Through the Digestive System.

Alginate hydrogels are widely used for biocompatible encapsulation due to their low cost, mild gelation conditions, and scalability; however, their limited mechanical strength and poor chemical stability under physiological conditions restrict their utility for oral delivery applications. In particular, the development of robust alginate formulations capable of surviving gastrointestinal salt and pH exposures is critical for advancing encapsulated microbial therapeutics for chronic kidney disease (CKD). In this study, we investigated the incorporation of ferric iron into calcium alginate networks as a strategy to enhance gel stability while maintaining biocompatibility. Using a three-ion competition approach, we achieved controlled introduction of ferric ions into calcium alginate gels without significantly altering bulk mechanical properties relative to standard calcium alginate. Although the initial ferric-containing gels displayed comparable modulus and structure, post-treatment with chitosan under mildly acidic conditions produced a dramatic increase in gel stability in physiological salt concentrations across both acidic and neutral pH environments. Ferric-containing gels formed at pH 4.6 absorbed negligible chitosan, in contrast to iron-free alginate gels, which incorporated substantial chitosan under identical conditions. These results support the formation of a thin, dense interfacial complex between chitosan, ferric ions, and alginate at the gel surface, which reinforces the matrix and inhibits dissolution. The resulting hybrid ferric-calcium alginate formulation enabled the production of sub-millimeter beads capable of encapsulating live Thauera aminoaromatica while preserving anaerobic p-cresol degradation activity at 37 {degrees}C using nitrate as an electron acceptor. Collectively, these findings establish ferric-modified alginate hydrogels as a promising, scalable platform for stable oral delivery of encapsulated microbial therapeutics.

bioengineering↗

Biochemical mechanism of p-cresol removal by Thauera aminoaromatica S2

Protein-bound uremic toxins are inefficiently cleared by dialysis and contribute to complications in chronic kidney disease, motivating approaches that target their gut-derived precursors. Here we investigate anaerobic p-cresol metabolism by the environmental denitrifier Thauera aminoaromatica S2, a pathway originally evolved for aromatic pollutant degradation. Proteomic stable isotope probing with 13C-labeled p-cresol reveals strong incorporation of labeled carbon into T. aminoaromatica proteins, whereas parallel incubations with human fecal microbiomes show minimal incorporation, indicating limited intrinsic gut capacity for p-cresol utilization. Label-enriched proteins enable reconstruction of the anaerobic p-cresol degradation pathway and identification of key enzymes synthesized during growth on p-cresol. Moreover, hydrogel-encapsulated T. aminoaromatica remains active during co-incubation with the gut microbiome, achieving complete removal of 0.3 mM p-cresol in less than 10 hours, a timescale compatible with typical intestinal transit in the colon. Together, these findings establish a biochemical basis for repurposing environmental aromatic degradation pathways for gut-localized p-cresol removal.

bioengineering↗

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.

microbiology↗